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Sample records for lesion activity assessment

  1. Optical Assessment of Caries Lesion Structure and Activity

    NASA Astrophysics Data System (ADS)

    Lee, Robert Chulsung

    New, more sophisticated diagnostic tools are needed for the detection and characterization of caries lesions in the early stages of development. It is not sufficient to simply detect caries lesions, methods are needed to assess the activity of the lesion and determine if chemical or surgical intervention is needed. Previous studies have demonstrated that polarization sensitive optical coherence tomography (PS-OCT) can be used to nondestructively image the subsurface lesion structure and measure the thickness of the highly mineralized surface zone. Other studies have demonstrated that the rate of dehydration can be correlated with the lesion activity and that the rate can be measured using optical methods. The main objective of this work was to test the hypothesis that optical methods can be used to assess lesion activity on tooth coronal and root surfaces. Simulated caries models were used to develop and validate an algorithm for detecting and measuring the highly mineralized surface layer using PS-OCT. This work confirmed that the algorithm was capable of estimating the thickness of the highly mineralized surface layer with high accuracy. Near-infrared (NIR) reflectance and thermal imaging methods were used to assess activity of caries lesions by measuring the state of lesion hydration. NIR reflectance imaging performed the best for artificial enamel and natural coronal caries lesion samples, particularly at wavelengths coincident with the water absorption band at 1460-nm. However, thermal imaging performed the best for artificial dentin and natural root caries lesion samples. These novel optical methods outperformed the conventional methods (ICDAS II) in accurately assessing lesion activity of natural coronal and root caries lesions. Infrared-based imaging methods have shown potential for in-vivo applications to objectively assess caries lesion activity in a single examination. It is likely that if future clinical trials are a success, this novel imaging

  2. How different do visuo-tactile criteria assess caries lesions activity status on occlusal surfaces?

    PubMed

    Floriano, I; Bonini, G C; Matos, R; Novaes, T F; Ekstrand, K R; Mendes, F M; Braga, M M

    2015-04-01

    We tested the association between active caries lesions assessed by two different criteria and clinical features of these caries lesions. Three examiners examined forty-nine 3- to 12-year-old children: one examiner used the Nyvad criteria, another examiner used the International Caries Detection and Assessment System with an additional criteria--Lesion Activity Assessment (ICDAS + LAA), and a reference examiner classified lesions regarding plaque stagnation, colour, lustre, cavities, depth and texture. Logistic regressions were used to test associations. For analyses, we grouped sound sites and inactive lesions vs active caries lesions, but also considering only inactive vs active lesions. Active lesions scored by both criteria were similarly associated with different clinical parameters tested, except when the sound sites were excluded from the analysis. In these cases, active lesions according to ICDAS + LAA were associated only with cavitation and texture. Texture was associated with divergences between criteria when differentiating sound or inactive lesions from active ones. Fewer divergences in differentiating active from inactive lesions were observed when lesions present lustre. Most clinical signs associated with active caries lesions were similar, but texture and severity tend to have a greater importance when using ICDAS + LAA for distinguishing caries activity status. Attention should be given to differences due to texture and lustre when using different indices. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Activity assessment of root caries lesions with thermal and near-IR imaging methods.

    PubMed

    Lee, Robert C; Darling, Cynthia L; Staninec, Michal; Ragadio, Antonio; Fried, Daniel

    2017-03-01

    The purpose of this study was to evaluate thermal and near-infrared (NIR) reflectance imaging methods for the assessment of the activity of root caries lesions. In addition, changes in the lesion structure were monitored with polarization sensitive optical coherence tomography (PS-OCT). Artificial bovine and natural root caries lesions were imaged with PS-OCT, and their dehydration rate was measured with thermal and NIR cameras. The lesion activity of the natural root caries samples was also assessed by two clinicians by conventional means according to ICDAS II guidelines. The thickness of the highly mineralized transparent surface layer measured using PS-OCT increased and the area enclosed by the time-temperature curve, ΔQ, measured with thermal imaging decreased significantly with longer periods of remineralization in simulated dentin lesions, but the NIR reflectance intensity differences, ΔI, failed to show any significant relationship with the degree of remineralization. The PS-OCT algorithm for the automated assessment of remineralization successfully detected the highly mineralized surface layer on both natural and simulated lesions. Thermal imaging provided the most accurate diagnosis of root caries lesion activity. These results demonstrate that thermal imaging and PS-OCT may be ideally suited for the nondestructive root caries lesion activity during a clinical examination. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Infrared Methods for Assessment of the Activity of Natural Enamel Caries Lesions

    PubMed Central

    Lee, Robert C.; Staninec, Michal; Le, Oanh; Fried, Daniel

    2016-01-01

    New diagnostic methods are needed for the accurate assessment of caries lesion activity to establish the need for surgical treatment. Detection of the highly mineralized surface layer that forms near the surface of the lesions as a result of remineralization is important for diagnosis of the lesion activity. Previous studies have demonstrated that novel imaging methods can be used to detect remineralization of artificial enamel caries lesions. In this paper, the activity of natural enamel caries lesions was assessed in-vitro via detection of the surface layer with PS-OCT and dehydration rate measurements with NIR reflectance and thermal imaging modalities. An automated approach for detecting the surface layer with PS-OCT yielded high sensitivity (= 0.79) and high specificity (= 0.93) with moderate correlation (R2 = 0.5920) with histology. Significant differences in dehydration rate measurements were found between the active and the arrested lesions using both the NIR reflectance and thermal imaging modalities. These results demonstrate that these novel imaging methods are ideally suited for nondestructive, noninvasive and quantitative measurement of lesion activity during a single clinical examination in real-time. PMID:27642246

  5. Pilot clinical study to assess caries lesion activity using quantitative light-induced fluorescence during dehydration

    NASA Astrophysics Data System (ADS)

    Ando, Masatoshi; Ferreira-Zandoná, Andrea G.; Eckert, George J.; Zero, Domenick T.; Stookey, George K.

    2017-03-01

    This study aimed to evaluate the ability of quantitative light-induced fluorescence (QLF) to assess caries lesion activity using visual examination (VE) as the gold standard. Twenty-four visible white spot lesions on buccal surfaces were examined from 23 children, ages 9 to 14 years. At baseline, the surface was hydrated with water, and thereafter, it was dehydrated with continuous compressed air during image acquisition. QLF images were acquired at 0 (baseline), 5, and 15 s. QLF variables [QLFV: fluorescence loss (ΔF), lesion size (S), ΔQ: ΔF×S] was recorded. Changes-in-QLFV per second (ΔQLFV) were determined: ΔQLFV=(QLFVN-QLF/N), where N indicates dehydration time. One experienced dentist conducted VE independently using a dental unit's light, compressed air, and explorer. QLFV and ΔQLFV of the active group (n=11) were compared with those of the inactive group (n=13) using two-sample t-tests. As the surface was dehydrated, S and ΔQ values of the active group increased, whereas QLFV of the inactive group showed only a small change. ΔQLFV of the active group were larger than those of the inactive group; however, the difference did not reach statistical significance (p>0.11). Within the limitations of this study, QLF data indicated increments for lesions designated as active and minimal change for lesions defined as inactive.

  6. Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma.

    PubMed

    Li, S C; Liebling, M S; Haines, K A; Weiss, J E; Prann, A

    2011-05-01

    To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U-DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions. We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U-DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences. We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U-DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS. The U-DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool. Copyright © 2011 by the American College of Rheumatology.

  7. Biomagnetic activity in ovarian lesions.

    PubMed

    Anastasiadis, P; Anninos, P; Kotini, A; Limberis, B; Galazios, G

    1998-01-01

    BACKGROUND-MATERIALS: This study aimed to investigate biomagnetic activity in benign and malignant ovarian diseases using the biomagnetometer SQUID. Magnetic recordings were obtained from 40 patients with palpable ovarian lesions. 19 of these were invasive carcinomas, and 21 were benign ovarian lesions. We used a one channel biomagnetometer SQUID (superconducting quantum interference device), in order to measure the magnetic field from benign and malignant ovarian diseases. Interestingly, the ovarian lesion waveforms and the corresponding spectral densities were of high amplitude in most (96%) malignant ovarian lesions, and of low amplitude in most (95%) benign ovarian diseases. These findings were of statistical significance (students t-test p < 0.005). It is suggested that biomagnetic measurement of benign and malignant ovarian diseases, which is an entirely new application of SQUID technology, is a promising procedure for assessing ovarian tumors.

  8. Reproducibility and diagnostic outcomes of two visual-tactile criteria used by dentists to assess caries lesion activity: a cross-over study.

    PubMed

    Tikhonova, S M; Feine, J S; Pustavoitava, N N; Allison, P J

    2014-01-01

    The aim of this study was to evaluate the reproducibility and differences in diagnostic outcomes by practicing dental clinicians previously inexperienced in using the Nyvad criteria and the ICDAS II criteria with the Lesion Activity Assessment system (ICDAS II + LAA). Four volunteer dentists were randomly allocated to one of two groups. Both groups of dentists examined the same voluntary sample (n = 140) of caries active young adults using Nyvad and ICDAS II + LAA criteria in different sequences. The first group used the Nyvad criteria during period 1, followed by ICDAS II + LAA during period 2; the second group did the examinations in the opposite sequence. Before the period 1 and 2 examinations, dentists from both groups were trained with the Nyvad or ICDAS II + LAA criteria, depending on the group to which they were assigned. Intra-examiner agreement for lesion severity was high for both diagnostic instruments (weighted kappa 0.62-0.80). For lesion activity the intra-examiner unweighted kappa values ranged from 0.31 to 0.61 for ICDAS II + LAA and from 0.36 to 0.51 for Nyvad. The mean number of active non-cavitated caries lesions was significantly higher for ICDAS II + LAA (6.14 ± 5.4) than for Nyvad (3.90 ± 3.9) (p < 0.001). Active cavitated/dentinal caries lesions were significantly higher for ICDAS II + LAA (4.14 ± 4.1) than for Nyvad (2.13 ± 3.1) (p < 0.001). Both the Nyvad and ICDAS II + LAA diagnostic criteria showed high reproducibility for lesion severity assessment. The mean number of active caries lesions among high caries risk subjects was significantly higher using the ICDAS II + LAA criteria, which may subsequently lead to more caries treatment. ISRCTN65592532.

  9. Infiltration of natural caries lesions in relation to their activity status and acid pretreatment in vitro.

    PubMed

    Neuhaus, K W; Schlafer, S; Lussi, A; Nyvad, B

    2013-01-01

    This study aimed at testing how active and inactive enamel caries lesions differ by their degree of resin infiltration, and whether the choice of acid pretreatment plays a crucial role. Four examiners assessed 104 human molars and premolars with noncavitated enamel lesions and classified them as 'active' or 'inactive' using the Nyvad criteria. Forty-five teeth were included in this study after independent unanimous lesion activity assessment. Lesions were cut perpendicularly into 2 halves. Each half lesion was pretreated with either 15% hydrochloric acid or 35% phosphoric acid. The lesions were infiltrated after staining with rhodamine isothiocyanate. Thin sections of 100 µm were prepared and the specimens were bleached with 30% hydrogen peroxide. The specimens were then counterstained with sodium fluorescein, subjected to confocal laser scanning microscopy and analyzed quantitatively. Outcome parameters were maximum and average infiltration depths as well as relative penetration depths and areas. In active lesions no significant difference of percentage maximum penetration depth and percentage average penetration depth between lesions pretreated with hydrochloric or phosphoric acid could be observed. In inactive lesions, however, phosphoric acid pretreatment resulted in significantly lower penetration compared to hydrochloric acid pretreatment. Surface conditioning with hydrochloric acid led to similar infiltration results in active and inactive lesions. Moreover, inactive lesions showed greater variability in all assessed infiltration parameters than did active lesions. In conclusion, caries lesion activity and acid pretreatment both influenced the infiltration. The use of phosphoric acid to increase permeability of the surface layer of active lesions should be further explored.

  10. Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: implications for targeted biopsies and active surveillance protocols.

    PubMed

    Boehm, Katharina; Salomon, Georg; Beyer, Burkhard; Schiffmann, Jonas; Simonis, Kathrin; Graefen, Markus; Budaeus, Lars

    2015-03-01

    Shear wave elastography allows the detection of cancer by using focused ultrasound pulses for locally deforming tissue. The differences in tissue elasticity and stiffness have been used increasingly in breast cancer imaging and help detect potential tumor lesions in the prostate. In this study we localized prostate cancer lesions using shear wave elastography before radical prostatectomy and assessed the examiner independent elasticity threshold for cancer foci detection. Shear wave elastography scanning of the whole prostate was performed before radical prostatectomy in 60 consecutive patients with high, intermediate and low risk disease. Localization of suspected lesions and density threshold (kPa) were recorded in up to 12 areas and resulted in 703 different fields. Shear wave elastography findings were correlated with final pathology. Initially 381 areas were used to establish shear wave elastography cutoffs (development cohort 32 patients). Subsequently these cutoffs were validated in 322 areas (validation cohort 28 patients). Using shear wave elastography significant differences were recorded for the elasticity of benign tissue vs prostate cancer nodules at 42 kPa (range 29 to 71.3) vs 88 kPa (range 54 to 132) (all p <0.001). Median cancer lesion diameter was 26 mm (range 18 to 41). Applying the most informative cutoff of 50 kPa to the validation cohort resulted in 80.9% and 69.1% sensitivity and specificity, respectively, and 74.2% accuracy for detecting cancer nodules based on final pathological finding. The corresponding positive and negative predictive values were 67.1% and 82.2%, respectively. Shear wave elastography allows the identification of cancer foci based on shear wave elastography differences. Moreover, reliable cutoffs for this approach can be established, allowing examiner independent localization of prostate cancer foci. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  11. Visual estimation versus different quantitative coronary angiography methods to assess lesion severity in bifurcation lesions.

    PubMed

    Grundeken, Maik J; Collet, Carlos; Ishibashi, Yuki; Généreux, Philippe; Muramatsu, Takashi; LaSalle, Laura; Kaplan, Aaron V; Wykrzykowska, Joanna J; Morel, Marie-Angèle; Tijssen, Jan G; de Winter, Robbert J; Onuma, Yoshinobu; Leon, Martin B; Serruys, Patrick W

    2017-08-24

    To compare visual estimation with different quantitative coronary angiography (QCA) methods (single-vessel versus bifurcation software) to assess coronary bifurcation lesions. QCA has been developed to overcome the limitations of visual estimation. Conventional QCA however, developed in "straight vessels," has proved to be inaccurate in bifurcation lesions. Therefore, bifurcation QCA was developed. However, the impact of these different modalities on bifurcation lesion severity classification is yet unknown METHODS: From a randomized controlled trial investigating a novel bifurcation stent (Clinicaltrials.gov NCT01258972), patients with baseline assessment of lesion severity by means of visual estimation, single-vessel QCA, 2D bifurcation QCA and 3D bifurcation QCA were included. We included 113 bifurcations lesions in which all 5 modalities were assessed. The primary end-point was to evaluate how the different modalities affected the classification of bifurcation lesion severity and extent of disease. On visual estimation, 100% of lesions had side-branch diameter stenosis (%DS) >50%, whereas in 83% with single-vessel QCA, 27% with 2D bifurcation QCA and 26% with 3D bifurcation QCA a side-branch %DS >50% was found (P < 0.0001). With regard to the percentage of "true" bifurcation lesions, there was a significant difference between visual estimate (100%), single-vessel QCA (75%) and bifurcation QCA (17% with 2D bifurcation software and 13% with 3D bifurcation software, P < 0.0001). Our study showed that bifurcation lesion complexity was significantly affected when more advanced bifurcation QCA software were used. "True" bifurcation lesion rate was 100% on visual estimation, but as low as 13% when analyzed with dedicated bifurcation QCA software. © 2017 Wiley Periodicals, Inc.

  12. Is the morphology and activity of the occlusal carious lesion related to the lesion progression stage?

    PubMed

    Neves, Aline Almeida; Vargas, Daniel Otero Amaral; Santos, Thais Maria Pires; Lopes, Ricardo Tadeu; Sousa, Frederico Barbosa

    2016-12-01

    To investigate the relationship between degree of dentin demineralization with both lesion activity and morphology of the occlusal carious cavity. Occlusal sites (n=138) were identified by visual examination (Nyvad's scores 0-6) in 67 extracted teeth which were scanned in a high energy micro-CT. After 3D reconstruction, each stack was resliced in the mesio-distal direction and tooth mineral density (MD) was measured along a path from enamel to the deepest part of dentin in the slice showing the most severe carious involvement. Each site was classified in "open" or "closed" (if cavitated) depending on the morphology of the surrounding enamel walls as measured using micro-CT and as active or inactive in enamel or dentin by a clinical scoring system. Lesions showing dentin cavitation presented higher demineralization degree compared to non-cavitated, or enamel cavitated lesions. Inactive lesions presented lower demineralization degree compared to active lesions, although with a low effect size. According to the morphological aspect of the carious cavity, open enamel lesions showed lower dentin demineralization degree than closed lesion environments. Active lesions showed higher dentin demineralization degree than inactive ones, while lesions showing closed cavitation resulted in higher dentin demineralization degree only for enamel lesions. Including those parameters in treatment decisions may help to improve prognosis and increase effectiveness of the caries diagnostic systems in the clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Assessing burn depth in tattooed burn lesions with LASCA Imaging.

    PubMed

    Krezdorn, N; Limbourg, A; Paprottka, F J; Könneker; Ipaktchi, R; Vogt, P M

    2016-09-30

    Tattoos are on the rise, and so are patients with tattooed burn lesions. A proper assessment with regard to burn depth is often impeded by the tattoo dye. Laser speckle contrast analysis (LASCA) is a technique that evaluates burn lesions via relative perfusion analysis. We assessed the effect of tattoo skin pigmentation on LASCA perfusion imaging in a multicolour tattooed patient. Depth of burn lesions in multi-coloured tattooed and untattooed skin was assessed using LASCA. Relative perfusion was measured in perfusion units (PU) and compared to various pigment colours, then correlated with the clinical evaluation of the lesion. Superficial partial thickness burn (SPTB) lesions showed significantly elevated perfusion units (PU) compared to normal skin; deep partial thickness burns showed decreased PU levels. PU of various tattoo pigments to normal skin showed either significantly lower values (blue, red, pink) or significantly increased values (black) whereas orange and yellow pigment showed values comparable to normal skin. In SPTB, black and blue pigment showed reduced perfusion; yellow pigment was similar to normal SPTB burn. Deep partial thickness burn (DPTB) lesions in tattoos did not show significant differences to normal DPTB lesions for black, green and red. Tattoo pigments alter the results of perfusion patterns assessed with LASCA both in normal and burned skin. Yellow pigments do not seem to interfere with LASCA assessment. However proper determination of burn depth both in SPTB and DPTB by LASCA is limited by the heterogenic alterations of the various pigment colours.

  14. Assessing burn depth in tattooed burn lesions with LASCA Imaging

    PubMed Central

    Krezdorn, N.; Limbourg, A.; Paprottka, F.J.; Könneker; Ipaktchi, R.; Vogt, P.M

    2016-01-01

    Summary Tattoos are on the rise, and so are patients with tattooed burn lesions. A proper assessment with regard to burn depth is often impeded by the tattoo dye. Laser speckle contrast analysis (LASCA) is a technique that evaluates burn lesions via relative perfusion analysis. We assessed the effect of tattoo skin pigmentation on LASCA perfusion imaging in a multicolour tattooed patient. Depth of burn lesions in multi-coloured tattooed and untattooed skin was assessed using LASCA. Relative perfusion was measured in perfusion units (PU) and compared to various pigment colours, then correlated with the clinical evaluation of the lesion. Superficial partial thickness burn (SPTB) lesions showed significantly elevated perfusion units (PU) compared to normal skin; deep partial thickness burns showed decreased PU levels. PU of various tattoo pigments to normal skin showed either significantly lower values (blue, red, pink) or significantly increased values (black) whereas orange and yellow pigment showed values comparable to normal skin. In SPTB, black and blue pigment showed reduced perfusion; yellow pigment was similar to normal SPTB burn. Deep partial thickness burn (DPTB) lesions in tattoos did not show significant differences to normal DPTB lesions for black, green and red. Tattoo pigments alter the results of perfusion patterns assessed with LASCA both in normal and burned skin. Yellow pigments do not seem to interfere with LASCA assessment. However proper determination of burn depth both in SPTB and DPTB by LASCA is limited by the heterogenic alterations of the various pigment colours. PMID:28149254

  15. INTERPRETING SPONTANEOUS RENAL LESIONS IN SAFETY AND RISK ASSESSMENT

    EPA Science Inventory

    Interpreting Spontaneous Renal Lesions in Safety and Risk Assessment
    Douglas C. Wolf, D.V.M., Ph.D.

    Introduction

    Risk assessment is a process whereby the potential adverse health effects from exposure to a xenobiotic are predicted after evaluation of the availab...

  16. Assessment of spatial information for hyperspectral imaging of lesion

    NASA Astrophysics Data System (ADS)

    Yang, Xue; Li, Gang; Lin, Ling

    2016-10-01

    Multiple diseases such as breast tumor poses a great threat to women's health and life, while the traditional detection method is complex, costly and unsuitable for frequently self-examination, therefore, an inexpensive, convenient and efficient method for tumor self-inspection is needed urgently, and lesion localization is an important step. This paper proposes an self-examination method for positioning of a lesion. The method adopts transillumination to acquire the hyperspectral images and to assess the spatial information of lesion. Firstly, multi-wavelength sources are modulated with frequency division, which is advantageous to separate images of different wavelength, meanwhile, the source serves as fill light to each other to improve the sensitivity in the low-lightlevel imaging. Secondly, the signal-to-noise ratio of transmitted images after demodulation are improved by frame accumulation technology. Next, gray distributions of transmitted images are analyzed. The gray-level differences is constituted by the actual transmitted images and fitting transmitted images of tissue without lesion, which is to rule out individual differences. Due to scattering effect, there will be transition zones between tissue and lesion, and the zone changes with wavelength change, which will help to identify the structure details of lesion. Finally, image segmentation is adopted to extract the lesion and the transition zones, and the spatial features of lesion are confirmed according to the transition zones and the differences of transmitted light intensity distributions. Experiment using flat-shaped tissue as an example shows that the proposed method can extract the space information of lesion.

  17. [Assessment of the relationship between trauma and meniscal lesions].

    PubMed

    Weber, M

    1994-04-01

    Until the 1930s all meniscal lesions were considered to be of traumatic origin. The efforts of Magnus and his pupils led to a more differentiated medicolegal interpretation of wear and tear of the meniscus and classification of at least some types of meniscal lesions as nontraumatic in the sense of accident insurance. This caused controversy, continuing to the present day, as to whether trauma or degeneration is essential for a meniscal tear. This debate can now be closed. Numerous investigations of meniscus pathology have proved that the isolated, essentially traumatic meniscal tear does not exist. Only if the viscoelastic properties of meniscus tissue are changed may indirect force cause a rupture. There is no longer any reason to follow principles for the assessment of meniscus damage differing from those for tendon or intervertebral disc lesions. Only penetrating joint injuries or joint fractures may lead to a direct meniscal lesion (corresponding to penetrating spine trauma or vertebral body fracture with concomitant disc lesion). Separation of the meniscus from its insertion is the analog of discoligamentous spinal trauma. Post-traumatic meniscus degeneration due to joint instability is equivalent to the instability of the motion segment with intervertebral disc degeneration. Isolated meniscal tears and isolated intervertebral disc ruptures cannot be caused by indirect force. The conventional, inconsistently applied criteria to distinguish traumatic and degenerative meniscal lesions are no longer necessary.

  18. Initial assessment of image quality for low-dose PET: evaluation of lesion detectability

    NASA Astrophysics Data System (ADS)

    Schaefferkoetter, Joshua D.; Yan, Jianhua; Townsend, David W.; Conti, Maurizio

    2015-07-01

    In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from  >40 M to  <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to-background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population.

  19. Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin.

    PubMed

    Abdel-Naser, Mohamed Badawy; Liakou, Aikaterini I; Elewa, Rana; Hippe, Sabine; Knolle, Jürgen; Zouboulis, Christos C

    2016-01-01

    Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation. © 2016 S. Karger AG, Basel.

  20. Value of modern sonography in the assessment of meniscal lesions.

    PubMed

    Wareluk, Pawel; Szopinski, Kazimierz T

    2012-09-01

    The aim of this prospective study was to assess the accuracy of modern ultrasonography in diagnostic imaging of meniscal tears. One hundred and sixty menisci were evaluated in 80 patients (42 females, 38 males, mean age=36.2 years, range=16-70 years). Inclusion criteria for the study were twofold: clinical suspicion of meniscal injury and clinical indication for arthroscopy. Knee examination was performed with the Voluson 730 Expert ultrasound system (General Electric). After sonographic examination, all patients underwent arthroscopic procedures within 1-4 days. The final diagnosis of meniscal tears was taken from surgical reports. The overall sensitivity, specificity, positive predictive value and negative predictive value of sonographic examination in the assessment of meniscal tears amounted to 85.4%, 85.7%, 67.3% and 94.4%, respectively. The statistical parameters were not statistically different in medial and lateral menisci. Age, sex, body mass index (BMI), weight, physical activity, mechanism on injury, and time lapse from injury did not have a statistically significant impact on the usefulness of ultrasonography. The highest sensitivity (>90%) was obtained in medial menisci and in patients with a BMI>25. The highest specificity (>90%) was obtained in lateral menisci, in patients after twisting injuries, in sports injuries, and in recent injuries (time lapse from the injury <1 month). The positive predictive value (PPV) of sonographic examination was higher than 90% only in recent injuries (<1 month), however, the negative predictive value of ultrasound is high, being less than 90% in males with lesions of lateral menisci and in sequelae of sports injuries.

  1. Use of overpressure to assess the role of bubbles in focused ultrasound lesion shape in vitro.

    PubMed

    Bailey, M R; Couret, L N; Sapozhnikov, O A; Khokhlova, V A; ter Haar, G; Vaezy, S; Shi, X; Martin, R; Crum, L A

    2001-05-01

    Overpressure--elevated hydrostatic pressure--was used to assess the role of gas or vapor bubbles in distorting the shape and position of a high-intensity focused ultrasound (HIFU) lesion in tissue. The shift from a cigar-shaped lesion to a tadpole-shaped lesion can mean that the wrong area is treated. Overpressure minimizes bubbles and bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature. Therefore, comparison with and without overpressure is a tool to assess the role of bubbles. Dissolution rates, bubble dynamics and boiling temperatures were determined as functions of pressure. Experiments were made first in a low-overpressure chamber (0.7 MPa maximum) that permitted imaging by B-mode ultrasound (US). Pieces of excised beef liver (8 cm thick) were treated in the chamber with 3.5 MHz for 1 to 7 s (50% duty cycle). In situ intensities (I(SP)) were 600 to 3000 W/cm(2). B-mode US imaging detected a hyperechoic region at the HIFU treatment site. The dissipation of this hyperechoic region following HIFU cessation corresponded well with calculated bubble dissolution rates; thus, suggesting that bubbles were present. Lesion shape was then tested in a high-pressure chamber. Intensities were 1300 and 1750 W/cm(2) ( +/- 20%) at 1 MHz for 30 s. Hydrostatic pressures were 0.1 or 5.6 MPa. At 1300 W/cm(2), lesions were cigar-shaped, and no difference was observed between lesions formed with or without overpressure. At 1750 W/cm(2), lesions formed with no overpressure were tadpole-shaped, but lesions formed with high overpressure (5.6 MPa) remained cigar-shaped. Data support the hypothesis that bubbles contribute to the lesion distortion.

  2. Oxidative stress enzyme and histopathological lesions in Colossoma macropomum (pisces, ariidae) for environmental impact assessment

    NASA Astrophysics Data System (ADS)

    Andrade, Ticianne de Sousa de Oliveira Mota; Sousa, Debora Batista Pinheiro; Dantas, Janaina Gomes; Castro, Jonatas da Silva; Neta, Raimunda Nonata Fortes Carvalho

    2015-12-01

    This study used oxidative stress enzyme (Glutathione S-Transferase and Catalase), histopathological lesions (Branchial lesions) and biometric data in the freshwater fish tambaqui, Colossoma macropomum, to assess environmental impacts in an Environmental Protection Area at São Luis, Brazil. Fish were sampled from two locations (A1 = contaminated area and A2 = reference site) within the protected area on four occasions. The activity of catalase (CAT) and glutathione S-transferase (GST) in C. macropomum was compared with biometric data and histopathological lesions. Results have shown that biometric data decreased significantly in fish (p<0.05) at the contaminated site. The activity of CAT was higher in fish specifically caught in A1. A significant difference was observed in the GST activity in the liver of C. macropomum when comparing fish from the contaminated site and those from the reference site (p<0.05).

  3. Assessment of remineralized dentin lesions with thermal and near-infrared reflectance imaging

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2016-02-01

    Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, ΔQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, ΔI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions.

  4. Assessment of remineralized dentin lesions with thermal and near-infrared reflectance imaging

    PubMed Central

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2016-01-01

    Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, ΔQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, ΔI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions. PMID:27006522

  5. IL-17/Th17 Pathway Is Activated in Acne Lesions

    PubMed Central

    Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

    2014-01-01

    The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

  6. Pathologic Heterogeneity Persists in Early Active Multiple Sclerosis Lesions

    PubMed Central

    Metz, Imke; Weigand, Stephen D; Popescu, Bogdan F G; Frischer, Josa M; Parisi, Joseph E; Guo, Yong; Lassmann, Hans; Brück, Wolfgang; Lucchinetti, Claudia F.

    2014-01-01

    Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed CNS inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy, were analyzed immunohistochemically. Inclusion criteria was the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at two or more time points. Results Among 1321 surgical biopsies consistent with MS, 22 cases met study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches. PMID:24771535

  7. Texture Analysis of T2-Weighted MR Images to Assess Acute Inflammation in Brain MS Lesions

    PubMed Central

    Michoux, Nicolas; Guillet, Alain; Rommel, Denis; Mazzamuto, Giosué; Sindic, Christian; Duprez, Thierry

    2015-01-01

    Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images. PMID:26693908

  8. Differential diagnosis of breast lesions by use of biomagnetic activity and non-linear analysis.

    PubMed

    Anninos, P A; Kotini, A; Koutlaki, N; Adamopoulos, A; Galazios, G; Anastasiadis, P

    2000-01-01

    Breast cancer mortality rates have not changed during the past 60 years despite significant advances in screening methods. It is tempting therefore to use novel technology in order to better understand breast oncology. In this study we investigated the biomagnetic activity obtained in benign and malignant breast lesions using a single channel biomagnetometer SQUID (Superconducting Quantum Interference Device) in order to assess the method's efficacy in the differential diagnosis of these two types of lesions and its establishment as a screening technique. Magnetic recordings were obtained from 21 patients with palpable breast lumps. Of these 11 were invasive carcinomas and 10 were benign breast lesions. We used non-linear analysis to investigate whether there is any biological differentiation in the dynamics in these two types of lesions. High amplitudes characterized the waveform of a malignant breast lesion whereas in benign breast lesions the corresponding amplitudes were low. Using the application of non-linear analysis we observed a clear saturation value for the dimension of malignant breast lesions and no saturation for benign ones. Biomagnetic measurements with the SQUID and the application of non-linear analysis are promising procedures in assessing and differentiating breast tumors.

  9. Quantitative assessment of lesion detection accuracy, resolution, and reconstruction algorithms in neutron stimulated emission computed tomography.

    PubMed

    Lakshmanan, Manu N; Kapadia, Anuj J

    2012-07-01

    We present a quantitative analysis of the image quality obtained using filtered back-projection (FBP) with Ram-Lak filtering and maximum likelihood-expectation maximization (ML-EM)-with no post-reconstruction filtering in either case-in neutron stimulated emission computed tomography (NSECT) imaging using Monte Carlo simulations in the context of clinically relevant models of liver iron overload. The ratios of pixel intensities for several regions of interest and lesion shape detection using an active-contours segmentation algorithm are assessed for accuracy across different scanning configurations and reconstruction algorithms. The modulation transfer functions (MTFs) are also computed for the cases under study and are applied to determine a minimum detectable lesion spacing as a form of sensitivity analysis. The accuracy of NSECT imaging in measuring relative tissue concentration is presented for simulated clinical liver cases. When using the 15th iteration, ML-EM provides at least 25% better resolution than FBP and proves to be highly robust under low-signal high-noise conditions prevalent in NSECT. However, FBP gives more accurate lesion pixel intensity ratios and size estimates in some cases; due to advantages provided by both reconstruction algorithms, it is worth exploring the development of an algorithm that is a hybrid of the two. We also show that NSECT imaging can be used to accurately detect 3-cm lesions in backgrounds that are a significant fraction (one-quarter) of the concentration of the lesion, down to a 4-cm spacing between lesions.

  10. Metatranscriptomics reveals overall active bacterial composition in caries lesions

    PubMed Central

    Simón-Soro, Aurea; Guillen-Navarro, Miriam; Mira, Alex

    2014-01-01

    Background Identifying the microbial species in caries lesions is instrumental to determine the etiology of dental caries. However, a significant proportion of bacteria in carious lesions have not been cultured, and the use of molecular methods has been limited to DNA-based approaches, which detect both active and inactive or dead microorganisms. Objective To identify the RNA-based, metabolically active bacterial composition of caries lesions at different stages of disease progression in order to provide a list of potential etiological agents of tooth decay. Design Non-cavitated enamel caries lesions (n=15) and dentin caries lesions samples (n=12) were collected from 13 individuals. RNA was extracted and cDNA was constructed, which was used to amplify the 16S rRNA gene. The resulting 780 bp polymerase chain reaction products were pyrosequenced using Titanium-plus chemistry, and the sequences obtained were used to determine the bacterial composition. Results A mean of 4,900 sequences of the 16S rRNA gene with an average read length of 661 bp was obtained per sample, giving a comprehensive view of the active bacterial communities in caries lesions. Estimates of bacterial diversity indicate that the microbiota of cavities is highly complex, each sample containing between 70 and 400 metabolically active species. The composition of these bacterial consortia varied among individuals and between caries lesions of the same individuals. In addition, enamel and dentin lesions had a different bacterial makeup. Lactobacilli were found almost exclusively in dentin cavities. Streptococci accounted for 40% of the total active community in enamel caries, and 20% in dentin caries. However, Streptococcus mutans represented only 0.02–0.73% of the total bacterial community. Conclusions The data indicate that the etiology of dental caries is tissue dependent and that the disease has a clear polymicrobial origin. The low proportion of mutans streptococci detected confirms that they

  11. Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

    PubMed

    Nowak, Przemyslaw; Jochem, Jerzy; Zwirska-Korczala, Krystyna; Josko, Jadwiga; Noras, Lukasz; Kostrzewa, Richard M; Brus, Ryszard

    2008-04-01

    To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity several-fold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum--reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

  12. Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS.

    PubMed

    Pinto-Sarmento, Tássia Cristina de Almeida; Abreu, Mauro Henrique; Gomes, Monalisa Cesarino; Costa, Edja Maria Melo de Brito; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2016-01-01

    The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05-2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65-3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07-2.23). Lesion activity was significantly associated with mother's schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15-4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother's schooling.

  13. A quantitative assay for assessing the effects of DNA lesions on transcription.

    PubMed

    You, Changjun; Dai, Xiaoxia; Yuan, Bifeng; Wang, Jin; Wang, Jianshuang; Brooks, Philip J; Niedernhofer, Laura J; Wang, Yinsheng

    2012-10-01

    Most mammalian cells in nature are quiescent but actively transcribing mRNA for normal physiological processes; thus, it is important to investigate how endogenous and exogenous DNA damage compromises transcription in cells. Here we describe a new competitive transcription and adduct bypass (CTAB) assay to determine the effects of DNA lesions on the fidelity and efficiency of transcription. Using this strategy, we demonstrate that the oxidatively induced lesions 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine (cdG) and the methylglyoxal-induced lesion N(2)-(1-carboxyethyl)-2'-deoxyguanosine (N(2)-CEdG) strongly inhibited transcription in vitro and in mammalian cells. In addition, cdA and cdG, but not N(2)-CEdG, induced transcriptional mutagenesis in vitro and in vivo. Furthermore, when located on the template DNA strand, all examined lesions were primarily repaired by transcription-coupled nucleotide excision repair in mammalian cells. This newly developed CTAB assay should be generally applicable for quantitatively assessing how other DNA lesions affect DNA transcription in vitro and in cells.

  14. Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

    PubMed Central

    Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

    2012-01-01

    Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting

  15. Primary Cystic Lesions of the Retrorectal Space: MRI Evaluation and Clinical Assessment.

    PubMed

    Dwarkasing, Roy S; Verschuuren, Sylvia I; van Leenders, Geert J L H; Braun, Loes M M; Krestin, Gabriel P; Schouten, W Rudolph

    2017-10-01

    The purpose of this study was to assess the a priori chance that primary cystic lesions of the retrorectal space are malignant and to investigate MRI characteristics that indicate malignancy. Patients referred to a center for colorectal surgery were recruited from 2000 to 2014. Lesions were proven by clinical assessment and histopathology. MRI was performed at 1.5 T with examinations evaluated by two radiologists. Interobserver agreement was assessed (Cohen kappa) and differences between malignant and benign lesions calculated (Fisher exact test). Twenty-eight patients (22 women, six men; age range, 18-70 years) with 31 lesions were included. Lesions were categorized as tailgut cysts (n = 16, 52%), teratomas (n = 9, 29%), lesions of colorectal origin (n = 4, 13%), or neurogenic lesions (n = 2, 6%). Five patients (18%) had malignant lesions. Colorectal lesions had the highest percentage of malignancy (3/4, 75%). A solid tissue component was found in all five (100%) malignant lesions and two (8%) of the benign lesions, which were both teratomas (p < 0.05). Sensitivity and specificity for malignancy according to the presence of a solid tissue component was 100% (5/5) and 92% (24/26). For unilocularity, multilocularity, debris, septa, and wall thickening, differences were not significant. Interobserver agreement was excellent (κ = 1) for all characteristics except debris (κ = 0.795). The majority of retrorectal cystic lesions are benign. The presence of a solid tissue component should raise suspicion for malignancy.

  16. Assessment of cavitation in artificial approximal dental lesions with near-IR imaging

    NASA Astrophysics Data System (ADS)

    Simon, Jacob C.; Darling, Cynthia L.; Fried, Daniel

    2017-02-01

    Bitewing radiography is still considered state-of-the-art diagnostic technology for assessing cavitation within approximal carious dental lesions, even though radiographs cannot resolve cavitated surfaces but instead are used to measure lesion depth in order to predict cavitation. Clinicians need new technologies capable of determining whether approximal carious lesions have become cavitated because not all lesions progress to cavitation. Assessing lesion cavitation from near-infrared (NIR) imaging methods holds great potential due to the high transparency of enamel in the NIR region from λ=1300-1700-nm, which allows direct visualization and quantified measurements of enamel demineralization. The objective of this study was to measure the change in lesion appearance between non-cavitated and cavitated lesions in artificially generated lesions using NIR imaging modalities (two-dimensional) at λ=1300-nm and λ=1450-nm and cross-polarization optical coherence tomography (CP-OCT) (thee-dimensional) λ=1300-nm. Extracted human posterior teeth with sound proximal surfaces were chosen for this study and imaged before and after artificial lesions were made. A high speed dental hand piece was used to create artificial cavitated proximal lesions in sound samples and imaged. The cavitated artificial lesions were then filled with hydroxyapatite powder to simulate non-cavitated proximal lesions.

  17. Assessment of cavitation in artificial approximal dental lesions with near-IR imaging.

    PubMed

    Simon, Jacob C; Darling, Cynthia L; Fried, Daniel

    2017-01-28

    Bitewing radiography is still considered state-of-the-art diagnostic technology for assessing cavitation within approximal carious dental lesions, even though radiographs cannot resolve cavitated surfaces but instead are used to measure lesion depth in order to predict cavitation. Clinicians need new technologies capable of determining whether approximal carious lesions have become cavitated because not all lesions progress to cavitation. Assessing lesion cavitation from near-infrared (NIR) imaging methods holds great potential due to the high transparency of enamel in the NIR region from λ=1300-1700-nm, which allows direct visualization and quantified measurements of enamel demineralization. The objective of this study was to measure the change in lesion appearance between non-cavitated and cavitated lesions in artificially generated lesions using NIR imaging modalities (two-dimensional) at λ =1300-nm and λ=1450-nm and cross-polarization optical coherence tomography (CP-OCT) (thee-dimensional) λ =1300-nm. Extracted human posterior teeth with sound proximal surfaces were chosen for this study and imaged before and after artificial lesions were made. A high speed dental hand piece was used to create artificial cavitated proximal lesions in sound samples and imaged. The cavitated artificial lesions were then filled with hydroxyapatite powder to simulate non-cavitated proximal lesions.

  18. Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis.

    PubMed

    Peferoen, Laura A N; Vogel, Daphne Y S; Ummenthum, Kimberley; Breur, Marjolein; Heijnen, Priscilla D A M; Gerritsen, Wouter H; Peferoen-Baert, Regina M B; van der Valk, Paul; Dijkstra, Christine D; Amor, Sandra

    2015-01-01

    Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro.

  19. Improved assessment of renal lesions in pregnancy with magnetic resonance imaging.

    PubMed

    Putra, Lydia G Johns; Minor, Thomas X; Bolton, Damien M; Appu, Sreevinas; Dowling, Caroline R; Neerhut, Gregory J

    2009-09-01

    To ascertain the potential utility of magnetic resonance imaging in providing additional clarification of those solid renal mass lesions identified at routine antenatal ultrasonography in early pregnancy and influencing the management of such lesions. We present 7 patients in whom magnetic resonance imaging was used to diagnose, stage, and monitor renal lesions detected during pregnancy. Magnetic resonance imaging provided for improved imaging of renal mass lesions identified at antenatal ultrasonography, without the use of ionizing radiation, and permitted management determined by optimal radiographic assessment of such lesions without fetal irradiation. Magnetic resonance imaging is the most appropriate method to further investigate renal masses identified at routine antenatal ultrasonography early in pregnancy.

  20. Intraoral pH measurement of carious lesions with qPCR of cariogenic bacteria to differentiate caries activity.

    PubMed

    Kuribayashi, Megumi; Kitasako, Yuichi; Matin, Khairul; Sadr, Alireza; Shida, Kanako; Tagami, Junji

    2012-03-01

    A low pH environment is created by cariogenic bacteria. This study was aimed to measure pH of carious lesions intraorally using a micro-pH sensor, and assess predominant acid-producing cariogens by qPCR to differentiate caries activities. 103 dentine lesions classified as active or arrested caries based on the clinical and radiological examinations were collected from patients after intraoral measurement of the lesion surface pH using a micro-pH sensor. Quantitative detection of genomic DNA copies of target cariogenic bacteria (mutans streptococci and Lactobacillus spp.) in each lesion was performed using real-time PCR. Correlation between the pH ranges and the number of bacterial species was examined by Spearman test. 50 samples were diagnosed as active and 53 as arrested lesions. Statistically significant difference was observed on average surface pH value between active and arrested lesions (p<0.05). Prevalence of Lactobacillus spp. was higher in active lesions than in arrested lesions (76% vs. 58% of samples, respectively). When the carious lesions were categorised into four different pH ranges (up to 5.5, from 5.6 to 5.8, from 5.9 to 6.1 and 6.2 or above), increased prevalence of Lactobacillus spp. was observed with decrease of pH levels. A significant negative relationship was found between pH value and number of Lactobacillus spp. (r=-0.209, p<0.05) but no such correlation was found for mutans streptococci. Intraoral pH measurement might be clinically useful to determine acidity of the local environment of carious lesions as one aspect of the caries activity assessment. The population of certain bacteria may indicate activity of carious lesions. Intraoral pH measurement of the carious lesions using a micro-pH sensor may be a clinically feasible method for assessment of lesion acidity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS

    PubMed Central

    Pinto-Sarmento, Tássia Cristina de Almeida; Abreu, Mauro Henrique; Gomes, Monalisa Cesarino; Costa, Edja Maria Melo de Brito; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2016-01-01

    The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05–2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65–3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07–2.23). Lesion activity was significantly associated with mother’s schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15–4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother’s schooling. PMID:26900846

  2. Atrial lesion transmurality assessment using multi-fiber diffuse reflectance (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Singh-Moon, Rajinder P.; Hendon, Christine P.

    2017-02-01

    In non-pharmacological treatment of cardiac arrhythmias such as catheter ablation therapy, long-term treatment effectiveness is related in part to the quality of lesion generation. Superficial lesions may lead to arrhythmia recurrence by allowing recovery along conduction channels for arrhythmic impulses to propagate; conversely transmural lesions inhibit conduction. Conventional techniques rely on measurement of surrogate parameters such as change in bioelectrical impedance, or electrogram amplitude dampening as a qualitative assessment for lesion size. In previous work, we've demonstrated a relationship between lesion dimensions and spectroscopic parameters extracted using an optically-integrated ablation catheter. Though these metrics present some trend, a method to directly assess lesion transmurality maybe better suited. In this work, we report a method for direct recovery of lesion depth in cardiac tissue using diffusely reflected optical measurements and present initial in silico validation. Photon transport throughout a heterogeneous volume was simulated for a series of source-detector pairs and optical properties using a GPU-based Monte Carlo (MC) code. Results were used to generate a multi-dimensional look-up table for each collection geometry for partial to transmural lesions. A genetic algorithm-based two-step inversion method was employed to extract lesion transmurality. MC simulated optical measurements for various lesion sizes were generated using optical properties for ablated and normal cardiac tissue found in literature and were fitted using our algorithm. Recovered lesion depths ranged between 2-10% for lesions less than 3mm and were within 20% for lesions greater than 4mm. These results support the application of this technique for lesion validation for atrial tissue.

  3. Ontogenetic serotoninergic lesioning alters histaminergic activity in rats in adulthood.

    PubMed

    Jośko, Jadwiga; Drab, Jacek; Jochem, Jerzy; Nowak, Przemysław; Szkilnik, Ryszard; Korossy-Mruk, Eva; Boroń, Dariusz; Kostrzewa, Richard M; Brus, Halina; Brus, Ryszard

    2011-08-01

    The aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats lesioned as neonates with the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At 3 days after birth Wistar rats were pretreated with desipramine (20 mg/kg ip) before bilateral icv administration of 5,7-DHT (37.5 μg base on each side) or saline-ascorbic (0.1%) vehicle (control). At 10 week levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were determined in frontal cortex, striatum, and hippocampus by an HPLC/ED technique. In the hypothalamus, frontal cortex, hippocampus and medulla oblongata, the level of histamine was analyzed by an immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped activity) were performed, and effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists S(+)chlorpheniramine (H(1)), cimetidine (H(2)), and thioperamide (H(3)) were determined. We confirmed that 5,7-DHT profoundly reduced contents of 5-HT and 5-HIAA in the brain in adulthood. Histamine content was also reduced in all examined brain regions. Moreover, in 5,7-DHT-lesioned rats the locomotor and oral activity responses to thioperamide were altered, and apomorphine-induced stereotype was intensified. From the above, we conclude that an intact central serotoninergic system modulates histamine H(3) receptor antagonist effects on the dopaminergic neurons in rats.

  4. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions.

    PubMed

    Dombrowski, Yvonne; Peric, Mark; Koglin, Sarah; Kammerbauer, Claudia; Göss, Christine; Anz, David; Simanski, Maren; Gläser, Regine; Harder, Jürgen; Hornung, Veit; Gallo, Richard L; Ruzicka, Thomas; Besch, Robert; Schauber, Jürgen

    2011-05-11

    The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activates inflammasomes containing the DNA sensor AIM2. In this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions but not in healthy skin. In cultured keratinocytes, interferon-γ induced AIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that can trigger AIM2 inflammasome and IL-1β activation in psoriasis. Furthermore, cathelicidin LL-37 interfered with DNA-sensing inflammasomes, which thereby suggests an anti-inflammatory function for this peptide. Thus, our data reveal a link between the AIM2 inflammasome, cathelicidin LL-37, and autoinflammation in psoriasis, providing new potential targets for the treatment of this chronic skin disease.

  5. Are Imaging and Lesioning Convergent Methods for Assessing Functional Specialisation? Investigations Using an Artificial Neural Network

    ERIC Educational Resources Information Center

    Thomas, Michael S. C.; Purser, Harry R. M.; Tomlinson, Simon; Mareschal, Denis

    2012-01-01

    This article presents an investigation of the relationship between lesioning and neuroimaging methods of assessing functional specialisation, using synthetic brain imaging (SBI) and lesioning of a connectionist network of past-tense formation. The model comprised two processing "routes": one was a direct route between layers of input and output…

  6. Are Imaging and Lesioning Convergent Methods for Assessing Functional Specialisation? Investigations Using an Artificial Neural Network

    ERIC Educational Resources Information Center

    Thomas, Michael S. C.; Purser, Harry R. M.; Tomlinson, Simon; Mareschal, Denis

    2012-01-01

    This article presents an investigation of the relationship between lesioning and neuroimaging methods of assessing functional specialisation, using synthetic brain imaging (SBI) and lesioning of a connectionist network of past-tense formation. The model comprised two processing "routes": one was a direct route between layers of input and output…

  7. Segmentation of lung lesions on CT scans using watershed, active contours, and Markov random field

    PubMed Central

    Tan, Yongqiang; Schwartz, Lawrence H.; Zhao, Binsheng

    2013-01-01

    Purpose: Lung lesions vary considerably in size, density, and shape, and can attach to surrounding anatomic structures such as chest wall or mediastinum. Automatic segmentation of the lesions poses a challenge. This work communicates a new three-dimensional algorithm for the segmentation of a wide variety of lesions, ranging from tumors found in patients with advanced lung cancer to small nodules detected in lung cancer screening programs. Methods: The authors’ algorithm uniquely combines the image processing techniques of marker-controlled watershed, geometric active contours as well as Markov random field (MRF). The user of the algorithm manually selects a region of interest encompassing the lesion on a single slice and then the watershed method generates an initial surface of the lesion in three dimensions, which is refined by the active geometric contours. MRF improves the segmentation of ground glass opacity portions of part-solid lesions. The algorithm was tested on an anthropomorphic thorax phantom dataset and two publicly accessible clinical lung datasets. These clinical studies included a same-day repeat CT (prewalk and postwalk scans were performed within 15 min) dataset containing 32 lung lesions with one radiologist's delineated contours, and the first release of the Lung Image Database Consortium (LIDC) dataset containing 23 lung nodules with 6 radiologists’ delineated contours. The phantom dataset contained 22 phantom nodules of known volumes that were inserted in a phantom thorax. Results: For the prewalk scans of the same-day repeat CT dataset and the LIDC dataset, the mean overlap ratios of lesion volumes generated by the computer algorithm and the radiologist(s) were 69% and 65%, respectively. For the two repeat CT scans, the intra-class correlation coefficient (ICC) was 0.998, indicating high reliability of the algorithm. The mean relative difference was −3% for the phantom dataset. Conclusions: The performance of this new segmentation

  8. Lesion insertion in projection domain for computed tomography image quality assessment

    NASA Astrophysics Data System (ADS)

    Chen, Baiyu; Ma, Chi; Yu, Zhicong; Leng, Shuai; Yu, Lifeng; McCollough, Cynthia

    2015-03-01

    To perform task-based image quality assessment in CT, it is desirable to have a large number of realistic patient images with known diagnostic truth. One effective way to achieve this objective is to create hybrid images that combine patient images with simulated lesions. Because conventional hybrid images generated in the image-domain fails to reflect the impact of scan and reconstruction parameters on lesion appearance, this study explored a projection-domain approach. Liver lesion models were forward projected according to the geometry of a commercial CT scanner to acquire lesion projections. The lesion projections were then inserted into patient projections (decoded from commercial CT raw data with the assistance of the vendor) and reconstructed to acquire hybrid images. To validate the accuracy of the forward projection geometry, simulated images reconstructed from the forward projections of a digital ACR phantom were compared to physically acquired ACR phantom images. To validate the hybrid images, lesion models were inserted into patient images and visually assessed. Results showed that the simulated phantom images and the physically acquired phantom images had great similarity in terms of HU accuracy and high-contrast resolution. The lesions in the hybrid image had a realistic appearance and merged naturally into the liver background. In addition, the inserted lesion demonstrated reconstruction-parameter-dependent appearance. Compared to conventional image-domain approach, our method enables more realistic hybrid images for image quality assessment.

  9. Postreplication gaps at UV lesions are signals for checkpoint activation

    PubMed Central

    Callegari, A. John; Clark, Emily; Pneuman, Amanda; Kelly, Thomas J.

    2010-01-01

    Exposure of eukaryotic cells to UV light induces a checkpoint response that delays cell-cycle progression after cells enter S phase. It has been hypothesized that this checkpoint response provides time for repair by signaling the presence of structures generated when the replication fork encounters UV-induced DNA damage. To gain insight into the nature of the signaling structures, we used time-lapse microscopy to determine the effects of deficiencies in translesion DNA polymerases on the checkpoint response of the fission yeast Schizosaccharomyces pombe. We found that disruption of the genes encoding translesion DNA polymerases Polκ and Polη significantly prolonged the checkpoint response, indicating that the substrates of these enzymes are signals for checkpoint activation. Surprisingly, we found no evidence that the translesion polymerases Rev1 and Polζ repair structures that are recognized by the checkpoint despite their role in maintaining viability after UV irradiation. Quantitative flow cytometry revealed that cells lacking translesion polymerases replicate UV-damaged DNA at the same rate at WT cells, indicating that the enhanced checkpoint response of cells lacking Polκ and Polη is not the result of stalled replication forks. These observations support a model in which postreplication DNA gaps with unrepaired UV lesions in the template strand act both as substrates for translesion polymerases and as signals for checkpoint activation. PMID:20404181

  10. Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

    PubMed

    Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

    2013-03-01

    Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Microglial cell activation in demyelinating canine distemper lesions.

    PubMed

    Stein, Veronika M; Czub, Markus; Schreiner, Nicole; Moore, Peter F; Vandevelde, Marc; Zurbriggen, Andreas; Tipold, Andrea

    2004-08-01

    Microglia cells are the principal immune effector elements of the brain responding to any pathological event. To elucidate the possible role of microglia in initial non-inflammatory demyelination in canine distemper virus (CDV) infection, microglia from experimentally CDV infected dogs were isolated ex vivo by density gradient centrifugation and characterized immunophenotypically and functionally using flow cytometry. Results from dogs with demyelinating lesions were compared to results from recovered dogs and two healthy controls. CDV antigen could be detected in microglia of dogs with histopathologically confirmed demyelination. Microglia of these dogs showed marked upregulation of the surface molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86), whereas no increased expression was found for CD44 and CD45. Functionally, microglia exhibited distinctly enhanced phagocytosis and generation of reactive oxygen species (ROS). It was concluded that in CDV infection, there is a clear association between microglial activation and demyelination. This strongly suggests that microglia contribute to acute myelin destruction in distemper.

  12. Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice.

    PubMed

    Astudillo, Luis; Rodriguez, Jaime A; Schmeda-Hirschmann, Guillermo

    2002-04-01

    The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on gastric ulceration in rats. The effect of a single oral dose of OA was evaluated at 50, 100 and 200 mg kg(-1) in the following models: pylorus ligature (Shay), and aspirin- and ethanol-induced gastric ulcers. A single oral administration of OA at doses of 50, 100 and 200 mg kg-' inhibited the appearance of gastric lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature and aspirin models, the effect of OA at the selected concentrations was comparable with that of ranitidine at 50 mg kg(-1). In the ethanol-induced gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg kg(-1) was as active as omeprazole at 20 mg kg(-1). The effect of OA, its acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were assessed on HCI/ethanol-induced ulcers in mice at 200 mg kg(-1). OA and its methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in this animal model. The semisynthetic derivatives OAM and OAAM had the greatest gastroprotective activity, but their effect was not significantly greater than OA. In an acute toxicity test on mice, intraperitoneal administration of OA showed no toxicity at doses up to 600 mg kg(-1).

  13. A survey of survival and activity of citrus canker lesion populations on foliage, fruit and shoots in a Florida grapefruit orchard in 2009 and 2010

    USDA-ARS?s Scientific Manuscript database

    Citrus canker (Xanthomonas citri subsp. citri (Xcc)) can infect several species of citrus. The disease can develop on the leaves, shoots and fruit, causing erumpent lesions, that on fruit precludes sale to the fresh market. We assessed lesion activity in orchard-grown grapefruit to provide informa...

  14. Maternal separation and lesion of adtn alters anxiety and adrenal activity in male rats.

    PubMed

    Esquivel, Bárbara Bárcena; Levin, Gloria; Rivarola, María Angélica; Suárez, Marta Magdalena

    2009-01-01

    The present study investigated the effect of early maternal separation on anxiety and hypophyso-adrenal system activity to anterodorsal thalamic nuclei (ADTN) lesion in male rats as adults in order to compare this with previous results with female rats. During the first 3 weeks of life, male rats were isolated 4.5 hr daily and tested as adults. Thirty days after ADTN lesion we found that adrenocorticotropic hormone (ACTH) plasma levels were affected neither by maternal separation nor by ADTN lesion. Plasma corticosterone (CORT) concentration was increased with lesion of the ADTN in maternally separated rats. A significant increase in plasma catecholamine concentration was induced by early maternal separation. In ADTN-lesioned rats, plasma norepinephrine (NE) concentration was significantly lower than in the respective sham-lesioned groups. In terms of anxiety, there were no significant effects of early experience. However, the ADTN lesion tended to decrease anxiety-related behavior.

  15. Clinical Assessment of Physical Examination Maneuvers for Rotator Cuff Lesions.

    PubMed

    Somerville, Lyndsay E; Willits, Kevin; Johnson, Andrew M; Litchfield, Robert; LeBel, Marie-Eve; Moro, Jaydeep; Bryant, Dianne

    2014-08-01

    Shoulder pain and disability pose a diagnostic challenge for clinicians owing to the numerous causes that exist. Unfortunately, the evidence in support of most clinical tests is weak or absent. To determine the diagnostic validity of physical examination maneuvers for rotator cuff lesions. Cohort study (diagnosis); Level of evidence, 1. Consecutive shoulder patients recruited for this study were referred to 2 tertiary orthopaedic clinics. A surgeon took a thorough history and indicated his or her certainty about each possible diagnosis. A clinician performed the physical examination for diagnoses where uncertainty remained. Arthroscopy was considered the reference standard for patients who underwent surgery, and MRI with arthrogram was considered the reference for patients who did not. The sensitivity, specificity, and likelihood ratios were calculated to investigate whether combinations of the top tests provided stronger predictions of the presence or absence of disease. There were 139 participants. None of the tests were highly sensitive for diagnosing rotator cuff tears or tendinosis. Tests for subscapularis tears were all highly specific. No optimal combination of tests improved the ability to correctly diagnose rotator cuff tears. Closer analysis revealed the internal rotation and lateral rotation lag sign did not improve the ability to diagnose subscapularis or supraspinatus tears, respectively, although the lateral rotation lag sign demonstrated a discriminatory ability for tear size. No test in isolation is sufficient to diagnose a patient with rotator cuff damage. A combination of tests improves the ability to diagnose damage to the rotator cuff. It is recommended that the internal rotation and lateral rotation lag signs be removed from the gamut of physical examination tests for supraspinatus and subscapularis tears. © 2014 The Author(s).

  16. Active nonsurgical decompression of large periapical lesions--3 case reports.

    PubMed

    Mejia, Jose L; Donado, Jaime E; Basrani, Bettina

    2004-11-01

    This paper describes a new nonsurgical approach for treating large periapical lesions which involves using a modified vacuum system within the root canal space. This new technique produces a vacuum effect in the periapical zone, which facilitates evacuation of large amounts of inflammatory fluids. This technique was used in 3 clinical cases, in which the patients presented with copious amounts of exudate draining from within the root canals. Clinical and radiographic results showed long-term resolution of the endodontic lesions. This treatment of the periapical pathology was consistent with the principles of conservative, nonsurgical endodontic procedures.

  17. Use of articulated registration for response assessment of individual metastatic bone lesions

    NASA Astrophysics Data System (ADS)

    Yip, Stephen; Jeraj, Robert

    2014-03-01

    Accurate skeleton registration is necessary to match corresponding metastatic bone lesions for response assessment over multiple scans. In articulated registration (ART), whole-body skeletons are registered by auto-segmenting individual bones, then rigidly aligning them. Performance and robustness of the ART in lesion matching were evaluated and compared to other commonly used registration techniques. Sixteen prostate cancer patients were treated either with molecular targeted therapy or chemotherapy. Ten out of the 16 patients underwent the double baseline whole-body [F-18]NaF PET/CT scans for test-retest (TRT) evaluation. Twelve of the 16 patients underwent pre- and mid-treatment [F-18]NaF PET/CT scans. Skeletons at different time points were registered using ART, rigid, and deformable (DR) registration algorithms. The corresponding lesions were contoured and identified on successive PET images based on including the voxels with the standardized uptake value over 15. Each algorithm was evaluated for its ability to accurately align corresponding lesions via skeleton registration. A lesion matching score (MS) was measured for each lesion, which quantified the per cent overlap between the lesion's two corresponding contours. Three separate sensitivity studies were conducted to investigate the robustness of ART in matching: sensitivity of lesion matching to various contouring threshold levels, effects of imperfections in the bone auto-segmentation and sensitivity of mis-registration. The performance of ART (MS = 82% for both datasets, p ≪ 0.001) in lesion matching was significantly better than rigid (MSTRT = 53%, MSResponse = 46%) and DR (MSTRT = 46%, MSResponse = 45%) algorithms. Neither varying threshold levels for lesion contouring nor imperfect bone segmentation had significant (p∼0.10) impact on the ART matching performance as the MS remained unchanged. Despite the mis-registration reduced MS for ART, as low as 67% (p ≪ 0.001), the performance remained to

  18. [CT perfusion for assessment of brain stem ischemic lesions].

    PubMed

    Saifullina, E I; Iksanova, G R

    2007-01-01

    Modern neurovisualization modalities - CT and MRI with cerebral circulation assessment was used for diagnosis of cerebrovascular disturbances in patients admitted to the Emergency Care Hospital of Ufa. CT and MRI perfusion methods appeared to be highly effective both in diagnosis and treatment efficacy monitoring of acute stroke.

  19. Diffusion-weighted imaging in the characterization of focal liver lesions: efficacy of visual assessment.

    PubMed

    Battal, Bilal; Kocaoglu, Murat; Akgun, Veysel; Karademir, Ibrahim; Deveci, Salih; Guvenc, Inanc; Bulakbasi, Nail

    2011-01-01

    The objective of the study was to assess the value of visual assessment of signal intensities on b800 diffusion-weighted images and apparent diffusion coefficient (ADC) maps in differentiation of benign and malignant focal liver lesions (FLLs). Approval for this retrospective study was obtained from the institutional review board. One hundred forty-three FLLs in 65 patients (38 women, 27 men; mean age, 50.8 years) underwent magnetic resonance (MR) imaging and diffusion-weighted imaging (DWI) with a respiratory-triggered single-shot echo-planar imaging sequence. Focal liver lesions were evaluated visually according to the signal intensities on b800 and ADC map images, and ADC values were also calculated. The conventional MR imaging, follow-up imaging findings, and histopathologic data were regarded as gold standard. Normal distribution was assessed with Kolmogorov-Smirnov test. The accuracies of visual assessment and ADC values in differentiating benign and malignant FLLs were assessed with the Student t test, and threshold values were determined with receiver operating characteristic curve analysis. By using a cutoff value of 1.21 × 10⁻³ mm²/s, ADC had a sensitivity of 100%, a specificity of 89.3%, and an accuracy of 92.3% in the discrimination of malignant FLLs. With the visual assessment of the DWIs and ADC maps, malignant lesions were differentiated from benign ones, with 100% sensitivity, 92.2% specificity, and 94.4% accuracy. Although some benign lesions were interpreted as malignant, no malignant lesion was determined as benign in visual assessment. Most FLLs are benign ones such as hemangiomas and cysts, which can be readily and practically characterized only by using visual assessment of DWIs without requiring time-consuming conventional and dynamic contrast-enhanced imaging sequences. Some benign lesions that are falsely interpreted as malignant can be further characterized by using conventional and contrast-enhanced MR studies.

  20. Mesenchymal stem cells as active prohealing and immunosuppressive agents in periapical environment: evidence from human and experimental periapical lesions.

    PubMed

    Araujo-Pires, Ana Claudia; Biguetti, Claudia Cristina; Repeke, Carlos Eduardo; Rodini, Camila de Oliveira; Campanelli, Ana Paula; Trombone, Ana Paula Favaro; Letra, Ariadne; Silva, Renato Menezes; Garlet, Gustavo Pompermaier

    2014-10-01

    Previous studies describe contrasting molecular profiles of active and inactive periapical granulomas characterized by distinct expression of cytokines, osteoclastogenic factors, and wound healing markers. Although the molecular mechanisms underlying such a dichotomy remain unknown, in this study we investigated the potential involvement of mesenchymal stem cells (MSCs) in determining human and murine periapical lesion activity and outcomes. Periapical granulomas (n = 83) and control samples (n = 24) were comparatively assessed for the expression levels of 11 mesenchymal stem cell (MSC) markers using real-time polymerase chain reaction. Experimental periapical lesions induced in mice were evaluated for MSC marker expression and the effects of AMD3100 treatment on lesion outcomes. MCS marker expression was prevalent in periapical granulomas compared with that in controls, whereas CD29, CD73, CD90, CD146, CD166, NANOG, Stro-1, and CXCR4 expressions were higher in inactive than in active lesions. Experimental periapical lesion inactivity was also associated with an increased expression of MSC markers. The inhibition of MSC mobilization to the periapex by AMD3100 resulted in increased lesion sizes; decreased expression of MSCs and wound healing markers; and increased expression of interleukin 1 beta (IL-17β), interleukin 17 (IL-17), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and nuclear factor kappa-B ligand (RANKL). Our results show that MSC markers are overexpressed in inactive human and experimental periapical lesions and that MSC mobilization results in the attenuation of experimental lesion progression associated with immunosuppressive and prohealing mechanisms. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  1. Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations

    PubMed Central

    Nojima, Masanori; Harada, Taku; Maruyama, Reo; Ashida, Masami; Aoki, Hironori; Matsushita, Hiro-o; Yoshikawa, Kenjiro; Harada, Eiji; Tanaka, Yoshihito; Wakita, Shigenori; Niinuma, Takeshi; Kai, Masahiro; Eizuka, Makoto; Sugai, Tamotsu; Suzuki, Hiromu

    2016-01-01

    To clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions' clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect. PMID:27145369

  2. Assessment of texture analysis on DCE-MRI data for the differentiation of breast tumor lesions

    NASA Astrophysics Data System (ADS)

    Loose, Jennifer; Harz, Markus T.; Laue, Hendrik; Twellmann, Thorsten; Bick, Ulrich; Rominger, Marga; Hahn, Horst K.; Peitgen, Heinz-Otto

    2009-02-01

    Breast cancer diagnosis based on magnetic resonance images (breast MRI) is increasingly being accepted as an additional diagnostic tool to mammography and ultrasound, with distinct clinical indications.1 Its capability to detect and differentiate lesion types with high sensitivity and specificity is countered by the fact that visual human assessment of breast MRI requires long experience. Moreover, the lack of evaluation standards causes diagnostic results to vary even among experts. The most important MR acquisition technique is dynamic contrast enhanced (DCE) MR imaging since different lesion types accumulate contrast material (CM) differently. The wash-in and wash-out characteristic as well as the morphologic characteristic recorded and assessed from MR images therefore allows to differentiate benign from malignant lesions. In this work, we propose to calculate second order statistical features (Haralick textures) for given lesions based on subtraction and 4D images and on parametermaps. The lesions are classified with a linear classification scheme into probably malignant or probably benign. The method and model was developed on 104 histologically graded lesions (69 malignant and 35 benign). The area under the ROC curve obtained is 0.91 and is already comparable to the performance of a trained radiologist.

  3. Assessing the arsenic-contaminated rice (Oryza sativa) associated children skin lesions.

    PubMed

    Liao, Chung-Min; Lin, Tzu-Ling; Hsieh, Nan-Hung; Chen, Wei-Yu

    2010-04-15

    The purpose of this study was to assess the potential risk of children skin lesions from arsenic-contaminated rice (Oryza sativa) consumption in West Bengal (India). Published age- and gender-specific skin lesions data in West Bengal were reanalyzed and incorporated into a Weibull dose-response model to predict children skin lesion prevalence. Monomethylarsonous acid (MMA(III)) levels in urine was used as a biomarker that could be predicted from a human physiologically based pharmacokinetic (PBPK) model. This study integrated arsenic contents in irrigation water, bioaccumulation factors of paddy soil, cooking methods, and arsenic bioavailability of cooked rice in gastrointestinal tract into a probabilistic risk model. Results indicated that children aged between 13 and 18 years might pose a relative higher potential risk of skin lesions to arsenic-contaminated cooked rice (odds ratios (ORs)=1.18 (95% CI 1.12-2.15)) than those of 1-6 years children (ORs=0.98 (0.85-1.40)). This study revealed the need to consider the relationships between cooking method and arsenic in cooked rice when assessing the risk associated with children skin lesions from rice consumption. This study suggested that arsenic-associated skin lesions risk from arsenic-contaminated rice consumption would be reduced significantly by adopting traditional rice cooking method (wash until clean; rice:water=1:6; discard excess water) as followed in West Bengal (India) and using water containing lower arsenic (e.g., <10 microg L(-1)) for cooking.

  4. Evaluation of digital dermoscopy in a pigmented lesion clinic: clinician versus computer assessment of malignancy risk.

    PubMed

    Boldrick, Jennifer C; Layton, Christle J; Nguyen, Josephine; Swetter, Susan M

    2007-03-01

    Digital dermoscopy systems employ computer-based algorithms to quantitate features of pigmented skin lesions (PSLs) and provide an assessment of malignancy risk. We evaluated interobserver concordance of PSL malignancy risk between a pigmented lesion specialist and an artificial neural network (ANN)-based automated digital dermoscopy system. While digital dermoscopy provides a reliable means of image capture, storage, and comparison of PSLs over time, the ANN algorithm requires further training and validation before the malignancy risk assessment feature can be widely used in clinical practice.

  5. Diagnostic validity of periapical radiography and CBCT for assessing periapical lesions that persist after endodontic surgery.

    PubMed

    Kruse, Casper; Spin-Neto, Rubens; Reibel, Jesper; Wenzel, Ann; Kirkevang, Lise-Lotte

    2017-07-14

    Traditionally, healing after surgical endodontic retreatment (SER); i.e. apicectomy with or without a retrograde filling, is assessed in periapical radiographs (PR). Recently, the use of Cone Beam CT (CBCT) has increased within endodontics. Generally, CBCT detects more periapical lesions than PR, but basic research on the true nature of these lesions is missing. The objective was to assess the diagnostic validity of PR and CBCT for determining inflammation in SER-cases that were re-operated (SER-R) due to unsuccessful healing, using histology of the periapical lesion as reference for inflammation. Records from 149 patients, receiving SER 2004-10, were screened. In total 108 patients (119 teeth) were recalled for clinical follow-up examination, PR and CBCT, of which 74 patients (83 teeth) participated. Three observers assessed PR and CBCT as "successful healing" or "unsuccessful healing" using Rud and Molven´s criteria. SER-R was offered to all non-healed teeth with expected favorable prognosis for subsequent functional retention. During SER-R, biopsy was performed and histopathology verified whether or not inflammation was present. All re-operated cases were assessed non-healed in CBCT while 11 of these were assessed successfully healed in PR. Nineteen biopsies were examined. Histopathologic diagnosis revealed 42% (teeth=8) without periapical inflammation, 16% (teeth=3) with mild inflammation, and 42% (teeth=8) with moderate to intense inflammation. A correct diagnosis was obtained in 58% with CBCT (true positives) and 63% with PR (true positives+true negatives). Of the re-operated teeth, 42% had no periapical inflammatory lesion, and hence no benefit from SER-R. Not all lesions observed in CBCT represented periapical inflammatory lesions.

  6. Assessment of simulated lesions on primary teeth with near-infrared imaging

    NASA Astrophysics Data System (ADS)

    Tam, Wilson; Lee, Robert C.; Lin, Brent; Simon, Jacob C.; Fried, Daniel

    2016-02-01

    Previous studies have demonstrated that the structural changes on enamel due to demineralization and remineralization can be exploited through optical imaging methods such as QLF, thermal and NIR imaging. The purpose of this study is to investigate whether PS-OCT and NIR reflectance imaging can be utilized to assess lesion structure in artificial enamel lesions on the smooth surfaces of primary teeth exposed to fluoride. The smooth coronal surfaces of primary teeth (n=25) were divided into 4 windows: sound, demineralization, demineralization with remineralization and APF with demineralization. Windows were treated with either acidulated phosphate fluoride (APF) for 1 minute, a demineralization solution for 4 days, and/or an acidic remineralization solution for 12 days. The samples were imaged using PS-OCT, QLF and NIR reflectance at 1400-1700 nm wavelengths. This study demonstrated that both PS-OCT and NIR reflectance imaging were suitable for assessing lesion structure in the smooth surfaces of primary dentition.

  7. Assessment of simulated lesions on primary teeth with near-infrared imaging

    PubMed Central

    Tam, Wilson; Lee, Robert C.; Lin, Brent; Simon, Jacob C.; Fried, Daniel

    2016-01-01

    Previous studies have demonstrated that the structural changes on enamel due to demineralization and remineralization can be exploited through optical imaging methods such as QLF, thermal and NIR imaging. The purpose of this study is to investigate whether PS-OCT and NIR reflectance imaging can be utilized to assess lesion structure in artificial enamel lesions on the smooth surfaces of primary teeth exposed to fluoride. The smooth coronal surfaces of primary teeth (n=25) were divided into 4 windows: sound, demineralization, demineralization with remineralization and APF with demineralization. Windows were treated with either acidulated phosphate fluoride (APF) for 1 minute, a demineralization solution for 4 days, and/or an acidic remineralization solution for 12 days. The samples were imaged using PS-OCT, QLF and NIR reflectance at 1400–1700 nm wavelengths. This study demonstrated that both PS-OCT and NIR reflectance imaging were suitable for assessing lesion structure in the smooth surfaces of primary dentition. PMID:26997743

  8. CD62-mediated activation of platelets in cerebral white matter lesions in patients with cognitive decline.

    PubMed

    Kuriyama, Nagato; Mizuno, Toshiki; Yasuike, Hiromi; Matsuno, Hiroyuki; Kawashita, Eri; Tamura, Aiko; Ozaki, Etsuko; Matsui, Daisuke; Watanabe, Isao; Koyama, Teruhide; Miyatani, Fumitaro; Kondo, Masaki; Tokuda, Takahiko; Ohshima, Youichi; Muranishi, Manabu; Akazawa, Kentaro; Takada, Akihiro; Takeda, Kazuo; Matsumoto, Sanae; Mizuno, Shigeto; Yamada, Kei; Nakagawa, Masanori; Watanabe, Yoshiyuki

    2016-01-01

    Vascular dementia is related to intracranial arteriosclerosis associated with deep white matter lesions (DWMLs). DWMLs have been linked to thrombogenesis due to sustained platelet activation; therefore, an accurate hematological marker is needed. This study was done to evaluate the usefulness of a new method to examine the function of activated platelets in order to assess DWMLs associated with cognitive decline. A total of 143 individuals (70.4 ± 6.1 years old) who underwent hospital-based health screening using head MRI were evaluated. DWLs were evaluated on T2-weighted and FLAIR images by semi-quantitatively grading them from Grade 0 (none) to Grade 3 (severe) using the Fazekas classification. Cognitive function was evaluated using the MMSE and the word fluency test. Platelet activation was assessed using fluorescence-labeled anti-human platelet monoclonal antibodies and semi-quantitatively determining PAC-1- and CD62P-positive rates by flow cytometry. Significant increases in hypertension and CD62P levels were observed with increasing DWML grade (2.6% in Group 0, 3.1% in Group 1, 4.1% in Group 2, and 5.0% in Group 3). CD62P levels were defined as elevated when they were above the mean+2SD of the Grade 0 group, and the odds ratio of the Grade 2+3 group was 3.03. A significant negative correlation was observed between CD62P levels and word fluency tests or the MMSE score. Elevations in CD62P levels, which reflect platelet function activation, were associated with white matter lesions accompanied by a decline in cognitive function. CD62P levels may be useful as a sensitive clinical marker for the early detection of DWMLs with cognitive decline. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent.

    PubMed

    Blystad, I; Håkansson, I; Tisell, A; Ernerudh, J; Smedby, Ö; Lundberg, P; Larsson, E-M

    2016-01-01

    Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions. © 2016 by American Journal of Neuroradiology.

  10. Intravoxel incoherent motion diffusion-weighted MR imaging in assessing and characterizing solitary pulmonary lesions

    PubMed Central

    Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun

    2017-01-01

    This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*. PMID:28225064

  11. Intravoxel incoherent motion diffusion-weighted MR imaging in assessing and characterizing solitary pulmonary lesions.

    PubMed

    Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun

    2017-02-22

    This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*.

  12. The Effect of Susceptibility Artifacts Related to Metallic Implants on Adjacent-Lesion Assessment in Simultaneous TOF PET/MR.

    PubMed

    Svirydenka, Hanna; Delso, Gaspar; De Galiza Barbosa, Felipe; Huellner, Martin; Davison, Helen; Fanti, Stefano; Veit-Haibach, Patrick; Ter Voert, Edwin E G W

    2017-07-01

    Metalic implants may affect attenuation correction (AC) in PET/MR imaging. The purpose of this study was to evaluate the effect of susceptibility artifacts related to metallic implants on adjacent metabolically active lesions in clinical simultaneous PET/MR scanning for both time-of-flight (TOF) and non-TOF reconstructed PET images. Methods: We included 27 patients without implants but with confirmed (18)F-FDG-avid lesions adjacent to common implant locations. In all patients, a clinically indicated whole-body (18)F-FDG PET/MR scan was acquired. Baseline non-TOF and TOF PET images were reconstructed. Reconstruction was repeated after the introduction of artificial signal voids in the AC map to simulate metallic implants in standard anatomic areas. All reconstructed images were qualitatively and quantitatively assessed and compared with the baseline images. Results: In total, 51 lesions were assessed. In 40 and 50 of these cases (non-TOF and TOF, respectively), the detectability of the lesions did not change; in 9 and 1 cases, the detectability changed; and in 2 non-TOF cases, the lesions were no longer visible after the introduction of metallic artifacts. The inclusion of TOF information significantly reduced artifacts due to simulated implants in the femoral head, sternum, and spine (P = 0.01, 0.01, and 0.03, respectively). It also improved image quality in these locations (P = 0.02, 0.01, and 0.01, respectively). The mean percentage error was -3.5% for TOF and -4.8% for non-TOF reconstructions, meaning that the inclusion of TOF information reduced the percentage error in SUVmax by 28.5% (P < 0.01). Conclusion: Qualitatively, there was a significant reduction of artifacts in the femoral head, sternum, and spine. There was also a significant qualitative improvement in image quality in these locations. Furthermore, our study indicated that simulated susceptibility artifacts related to metallic implants have a significant effect on small, moderately (18)F

  13. An in vivo experimental model to assess furcal lesions as a result of perforation.

    PubMed

    Silva, M J B; Caliari, M V; Sobrinho, A P R; Vieira, L Q; Arantes, R M E

    2009-10-01

    To design and validate a rat molar model of furcal perforation to allow investigation of the biological phenomena that follow and to explore its potential for evaluating repair materials under standardized conditions. Eighteen male Wistar rats were used. Surgical aseptic procedures were carried out in order to open the pulp chamber of a first molar tooth. A cavity was prepared on the floor of the pulp chamber using a (1/4) round bur that created a communication between the furcation and the periodontal tissues. Six animals for each time point were sacrificed on days 14, 21 and 28 to assay morphological changes at the furcation region of molars. Maxillary bone was processed, removed and sectioned. Cellular infiltration, collagen deposition and bone resorption were assessed by histological analysis. Cellularity in the lesion area was determined by morphometric analysis. Data were analysed using parametric Student's t-test. A furcal perforation model was standardized in which both radiological outcome and periodontal tissue reactions could be assessed through evaluation of cellularity, osteoclast activity and collagen deposition. The morphometric analysis revealed a greater number of cells 21 day post-surgery when compared with 14 days. This animal model was suitable for radiological and histological evaluation of the processes that accompany surgical furcal perforation.

  14. Early thalamic lesions in patients with sleep-potentiated epileptiform activity

    PubMed Central

    Sánchez Fernández, I.; Takeoka, M.; Tas, E.; Peters, J.M.; Prabhu, S.P.; Stannard, K.M.; Gregas, M.; Eksioglu, Y.; Rotenberg, A.; Riviello, J.J.; Kothare, S.V.

    2012-01-01

    Objective: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). Methods: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. Results: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). Conclusions: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA. PMID:22539569

  15. Fish biomarkers for environmental monitoring: An integrated model supporting enzyme activity and histopathological lesions

    NASA Astrophysics Data System (ADS)

    Neta, Raimunda Nonata Fortes Carvalho; Torres Junior, Audalio Rebelo

    2014-10-01

    We present a mathematical model describing the association between glutathione-S-transferase activity and brachial lesions in the catfish, Sciades herzbergii (Ariidae) from a polluted port. The catfish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in São Marcos Bay, Brazil. Two biomarkers, hepatic glutathione S-transferase (GST) activity and histopathological lesions, in gills tissue were measured. The values for GST activity were modeled with the occurrence of branchial lesions by fitting a third order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial lesions in both the wet and the dry seasons, but only at the polluted port site. The model developed in this study indicates that branchial and hepatic lesions are initiated when GST activity reaches 2.15 μmol min-1 mg protein-1. Beyond this limit, GST activity decreased to very low levels and irreversible histopathological lesions occurred. This mathematical model provides a realistic approach to analyze predictive biomarkers of environmental health status.

  16. Loss of circadian rhythmicity in body temperature and locomotor activity following suprachiasmatic lesions in the rat

    NASA Technical Reports Server (NTRS)

    Saleh, M. A.; Haro, P. J.; Winget, C. M.

    1977-01-01

    In experiments on male and female ambulatory rats, the effect of bilateral suprachiasmatic lesions on deep body temperature and locomotor activity circadian rhythms was investigated. A L/D:12/12 cycle and 23 C ambient temperature were maintained. One-half of the rats received radiofrequency lesions in the suprachiasmic nucleus (SCN) while the second group were sham operated by lowering the radiofrequency electrode to the SCN without producing electrolytic lesions. Four weeks were allowed for recuperation. Autopsies were conducted to make sure that the lesions were restricted to SCN. The results show the complete disappearance of circadian rhythm in the SCN lesioned rats and only a slight diminution for the sham operated rats.

  17. Loss of circadian rhythmicity in body temperature and locomotor activity following suprachiasmatic lesions in the rat

    NASA Technical Reports Server (NTRS)

    Saleh, M. A.; Haro, P. J.; Winget, C. M.

    1977-01-01

    In experiments on male and female ambulatory rats, the effect of bilateral suprachiasmatic lesions on deep body temperature and locomotor activity circadian rhythms was investigated. A L/D:12/12 cycle and 23 C ambient temperature were maintained. One-half of the rats received radiofrequency lesions in the suprachiasmic nucleus (SCN) while the second group were sham operated by lowering the radiofrequency electrode to the SCN without producing electrolytic lesions. Four weeks were allowed for recuperation. Autopsies were conducted to make sure that the lesions were restricted to SCN. The results show the complete disappearance of circadian rhythm in the SCN lesioned rats and only a slight diminution for the sham operated rats.

  18. A novel classification system for assessment of approximal caries lesion progression in bitewing radiographs.

    PubMed

    Senneby, Anna; Elfvin, Margareta; Stebring-Franzon, Christina; Rohlin, Madeleine

    2016-01-01

    To design and pilot a novel classification system for the assessment of caries lesion progression in bitewing radiography and to report rater agreement of the system. A classification system with drawings and text was designed to assess caries lesion progression. Guidelines for Reporting Reliability and Agreement Studies were used to study and report rater agreement. Pairs of posterior bitewing radiographs (baseline and 1-year follow-up) with different status concerning caries lesion progression were selected from files from public dental health clinics. 10 raters, 5 general dental practitioners and 5 specialists in oral and maxillofacial radiology were asked to assess the radiographs with the aid of the classification system. Seven raters repeated their assessments. Rater agreement was expressed as percentage of agreement and kappa. Kappa for the interrater agreement of 10 raters assessing progression was 0.61, indicating substantial agreement. Agreement was moderate for progression in the outer half of the dentine (kappa 0.55) and within enamel (kappa 0.44). Pairwise interrater agreement varied (range 69-92%; kappa 0.42-0.84). For about half of the pairs of raters, kappa was substantial (≥0.61). Intrarater agreement assessing progression was substantial (kappa 0.66-0.82). We demonstrated the applicability of the proposed classification system on caries lesion progression with respect to rater agreement. This system can provide a common framework for clinical decision-making on caries interventional methods and patient visiting intervals. Scientifically, this system allows for a comparative analysis of different methods of prevention and treatment of caries as well as of different caries risk assessment methods.

  19. A novel classification system for assessment of approximal caries lesion progression in bitewing radiographs

    PubMed Central

    Elfvin, Margareta; Stebring-Franzon, Christina; Rohlin, Madeleine

    2016-01-01

    Objectives: To design and pilot a novel classification system for the assessment of caries lesion progression in bitewing radiography and to report rater agreement of the system. Methods: A classification system with drawings and text was designed to assess caries lesion progression. Guidelines for Reporting Reliability and Agreement Studies were used to study and report rater agreement. Pairs of posterior bitewing radiographs (baseline and 1-year follow-up) with different status concerning caries lesion progression were selected from files from public dental health clinics. 10 raters, 5 general dental practitioners and 5 specialists in oral and maxillofacial radiology were asked to assess the radiographs with the aid of the classification system. Seven raters repeated their assessments. Rater agreement was expressed as percentage of agreement and kappa. Results: Kappa for the interrater agreement of 10 raters assessing progression was 0.61, indicating substantial agreement. Agreement was moderate for progression in the outer half of the dentine (kappa 0.55) and within enamel (kappa 0.44). Pairwise interrater agreement varied (range 69–92%; kappa 0.42–0.84). For about half of the pairs of raters, kappa was substantial (≥0.61). Intrarater agreement assessing progression was substantial (kappa 0.66–0.82). Conclusions: We demonstrated the applicability of the proposed classification system on caries lesion progression with respect to rater agreement. This system can provide a common framework for clinical decision-making on caries interventional methods and patient visiting intervals. Scientifically, this system allows for a comparative analysis of different methods of prevention and treatment of caries as well as of different caries risk assessment methods. PMID:27043978

  20. Assessment of the remineralization in simulated enamel lesions via dehydration with near-IR reflectance imaging

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel

    2015-02-01

    Previous studies have demonstrated that near-IR imaging can be used to nondestructively monitor the severity of enamel lesions. Arrested lesions typically have a highly mineralized surface layer that reduces permeability and limits diffusion into the lesion. The purpose of this study was to investigate whether the rate of water loss correlates with the degree of remineralization using near-IR reflectance imaging. Artificial bovine (n=15) enamel lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for different periods. The samples were dehydrated using an air spray for 30 seconds and surfaces were imaged using an InGaAs camera at 1300-1700 nm wavelengths. Near-IR reflectance intensity differences before and after dehydration decreased with longer periods of remineralization. This study demonstrated that near-IR reflectance imaging was suitable for the detection of remineralization in simulated caries lesions and near-IR wavelengths longer than 1400 nm are well suited for the assessment of remineralization.

  1. Assessment of the role of cone beam computed sialography in diagnosing salivary gland lesions

    PubMed Central

    Abdel-Wahed, Nagla'a; Abo-Taleb, Noha Saleh Mahmoud

    2013-01-01

    Purpose The purpose of this study was to assess cone-beam computed (CBCT) sialography imaging in the detection of different changes associated with lesions of salivary glands. Materials and Methods This study consisted of 8 cases with signs and symptoms from salivary gland lesions. Conventional sialography using digital panoramic and lateral oblique radiographs and CBCT sialography were performed for each subject. The radiographs were evaluated by 3 radiologists independently of each other. The results were compared between conventional sialography and CBCT sialography in the evaluation of various lesions associated with the salivary glands. Results There was an agreement between the radiologists in interpreting the lesions that affected salivary glands with both techniques. The detection of the presence of stones or filling defects, stenosis, ductal evagination, dilatation, and space occupying lesions was 83% for conventional sialography compared with CBCT sialography. CBCT sialography was superior to conventional sialography in revealing stones, stenosis, and strictures, especially in the second and third order branches. Conclusion It would be advisable to perform CBCT sialography in cases of obstructive salivary gland diseases for better demonstration of the ductal system of the gland. PMID:23524990

  2. Assessment of remineralization in simulated enamel lesions via dehydration with near-IR reflectance imaging.

    PubMed

    Lee, Robert C; Darling, Cynthia L; Fried, Daniel

    2015-02-24

    Previous studies have demonstrated that near-IR imaging can be used to nondestructively monitor the severity of enamel lesions. Arrested lesions typically have a highly mineralized surface layer that reduces permeability and limits diffusion into the lesion. The purpose of this study was to investigate whether the rate of water loss correlates with the degree of remineralization using near-IR reflectance imaging. Artificial bovine (n=15) enamel lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for different periods. The samples were dehydrated using an air spray for 30 seconds and surfaces were imaged using an InGaAs camera at 1300-1700 nm wavelengths. Near-IR reflectance intensity differences before and after dehydration decreased with longer periods of remineralization. This study demonstrated that near-IR reflectance imaging was suitable for the detection of remineralization in simulated caries lesions and near-IR wavelengths longer than 1400 nm are well suited for the assessment of remineralization.

  3. Straticyte demonstrates prognostic value over oral epithelial dysplasia grade for oral potentially malignant lesion assessment.

    PubMed

    Hwang, Jason T K; Gu, Ying R; Dickson, Benjamin J; Shen, Mi; Ralhan, Ranju; Walfish, Paul G; Mock, David; Pritzker, Kenneth P H

    2017-09-01

    Straticyte™ was previously shown to be a more effective prognostic assessment than the current standard of care, histopathological dysplasia grading, to assess progression risk of oral epithelial dysplasia to invasive cancer [Hwang JT, Gu YR, Shen M, Ralhan R, Walfish PG, Pritzker KP, et al. Individualized five-year risk assessment for oral premalignant lesion progression to cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:374-81]. In this follow-up study, our aim is to confirm the prognostic value of Straticyte using an independent cohort of oral biopsy cases previously assessed as epithelial dysplasia of various grades. Using Visiopharm image analysis system, we analyzed an independent retrospective cohort of 51 oral biopsy samples with known outcomes and a follow-up history of up to 12years, to verify Straticyte, an individualized 5-year risk assessment for progression of oral potentially malignant lesions to invasive squamous cell carcinoma. Straticyte classified the lesions more accurately than histopathological oral epithelial dysplasia grading for risk for progression to cancer over five years. The sensitivity of low-risk vs. non-low-risk Straticyte groups was 100% compared to 68% for mild vs. non-mild dysplasia. The sensitivity of high-risk vs. non-high-risk Straticyte was 71% compared to 3% for severe vs. non-severe dysplasia. Furthermore, the Negative Predictive Value (NPV) for Straticyte was 100% for low-risk vs. non-low-risk, whereas the NPV for mild vs. non-mild dysplasia was 38%. In this cohort, Straticyte ascertains as a more useful assessment for risk of cancer progression in oral potentially malignant lesions than oral epithelial dysplasia grade. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Ulcerogenic risk assessment of diets for pigs in relation to gastric lesion prevalence

    PubMed Central

    2013-01-01

    Background Gastric ulcers in fattening pigs from intensive pork production can cause sudden deaths on farm and the grinding intensity of the diet appears to be among the risk factors. The objective of this work is to adopt the latest laboratory tests and thresholds for the ulcerogenic risk assessment of diets from experimental reports and verify the class of risk in relation to gastric lesion prevalence in reared finishers. Results Specificity and accuracy of feed safety tests based on the ulcerogenic risk of feed associated with the particle size distribution of diets were calculated on the occurrence of gastric lesions observed at a slaughterhouse: 41 lard-type hogs, fed with two diets [pelleted (n = 21 pigs) vs. mixed meal (n = 20 pigs)], analyzed at the laboratory of our Institute, were involved. Gross inspection at the abattoir allowed the identification of the development of macroscopic gastric lesions in the pigs (13/21) fed with a pelleted complete diet, ranked in Class 1 (high ulcerogenic risk) on laboratory assessment. Breakdown of gastric lesion severity: hyperkeratosis (13/13), mucosal erosions (11/13) and bleeding ulcers (2/13). This occurrence was compared to the morphology of stomach mucosa from 20 finishers fed with a mixed meal diet, ranked in Class 3 (low ulcerogenic risk), in which no gastric lesions were observed. Very fine particle (VFP) mass (<0.4 mm) according to cut off thresholds (>36%) for the safety ranking of diets, showed: 100% positive predictive value (PPV); 100% specificity; 88.1% accuracy; 72.2% sensitivity. Conclusions Three factors emerged: the elevated mass (42.6%) of <0.4 mm particles in the pelleted complete diet confirmed the associated risk rank in Class 1 assessed by laboratory procedures, as gastric lesions were selectively observed in 61.9% of finishers fed with the high risk diet; in these animals, macroscopic gastric lesions occurred within four weeks and showed a sub-clinical course, independently of severity

  5. Quantitative assessment of multiple sclerosis lesion load using CAD and expert input

    NASA Astrophysics Data System (ADS)

    Gertych, Arkadiusz; Wong, Alexis; Sangnil, Alan; Liu, Brent J.

    2008-03-01

    Multiple sclerosis (MS) is a frequently encountered neurological disease with a progressive but variable course affecting the central nervous system. Outline-based lesion quantification in the assessment of lesion load (LL) performed on magnetic resonance (MR) images is clinically useful and provides information about the development and change reflecting overall disease burden. Methods of LL assessment that rely on human input are tedious, have higher intra- and inter-observer variability and are more time-consuming than computerized automatic (CAD) techniques. At present it seems that methods based on human lesion identification preceded by non-interactive outlining by CAD are the best LL quantification strategies. We have developed a CAD that automatically quantifies MS lesions, displays 3-D lesion map and appends radiological findings to original images according to current DICOM standard. CAD is also capable to display and track changes and make comparison between patient's separate MRI studies to determine disease progression. The findings are exported to a separate imaging tool for review and final approval by expert. Capturing and standardized archiving of manual contours is also implemented. Similarity coefficients calculated from quantities of LL in collected exams show a good correlation of CAD-derived results vs. those incorporated as expert's reading. Combining the CAD approach with an expert interaction may impact to the diagnostic work-up of MS patients because of improved reproducibility in LL assessment and reduced time for single MR or comparative exams reading. Inclusion of CAD-generated outlines as DICOM-compliant overlays into the image data can serve as a better reference in MS progression tracking.

  6. Activation of calpain-1 in human carotid artery atherosclerotic lesions

    PubMed Central

    Gonçalves, Isabel; Nitulescu, Mihaela; Saido, Takaomi C; Dias, Nuno; Pedro, Luis M; e Fernandes, José Fernandes; Ares, Mikko PS; Pörn-Ares, Isabella

    2009-01-01

    Background In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. Methods Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed α-fodrin was used on western blots. Results We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. Conclusion These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms. PMID:19538725

  7. Image coregistration: quantitative processing framework for the assessment of brain lesions.

    PubMed

    Huhdanpaa, Hannu; Hwang, Darryl H; Gasparian, Gregory G; Booker, Michael T; Cen, Yong; Lerner, Alexander; Boyko, Orest B; Go, John L; Kim, Paul E; Rajamohan, Anandh; Law, Meng; Shiroishi, Mark S

    2014-06-01

    The quantitative, multiparametric assessment of brain lesions requires coregistering different parameters derived from MRI sequences. This will be followed by analysis of the voxel values of the ROI within the sequences and calculated parametric maps, and deriving multiparametric models to classify imaging data. There is a need for an intuitive, automated quantitative processing framework that is generalized and adaptable to different clinical and research questions. As such flexible frameworks have not been previously described, we proceeded to construct a quantitative post-processing framework with commonly available software components. Matlab was chosen as the programming/integration environment, and SPM was chosen as the coregistration component. Matlab routines were created to extract and concatenate the coregistration transforms, take the coregistered MRI sequences as inputs to the process, allow specification of the ROI, and store the voxel values to the database for statistical analysis. The functionality of the framework was validated using brain tumor MRI cases. The implementation of this quantitative post-processing framework enables intuitive creation of multiple parameters for each voxel, facilitating near real-time in-depth voxel-wise analysis. Our initial empirical evaluation of the framework is an increased usage of analysis requiring post-processing and increased number of simultaneous research activities by clinicians and researchers with non-technical backgrounds. We show that common software components can be utilized to implement an intuitive real-time quantitative post-processing framework, resulting in improved scalability and increased adoption of post-processing needed to answer important diagnostic questions.

  8. Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

    PubMed Central

    Fuentes-Duculan, Judilyn; Moussai, Dariush; Gulati, Nicholas; Sullivan-Whalen, Mary; Gilleaudeau, Patricia; Cohen, Jules A.; Krueger, James G.

    2011-01-01

    Background Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. Methodology/Principal Findings In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo. Conclusions/Significance These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses. PMID:21541348

  9. Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions

    PubMed Central

    1990-01-01

    The major characteristics of human atherosclerotic lesions are similar to those of a chronic inflammatory reaction, namely fibrosis, mesenchymal cell proliferation, the presence of resident macrophages, and cell necrosis. Atherosclerosis exhibits in addition the feature of lipid (mainly cholesterol) accumulation. The results of the present report demonstrate that a specific cholesterol-containing lipid particle present in human atherosclerotic lesions activates the complement system to completion. Thus, lipid could represent a stimulatory factor for the inflammatory reaction, whose underlying mechanistic basis may be, at least in part, complement activation. The complement-activating lipid was purified from saline extracts of aortic atherosclerotic lesions by sucrose density gradient centrifugation followed by molecular sieve chromatography on Sepharose 2B. It contained little protein other than albumin, was 100-500 nm in size, exhibited an unesterified to total cholesterol ratio of 0.58 and an unesterified cholesterol to phospholipid ratio of 1.2. The lipid, termed lesion lipid complement (LCA), activated the alternative pathway of complement in a dose-dependent manner. Lesion-extracted low density lipoprotein (LDL) obtained during the purification procedure failed to activate complement. Specific generation of C3a desArg and C5b-9 by LCA indicated C3/C5 convertase formation with activation proceeding to completion. Biochemical and electron microscopic evaluations revealed that much of the C5b-9 present in atherosclerotic lesions is membraneous, rather than fluid phase SC5b-9. The observations reported herein establish a link between lipid insudation and inflammation in atherosclerotic lesions via the mechanism of complement activation. PMID:2373993

  10. Added value of Virtual Touch IQ shear wave elastography in the ultrasound assessment of breast lesions.

    PubMed

    Ianculescu, Victor; Ciolovan, Laura Maria; Dunant, Ariane; Vielh, Philippe; Mazouni, Chafika; Delaloge, Suzette; Dromain, Clarisse; Blidaru, Alexandru; Balleyguier, Corinne

    2014-05-01

    To determine the diagnostic performance of Acoustic Radiation Force Impulse (ARFI) Virtual Touch IQ shear wave elastography in the discrimination of benign and malignant breast lesions. Conventional B-mode and elasticity imaging were used to evaluate 110 breast lesions. Elastographic assessment of breast tissue abnormalities was done using a shear wave based technique, Virtual Touch IQ (VTIQ), implemented on a Siemens Acuson S3000 ultrasound machine. Tissue mechanical properties were interpreted as two-dimensional qualitative and quantitative colour maps displaying relative shear wave velocity. Wave speed measurements in m/s were possible at operator defined regions of interest. The pathologic diagnosis was established on samples obtained by ultrasound guided core biopsy or fine needle aspiration. BIRADS based B-mode evaluation of the 48 benign and 62 malignant lesions achieved 92% sensitivity and 62.5% specificity. Subsequently performed VTIQ elastography relying on visual interpretation of the colour overlay displaying relative shear wave velocities managed similar standalone diagnostic performance with 92% sensitivity and 64.6% specificity. Lesion and surrounding tissue shear wave speed values were calculated and a significant difference was found between the benign and malignant populations (Mann-Whitney U test, p<0.0001). By selecting a lesion cut-off value of 3.31m/s we achieved 80.4% sensitivity and 73% specificity. Applying this threshold only to BIRADS 4a masses, we reached overall levels of 92% sensitivity and 72.9% specificity. VTIQ qualitative and quantitative elastography has the potential to further characterise B-mode detected breast lesions, increasing specificity and reducing the number of unnecessary biopsies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  12. Neuroprotective activity of thioctic acid in central nervous system lesions consequent to peripheral nerve injury.

    PubMed

    Tomassoni, Daniele; Amenta, Francesco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Nwankwo, Innocent E; Pacini, Alessandra; Tayebati, Seyed Khosrow

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/-)-, (+)-, or (-)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/-)- or (-)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies.

  13. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

  14. Spinal neuropeptide modulation, functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis.

    PubMed

    Otis, Colombe; Guillot, Martin; Moreau, Maxim; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Beaudry, Francis; Troncy, Eric

    2017-04-24

    Characterising the temporal evolution of changes observed in pain functional assessment, spinal neuropeptides and cartilage lesions of the joint after chemical osteoarthritis (OA) induction in rats. On day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA). Rats receiving 2mg MIA were temporally assessed at D3, D7, D14 and D21 for the total spinal cord concentration of substance P (SP), calcitonin gene related-peptide (CGRP), bradykinin (BK) and somatostatin (STT), and for severity of cartilage lesions. At D21, the same outcomes were compared with the IA 1mg MIA, IA 2mg MIA associated with punctual IA injection of lidocaine at D7, D14 and D21, sham (sterile saline) and naïve groups. Tactile allodynia was sequentially assessed using a von Frey anaesthesiometer. Non-parametric and mixed models were applied for statistical analysis. Tactile allodynia developed in the 2mg MIA group as soon as D3 and was maintained up to D21. Punctual IA treatment with lidocaine counteracted it at D7 and D14. Compared to naïve, [STT], [BK] and [CGRP] reached a maximum as early as D7, which plateaued up to D21. For [SP], the increase was delayed up to D14 and maintained at D21. No difference in levels of neuropeptides was observed between MIA doses, except for higher [STT] in the 2mg MIA group (P=0.029). Neuropeptides SP and BK were responsive to lidocaine treatment. The increase in severity of cartilage lesions was significant only in the 2mg MIA groups (P=0.01). In the MIA OA pain model, neuropeptide modulation appears early, and confirms the central nervous system to be an attractive target for OA pain quantification. The relationship of neuropeptide release with severity of cartilage lesions and functional assessment are promising and need further validation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Oral health-related knowledge, attitudes, behavior, and family characteristics among Finnish schoolchildren with and without active initial caries lesions.

    PubMed

    Poutanen, Raija; Lahti, Satu; Seppä, Liisa; Tolvanen, Mimmi; Hausen, Hannu

    2007-04-01

    The aim of this study was to determine whether the presence of active initial caries lesions among 11 to 12-year-old schoolchildren is associated with parental and child-related factors and whether there are gender differences in these associations. The data were gathered by questionnaires from children and their parents, who replied without knowing the other's answers. All the children were invited to participate in a screening for the presence or absence of active initial caries lesions. Factors associated with children's initial caries were studied with logistic regression analyses. The parents' self-assessed poor dental health, the parents' and the child's poor oral health-related behavior, and the child's response "I don't know" to the question concerning his/her parents' possible dental caries were associated with the presence of active initial caries lesions. The results of logistic regression analyses were different between girls and boys. Among the girls, many parent-related factors were associated with the presence of initial caries. Among the boys, most factors were related to the child; and of the parent-related factors, only parents' poor self-assessed dental health was associated with initial caries; the effect was modified by the father's occupational level. Parental factors affect boys' and girls' dental health differently. Among boys, the effect of the fathers was seen as the father's occupational level; among girls, parental knowledge and behavior were important. When school interventions to promote health are planned, the important role of the parents should be emphasized.

  16. Circadian distribution of motor-activity in unilaterally 6-hydroxy-dopamine lesioned rats.

    PubMed

    Baier, Paul Christian; Branisa, Pablo; Koch, Reinhard; Schindehütte, Jan; Paulus, Walter; Trenkwalder, Claudia

    2006-02-01

    Sleep abnormalities in idiopathic Parkinson's disease (PD) frequently consist in a reduction of total sleep time and efficacy and subsequent excessive daytime sleepiness. As it remains unclear whether these phenomena are part of the disease itself or result from pharmacological treatment, animal models for investigating the pathophysiology of sleep alterations in PD may add knowledge to this research area. In the present study, we investigate whether changes in circadian motor activity occur in 6-OHDA-lesioning model for PD, and allow a screening for disturbed sleep-waking behaviour. Activity measurements of six male Wistar rats with 6-OHDA-lesions in the medial forebrain bundle and six controls were carried out in two consecutive 12:12 h light-dark (LD) cycles. A computer-based video-analysis system, recording the animals' movement tracks was used. Distance travelled and number of transitions between movement periods and resting periods were determined. Although 6-OHDA-lesioned animals show a reduced locomotor activity compared to non-lesioned rats, the circadian distribution basically remained intact. However, some lesioning effects were more pronounced in the resting phase than in the activity phase, possibly paralleling nocturnal akinesia in PD. In order to further elucidate the described phenomena, it will be necessary to perform studies combining sleep recordings with locomotor activity measurements.

  17. BIRDSHOT CHORIORETINITIS LESIONS ON INDOCYANINE GREEN ANGIOGRAPHY AS AN INDICATOR OF DISEASE ACTIVITY.

    PubMed

    Cao, Jennifer H; Silpa-Archa, Sukhum; Freitas-Neto, Clovis A; Foster, C Stephen

    2016-09-01

    To determine whether classical indocyanine green angiography lesions in patients with birdshot chorioretinitis can be used to monitor disease activity. A retrospective case series was performed on 26 eyes in 26 consecutive patients with birdshot chorioretinitis who had at least one indocyanine green angiography performed during disease activity and another during disease quiescence. Using Photoshop, the mean number, area, and area per spot on indocyanine green angiography were compared between disease activity and quiescence using a paired ratio test. The mean total lesion number, area, and area per spot during disease activity were 75.27 spots, 24,525 pixels, and 364 pixels/spots, respectively. The mean total lesion number, area, and area per spot size during disease quiescence were 28.35 spots (P < 0.01), 7,411 pixels (P < 0.01), and 279 pixels/spot (P = 0.12), respectively. There was a statistically significant decrease in the mean total area and number of lesions between the time of disease activity and disease quiescence (P < 0.01). Our results suggest that indocyanine green angiography has a role not only in diagnosis but also in monitoring treatment effectiveness; lesions can be reversible with treatment and their reappearance may be an indicator of disease relapse.

  18. Simulation and assessment of realistic breast lesions using fractal growth models

    NASA Astrophysics Data System (ADS)

    Rashidnasab, A.; Elangovan, P.; Yip, M.; Diaz, O.; Dance, D. R.; Young, K. C.; Wells, K.

    2013-08-01

    A new method of generating realistic three dimensional simulated breast lesions known as diffusion limited aggregation (DLA) is presented, and compared with the random walk (RW) method. Both methods of lesion simulation utilize a physics-based method for inserting these simulated lesions into 2D clinical mammogram images that takes into account the polychromatic x-ray spectrum, local glandularity and scatter. DLA and RW masses were assessed for realism via a receiver operating characteristic (ROC) study with nine observers. The study comprised 150 images of which 50 were real pathology proven mammograms, 50 were normal mammograms with RW inserted masses and 50 were normal mammograms with DLA inserted masses. The average area under the ROC curve for the DLA method was 0.55 (95% confidence interval 0.51-0.59) compared to 0.60 (95% confidence interval 0.56-0.63) for the RW method. The observer study results suggest that the DLA method produced more realistic masses with more variability in shape compared to the RW method. DLA generated lesions can overcome the lack of complexity in structure and shape in many current methods of mass simulation.

  19. Nuclear Receptor Activity and Liver Cancer Lesion Progression

    EPA Science Inventory

    Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. We explored this question using human CAR, PXR, PPARα,...

  20. Assessment of exercise-induced minor muscle lesions: the accuracy of Cyriax's diagnosis by selective tension paradigm.

    PubMed

    Franklin, M E; Conner-Kerr, T; Chamness, M; Chenier, T C; Kelly, R R; Hodge, T

    1996-09-01

    The Cyriax selective tension assessment paradigm is commonly used by clinicians for the diagnosis of soft tissue lesions; however, studies have not demonstrated that it is a valid method. The purpose of this study was to examine the construct validity of the active motion, passive motion, resisted movement, and palpation components of the Cyriax selective tension diagnosis paradigm in subjects with an exercise-induced minor hamstring muscle lesion. Nine female subjects with a mean age of 23.6 years (SD = 4.7) and a mass of 57.3 kg (SD = 10.7) performed two sets of 20 maximal eccentric isokinetic knee flexor contractions designed to induce a minor muscle lesion of the hamstrings. Active range of motion, passive range of motion, knee extension end-feel pain relative to resistance sequence, knee flexor isometric strength, pain perception during knee flexor resisted movement testing, and palpation pain of the hamstrings were assessed at 0, 5, 2, 12, 24, 48, and 72 hours postexercise and compared with Cyriax's hypothesized selective tension paradigm results. Consistent with Cyriax's paradigm, passive range of motion remained unchanged, and perceived pain of the hamstrings increased with resistance testing at 12, 24, 48, and 72 hours postexercise when compared with baseline. In addition, palpation pain of the hamstrings was significantly elevated at 48 and 72 hours after exercise (p < 0.05). In contrast of Cyriax's paradigm, active range of motion was significantly reduced over time (p < 0.05), with the least amount of motion compared to baseline (85%) occurring at 48 hours postexercise. Further, resisted movement testing found significant knee flexor isometric strength reductions over time (p < 0.05), with the greatest reductions (33%) occurring at 48 hours postexercise. According to Cyriax, when a minor muscle lesion is tested, it should be strong and painful; however, none of the postexercise time frames exhibited results that were strong and painful. This study

  1. Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

    PubMed Central

    Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

    2014-01-01

    Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr−/−Apob 100/100 Mttp flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

  2. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.

    PubMed

    Björkegren, Johan L M; Hägg, Sara; Talukdar, Husain A; Foroughi Asl, Hassan; Jain, Rajeev K; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

    2014-02-01

    Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-)Apob (100/100) Mttp (flox/flox)Mx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions.

  3. Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli.

    PubMed

    Hilz, Max J; Devinsky, Orrin; Szczepanska, Hanna; Borod, Joan C; Marthol, Harald; Tutaj, Marcin

    2006-12-01

    Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 +/- 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 +/- 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 +/- 11.6 years), we monitored HR as R-R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR

  4. Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

    PubMed

    Strassner, James P; Rashighi, Mehdi; Ahmed Refat, Maggi; Richmond, Jillian M; Harris, John E

    2017-05-01

    Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects. Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. In screening and validation, CD8(+) T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3. A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response. Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Hippocampus and two-way active avoidance conditioning: Contrasting effects of cytotoxic lesion and temporary inactivation.

    PubMed

    Wang, Jia; Bast, Tobias; Wang, Yu-Cong; Zhang, Wei-Ning

    2015-12-01

    Hippocampal lesions tend to facilitate two-way active avoidance (2WAA) conditioning, where rats learn to cross to the opposite side of a conditioning chamber to avoid a tone-signaled footshock. This classical finding has been suggested to reflect that hippocampus-dependent place/context memory inhibits 2WAA (a crossing response to the opposite side is inhibited by the memory that this is the place where a shock was received on the previous trial). However, more recent research suggests other aspects of hippocampal function that may support 2WAA learning. More specifically, the ventral hippocampus has been shown to contribute to behavioral responses to aversive stimuli and to positively modulate the meso-accumbens dopamine system, whose activation has been implicated in 2WAA learning. Permanent hippocampal lesions may not reveal these contributions because, following complete and permanent loss of hippocampal output, other brain regions may mediate these processes or because deficits could be masked by lesion-induced extra-hippocampal changes, including an upregulation of accumbal dopamine transmission. Here, we re-examined the hippocampal role in 2WAA learning in Wistar rats, using permanent NMDA-induced neurotoxic lesions and temporary functional inhibition by muscimol or tetrodotoxin (TTX) infusion. Complete hippocampal lesions tended to facilitate 2WAA learning, whereas ventral (VH) or dorsal hippocampal (DH) lesions had no effect. In contrast, VH or DH muscimol or TTX infusions impaired 2WAA learning. Ventral infusions caused an immediate impairment, whereas after dorsal infusions rats showed intact 2WAA learning for 40-50 min, before a marked deficit emerged. These data show that functional inhibition of ventral hippocampus disrupts 2WAA learning, while the delayed impairment following dorsal infusions may reflect the time required for drug diffusion to ventral hippocampus. Overall, using temporary functional inhibition, our study shows that the ventral

  6. Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by activated p21-activated kinase-1 protects keratinocytes in UV-B-induced premalignant skin lesions.

    PubMed

    Beesetti, S; Mavuluri, J; Surabhi, R P; Oberyszyn, T M; Tober, K; Pitani, R S; Joseph, L D; Venkatraman, G; Rayala, S K

    2017-07-10

    Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry. Further, we observed that phospho-Pak1 and Pak1 levels are high in UV-B-exposed hairless SKH mouse model skin samples as compared with unexposed skin tissue. Our results from cell line and animal models showed that Pak1 is activated in response to UV-B radiation, and this activated Pak1 translocates from the cytoplasm to the nucleus. Inside the nucleus, Pak1 via C-Fos binds to a specific promoter region of DNA repair kinase ATR (ataxia-telangiectasia and Rad3-related protein) and acts as a transcriptional regulator of ATR. Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR. To our knowledge, this is the first study that evaluates the functional and clinical significance of a signaling molecule, Pak1, in sun-induced premalignant skin lesions and indicates that increased Pak1 activation and expression could serve as an early warning sign of progression toward non-melanoma skin cancer, if ignored.Oncogene advance online publication, 10 July 2017; doi:10.1038/onc.2017.218.

  7. Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

    PubMed Central

    2010-01-01

    Background The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the non-injured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases PMID:20184752

  8. A Weibull-PBPK model for assessing risk of arsenic-induced skin lesions in children.

    PubMed

    Liao, Chung-Min; Lin, Tzu-Ling; Chen, Szu-Chieh

    2008-03-25

    Chronic arsenic exposure and skin lesions (keratosis and hyperpigmentation) are inextricably linked. This paper was to quantify the children skin lesions risks and to further recommend safe drinking water arsenic standard based on reported arsenic epidemiological data. We linked the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate safe drinking water arsenic concentrations and to perform the risk characterization. We calculated odds ratios (ORs) to assess the relative magnitude of the effect of the arsenic exposure on the likelihood of the prevalence of children skin lesions by calculating proposed Weibull-based prevalence ratios of exposed to control groups associated with the age group-specific PBPK model predicted dimethylarsinite (MMA(III)) levels in urine. Positive relationships between arsenic exposures and cumulative prevalence ratios of skin lesions were found using Weibull dose-response model (r2=0.91-0.96). We reported that the safe drinking water arsenic standards were recommended to be 2.2 and 1 microg/L for male and 6 and 2.8 microg/L for female in 0-6 and 7-18 years age groups, respectively, based on hyperpigmentation with an excess risk of 10(-3) for a 75 years lifetime exposure. Risk predictions indicate that estimated ORs have 95% confidence intervals of 1.33-5.12, 1.74-19.15, and 2.81-19.27 based on mean drinking water arsenic contents of 283.19, 282.65, and 468.81 microg/L, respectively, in West Bengal, India, Bangladesh, and southwestern Taiwan. Our findings also suggest that increasing urinary monomethylarsonic acid (MMA) levels are associated with an increase in risks of arsenic-induced children skin lesions.

  9. The natural course of active choroidal lesions in the presumed ocular histoplasmosis syndrome.

    PubMed Central

    Gutman, F A

    1979-01-01

    Eighty-two patients and 106 eyes with the POHS have been followed for one year or longer. Untreated active choroidal lesions were divided into groupings based on the distance from the center of the CFZ and the reltionship to the border of the CFZ. Twenty-three percent of untreated active choroidal lesions that were located inside the CFZ achieved 20/20 to 20/40 vision. Sixty-three percent of untreated active choroidal lesions that were located outside of the CFZ achieved a vision of 20/20 to 20/40. The active choroidal lesions with the best visual prognosis were 0.25 to 0.5 disc diamterers, demonstrated no growth, and had little or no associated choroidal bleeding. Activation of choroidal lesions in the fellow eye at the site of preexisting atrophic scars was documented in 21% of the eyes. One fellow eye developed a de novo active choroidal lesion. Eighteen percent of the cases had structurally congested nerve heads characterized by slight elevation of the disc and no physiologic depression; 3% of the eyes had drusen of the optic nerve. A relationship may exist between peripapillary scarring in the POHS and these nerve head changes. Images FIGURE 4 E FIGURE 4 F FIGURE 4 G FIGURE 4 H FIGURE 4 I FIGURE 4 J FIGURE 4 K FIGURE 4 L FIGURE 3 A FIGURE 3 B FIGURE 3 C FIGURE 4 A FIGURE 4 B FIGURE 4 C FIGURE 4 D FIGURE 5 A FIGURE 5 B FIGURE 5 C FIGURE 6 A FIGURE 6 B FIGURE 6 C FIGURE 7 A FIGURE 7 B FIGURE 7 C FIGURE 7 D FIGURE 7 E FIGURE 8 A FIGURE 8 B FIGURE 8 C FIGURE 8 D FIGURE 9 A FIGURE 9 B FIGURE 9 C FIGURE 9 D FIGURE 10 A FIGURE 10 B FIGURE 10 C FIGURE 10 D PMID:397662

  10. Visual assessment of magnetic resonance imaging perfusion lesions in a large patient group.

    PubMed

    Siemonsen, S; Fitting, T; Thomalla, G; Krützelmann, A; Fiehler, J

    2012-12-01

    Few magnetic resonance imaging (MRI) studies of stroke have evaluated the value of visual assessment of perfusion/diffusion mismatch, which is crucial for routine application. In this study an attempt was made to visually assess perfusion lesions resembling the acute clinical situation and identify parameters with the highest interobserver reliability when used to define a perfusion/diffusion mismatch and the highest accuracy for prediction of infarct growth. Magnetic resonance imaging was performed within 6 h of symptom onset and again 1-11 days thereafter in 86 consecutive stroke patients who received intravenous thrombolytic therapy. The MRI protocol included diffusion-weighted imaging apparent diffusion coefficient (DWI/ADC), fluid-attenuated inversion recovery (FLAIR) and perfusion imaging (PI). Maps for different perfusion parameters, e.g. cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were calculated. Areas of perfusion deficits of all perfusion parameters were visually compared to corresponding ADCs and final infarct size by two independent observers. The final infarct size was overestimated by TTP (in 81/83 patients by raters 1 and 2, respectively), MTT (82/83) and CBF (65/74) lesions. The ADC lesions were rated smaller than the final infarct size in 43/38 cases by raters 1 and 2 and the CBV decrease was rated to underestimate final infarct size in 40/31 cases. The only significantly increased OR of 3.883 (95 % CI 1.466-10.819, p = 0.004, rater 1)/5.142 (95 % CI 1.828-15.142, p = 0.001, rater 2) for predicting infarct growth was observed for the presence of a CBV > ADC mismatch, which also showed the highest kappa value of 0.407. All mismatch patterns were prone to high interrater variability when assessed under conditions resembling the clinical setting. Of all tested mismatch patterns the CBV > ADC mismatch was the strongest predictor of lesion growth while visual assessment of TTP and CBF generally

  11. Systemic right-to-left shunts, ischemic brain lesions, and persistent migraine activity.

    PubMed

    Koppen, Hille; Palm-Meinders, Inge H; Mess, Werner H; Keunen, Ruud W; Terwindt, Gisela M; Launer, Lenore J; van Buchem, Mark A; Kruit, Mark C; Ferrari, Michel D

    2016-05-03

    To assess whether migraine in the general population is associated with increased risk of systemic right-to-left shunts (RLS) and whether RLS are associated with increased prevalence of brain infarcts and persistent recurrence of migraine attacks at older age. Brain MRI and transcranial Doppler with air contrast in 166 unselected migraineurs (mean age ± SD 56 ± 7.7 years; 70% women; n = 96 migraine with aura) and 69 controls (mean age ± SD 55 ± 7.6 years; 65% women) from the general population. Participants with migraine with aura more frequently had Valsalva-induced RLS (60%), in particular large-sized, compared to controls (42%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.1-3.9; p = 0.02) and participants with migraine without aura (40%; OR 2.3; 95% CI 1.2-4.3; p = 0.01). They also more frequently had spontaneous RLS (35%) than participants with migraine without aura (17%; OR 2.6; 95% CI 1.3-5.6; p = 0.01) but not compared to controls (26%; OR 1.6; 95% CI 0.8-3.1; p = 0.2). Participants with migraine with aura and spontaneous RLS more frequently had persistent migraine activity (85%) than participants with migraine without spontaneous RLS (63%; OR 3.4; 95% CI 1.2-10.1; p = 0.03). Nine percent of participants with RLS had silent posterior circulation infarcts compared to 3% of participants without RLS (OR 2.8; 95% CI 0.9-9.3; p = 0.08), independent of migraine status. RLS were not associated with white matter lesions. RLS are more prevalent in migraineurs with aura but do not explain the increased prevalence of silent posterior circulation infarcts or white matter lesions in migraineurs. Spontaneous RLS are associated with persistent migraine. © 2016 American Academy of Neurology.

  12. Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions.

    PubMed

    Anbar, Tag; Zuel-Fakkar, Nehal Mohamed; Matta, Mary Fikry; Arbab, Mai Mohammed Ibrahim

    2016-01-01

    Vitiligo is the most prevalent acquired pigmentary disorder as a result of destruction of melanocytes. Several studies have reported increased serum levels of homocysteine (Hcy) in vitiligo patients which may be the result of decreased Vitamin B12 and folic acid levels. In addition, homocystinuria is associated with pigmentary dilution. On the other hand, other studies reported normal serum homocysteine levels. Our aim was to study the Hcy level in active vitiligo patients both in serum and in suction blister fluid obtained from the lesional skin. A total of 30 patients with active vitiligo of both sexes and 30 healthy volunteers were enrolled in this study. Sera from the blood and from lesional induced bullae were obtained from the patients and controls and were assayed for Hcy by enzyme-linked immunosorbent assay (ELISA). The collected data were analyzed by SPSS version 17. There were no significant differences in the serum levels of Hcy between patients and healthy controls, however, the increase in Hcy level was highly statistically significant in the patients' lesional induced bulla compared to the healthy controls. There was no significant difference in Hcy levels between males and females and between patients with negative or positive family histories of vitiligo. The presence of a high homocysteine level in active vitiligo lesions points to a local event occurring in this lesion, which is not reflected as an increase in the patient's serum level.

  13. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

    PubMed

    Plumb, Jonnie; McQuaid, Stephen; Mirakhur, Meenakshi; Kirk, John

    2002-04-01

    Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy.

  14. Ladder Treadmill: A Method to Assess Locomotion in Cats with an Intact or Lesioned Spinal Cord.

    PubMed

    Escalona, Manuel; Delivet-Mongrain, Hugo; Kundu, Aritra; Gossard, Jean-Pierre; Rossignol, Serge

    2017-05-31

    After lesions of the CNS, locomotor abilities of animals (mainly cats) are often assessed on a simple flat treadmill (FTM), which imposes little demands on supraspinal structures as is the case when walking on targets. Therefore, the aims of the present work were as follows: (1) to develop a treadmill allowing the assessment of locomotion of intact cats required to place the paws on the rungs of a moving ladder treadmill (LTM); (2) to assess the capability of cats after a unilateral spinal hemisection at T10 to cope with such a demanding locomotor task; and (3) to regularly train cats for 6 weeks on the LTM to determine whether such regular training improves locomotor recovery on the FTM. A significant improvement would indicate that LTM training maximizes the contribution of spinal locomotor circuits as well as remnant supraspinal inputs. Together, we used 9 cats (7 females, 2 males). Six were used to compare the EMG and kinematic locomotor characteristics during walking on the FTM and LTM. We found that the swing phase during LTM walking was slightly enhanced as well as some specific activity of knee flexor muscles. Fore-hindlimb coupling favored a more stable diagonal coupling. These 6 cats were then hemispinalized and trained for 6 weeks on the LTM, whereas the 3 other cats were hemispinalized and trained solely on the FTM to compare the two training regimens. Intensive LTM training after hemisection was found to change features of locomotion, such as the foot trajectory as well as diminished paw drag often observed after hemisection.SIGNIFICANCE STATEMENT This paper introduces a method (ladder treadmill [LTM]) to study the locomotor ability of cats with an intact spinal cord or after a unilateral hemisection to walk with a precise foot placement on the rungs fixed to an ordinary flat treadmill (FTM). Because cats are compared in various conditions (intact or hemisected at different time points) in the same enclosure on the FTM and the LTM, the changes in

  15. Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions.

    PubMed

    Olivry, Thierry; Mayhew, David; Paps, Judy S; Linder, Keith E; Peredo, Carlos; Rajpal, Deepak; Hofland, Hans; Cote-Sierra, Javier

    2016-10-01

    Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Automatic coronary lumen segmentation with partial volume modeling improves lesions' hemodynamic significance assessment

    NASA Astrophysics Data System (ADS)

    Freiman, M.; Lamash, Y.; Gilboa, G.; Nickisch, H.; Prevrhal, S.; Schmitt, H.; Vembar, M.; Goshen, L.

    2016-03-01

    The determination of hemodynamic significance of coronary artery lesions from cardiac computed tomography angiography (CCTA) based on blood flow simulations has the potential to improve CCTA's specificity, thus resulting in improved clinical decision making. Accurate coronary lumen segmentation required for flow simulation is challenging due to several factors. Specifically, the partial-volume effect (PVE) in small-diameter lumina may result in overestimation of the lumen diameter that can lead to an erroneous hemodynamic significance assessment. In this work, we present a coronary artery segmentation algorithm tailored specifically for flow simulations by accounting for the PVE. Our algorithm detects lumen regions that may be subject to the PVE by analyzing the intensity values along the coronary centerline and integrates this information into a machine-learning based graph min-cut segmentation framework to obtain accurate coronary lumen segmentations. We demonstrate the improvement in hemodynamic significance assessment achieved by accounting for the PVE in the automatic segmentation of 91 coronary artery lesions from 85 patients. We compare hemodynamic significance assessments by means of fractional flow reserve (FFR) resulting from simulations on 3D models generated by our segmentation algorithm with and without accounting for the PVE. By accounting for the PVE we improved the area under the ROC curve for detecting hemodynamically significant CAD by 29% (N=91, 0.85 vs. 0.66, p<0.05, Delong's test) with invasive FFR threshold of 0.8 as the reference standard. Our algorithm has the potential to facilitate non-invasive hemodynamic significance assessment of coronary lesions.

  17. [Telomerase activity in esophageal carcinoma and lesions unstained with Lugol's solution].

    PubMed

    Yoneyama, K; Aoyama, N; Koizumi, H; Tamai, S

    1998-05-01

    Telomerase is a specific enzyme required for the replication of telomeres. Its activity is detected in almost human cancers. We examined in esophageal carcinoma and lesions unstained with Lugol's solution telomerase activity by using telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detected in all 22 esophageal carcinomas, regardless of histopathological findings. In unstained lesions, telomerase activity was detected in 15 of 22; 10 squamous cell carcinomas, four dysplasia, one regenerative epithelium, no telomerase activity was found in seven; four normal esophageal epithelia, two Barrett's esophagi, one regenerative epithelium. These results suggest that telomerase activity may be a useful molecular marker for the diagnosis of esophageal carcinoma and of the early esophageal carcinoma in area unstained with Lugol's solution.

  18. A 20-year study of dentists' and dental hygienists' assessment of dental caries lesions in bite-wing radiographs.

    PubMed

    Gabre, Pia; Birring, Eva; Gahnberg, Lars

    2006-01-01

    Epidemiological data reveal that the prevalence of dental caries in western countries has decreased in recent decades. The aim of this study was to investigate how dentists and dental hygienists assess dental caries lesions in bite-wing radiographs between 1983 and 2003. All dentists and dental hygienists in Public Dental Health in Uppsala County were offered to take part in the study. The participants assessed manifest and initial caries lesions in eight bite-wing radiographs from three patients individually. An X-ray viewer and binoculars were used. The assessments were repeated in the same radiographs every five years, a total of five times, between 1983 and 2003. In the different test occasions 80-103 dentists and 11-48 dental hygienists participated. The registration of dental caries changed between 1983 and 2003. The number of manifest lesions registered by dentists decreased between 1983 and 1988, but were stable after 1988. Dental hygienists showed no changes in the registration of manifest lesions during the study. Initial lesions registered by dentists and dental hygienists increased between 1988 and 1998. Assessments of initial caries lesions displayed a wider range than manifest lesions. Increasing age and more years in the profession resulted in fewer registered initial caries lesions. Dental hygienists had a tendency to register less caries than dentists. In conclusion, the result of the study indicate that inclusion of initial caries lesions in epidemiological reports should lead to a reduction in reliability. The changes in assessments of manifest caries lesions that took place in the 19805s should be considered when epidemiological data are evaluated.

  19. Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells

    PubMed Central

    JOHNSON, SARA D.; LEVINGSTON, CORINNE; YOUNG, M. RITA I.

    2016-01-01

    Background Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. Materials and Methods A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. Results Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4+ T cell expression of the IL-2 receptor CD25 and CD8+ T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell-conditioned media or media alone. Conclusion Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. PMID:27354582

  20. Energy assessment: physical activity

    USDA-ARS?s Scientific Manuscript database

    Physical activity is an important component of total energy expenditure, contributing to energy intake needs; it also provides certain health benefits. This review chapter provides state-of-the-art information to researchers and clinicians who are interested in developing research studies or interv...

  1. Design and characterization of a handheld multimodal imaging device for the assessment of oral epithelial lesions

    NASA Astrophysics Data System (ADS)

    Higgins, Laura M.; Pierce, Mark C.

    2014-08-01

    A compact handpiece combining high resolution fluorescence (HRF) imaging with optical coherence tomography (OCT) was developed to provide real-time assessment of oral lesions. This multimodal imaging device simultaneously captures coregistered en face images with subcellular detail alongside cross-sectional images of tissue microstructure. The HRF imaging acquires a 712×594 μm2 field-of-view at the sample with a spatial resolution of 3.5 μm. The OCT images were acquired to a depth of 1.5 mm with axial and lateral resolutions of 9.3 and 8.0 μm, respectively. HRF and OCT images are simultaneously displayed at 25 fps. The handheld device was used to image a healthy volunteer, demonstrating the potential for in vivo assessment of the epithelial surface for dysplastic and neoplastic changes at the cellular level, while simultaneously evaluating submucosal involvement. We anticipate potential applications in real-time assessment of oral lesions for improved surveillance and surgical guidance.

  2. Design and characterization of a handheld multimodal imaging device for the assessment of oral epithelial lesions

    PubMed Central

    Higgins, Laura M.; Pierce, Mark C.

    2014-01-01

    Abstract. A compact handpiece combining high resolution fluorescence (HRF) imaging with optical coherence tomography (OCT) was developed to provide real-time assessment of oral lesions. This multimodal imaging device simultaneously captures coregistered en face images with subcellular detail alongside cross-sectional images of tissue microstructure. The HRF imaging acquires a 712×594  μm2 field-of-view at the sample with a spatial resolution of 3.5  μm. The OCT images were acquired to a depth of 1.5 mm with axial and lateral resolutions of 9.3 and 8.0  μm, respectively. HRF and OCT images are simultaneously displayed at 25 fps. The handheld device was used to image a healthy volunteer, demonstrating the potential for in vivo assessment of the epithelial surface for dysplastic and neoplastic changes at the cellular level, while simultaneously evaluating submucosal involvement. We anticipate potential applications in real-time assessment of oral lesions for improved surveillance and surgical guidance. PMID:25104410

  3. Physiological assessment of coronary lesion severity: fractional flow reserve versus nonhyperaemic indices.

    PubMed

    Robertson, Keith E; Hennigan, Barry; Berry, Colin; Oldroyd, Keith G

    2015-08-01

    Coronary angiography alone cannot accurately identify the haemodynamic impact of a coronary artery stenosis. Current international guidelines for myocardial revascularization recommend that inducible ischaemia should be demonstrated before the consideration of percutaneous coronary intervention. Invasive physiological assessment of coronary stenosis severity has increasingly been utilized for this purpose and use of the best validated technique, fractional flow reserve (FFR), has been shown to improve clinical outcomes in patients with stable and unstable coronary artery disease. This has led to the use of FFR being recommended in international revascularization guidelines, despite which, clinical uptake has been limited. One potential reason for slow adoption has been the requirement for maximal hyperaemia at the time of FFR measurement, usually achieved by the administration of pharmacological vasodilators such as adenosine. In some healthcare systems, adenosine is expensive and, in addition, its use can be associated with significant, albeit transient, adverse effects that patients (and some operators) find uncomfortable. Consequently, several methods of nonhyperaemic lesion assessment and their potential role in decision making have been reported. In this review we will review and discuss the current evidence for hyperaemic and nonhyperaemic methods of lesion assessment. We will also look at hybrid strategies that utilize both hyperaemic and nonhyperaemic methods as a means of potentially maintaining diagnostic accuracy while minimizing the requirement for adenosine administration and discuss whether or not they represent viable clinical alternatives.

  4. Collateral Ventilation to Congenital Hyperlucent Lung Lesions Assessed on Xenon-Enhanced Dynamic Dual-Energy CT: an Initial Experience

    PubMed Central

    Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

    2011-01-01

    Objective We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Materials and Methods Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Results Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Conclusion Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung. PMID:21228937

  5. [Forensic medical assessment of the mechanisms of development of gunshot lesions caused by elastic destructive agents].

    PubMed

    Musin, É Kh; Roman'ko, N A; Makarov, I Iu; Kutsenko, K I

    2012-01-01

    This paper reports the results of analysis of the data obtained in experimental studies and practical expert assessments of body injuries inflicted by rubber balls for traumatic weapons. The causes accounting for the polymorphism of such injuries and the mechanisms of their development were elucidated by means of damage simulation taking into consideration the physical and dynamic properties of elastic ball-type destructive agents and the morphological structure of different anatomical regions of the human body. The results of the study may be of interest for differential diagnostics of gunshot lesions caused by elastic destructive agents.

  6. Increasing extracellular potassium results in subthalamic neuron activity resembling that seen in a 6-hydroxydopamine lesion.

    PubMed

    Strauss, Ulf; Zhou, Fu-Wen; Henning, Jeannette; Battefeld, Arne; Wree, Andreas; Köhling, Rüdiger; Haas, Stefan Jean-Pierre; Benecke, Reiner; Rolfs, Arndt; Gimsa, Ulrike

    2008-06-01

    Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). Although altered extracellular potassium concentration ([K+]o) and sensitivity to [K+]o modulates neuronal activity, little is known about the potassium balance in the healthy and diseased STN. In vivo measurements of [K+]o using ion-selective electrodes demonstrated a twofold increase in the decay time constant of lesion-induced [K+]o transients in the STN of adult Wistar rats with a unilateral 6-hydroxydopamine (6-OHDA) median forebrain bundle lesion, employed as a model of PD, compared with nonlesioned rats. Various [K+]o concentrations (1.5-12.5 mM) were applied to in vitro slice preparations of three experimental groups of STN slices from nonlesioned control rats, ipsilateral hemispheres, and contralateral hemispheres of lesioned rats. The majority of STN neurons of nonlesioned rats and in slices contralateral to the lesion fired spontaneously, predominantly in a regular pattern, whereas those in slices ipsilateral to the lesion fired more irregularly or even in bursts. Experimentally increased [K+]o led to an increase in the number of spontaneously firing neurons and action potential firing rates in all groups. This was accompanied by a decrease in the amplitude of post spike afterhyperpolarization (AHP) and the amplitude and duration of the posttrain AHP. Lesion effects in ipsilateral neurons at physiological [K+]o resembled the effects of elevated [K+]o in nonlesioned rats. Our data suggest that changed potassium sensitivity due to conductivity alterations and delayed clearance may be critical for shaping STN activity in parkinsonian states.

  7. Athena: Assessment Phase Activities

    NASA Astrophysics Data System (ADS)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  8. Lesion-specific DNA-binding and repair activities of human O6-alkylguanine DNA alkyltransferase

    PubMed Central

    Melikishvili, Manana; Fried, Michael G.

    2012-01-01

    Binding experiments with alkyl-transfer-active and -inactive mutants of human O6-alkylguanine DNA alkyltransferase (AGT) show that it forms an O6-methylguanine (6mG)-specific complex on duplex DNA that is distinct from non-specific assemblies previously studied. Specific complexes with duplex DNA have a 2:1 stoichiometry that is formed without accumulation of a 1:1 intermediate. This establishes a role for cooperative interactions in lesion binding. Similar specific complexes could not be detected with single-stranded DNA. The small difference between specific and non-specific binding affinities strongly limits the roles that specific binding can play in the lesion search process. Alkyl-transfer kinetics with a single-stranded substrate indicate that two or more AGT monomers participate in the rate-limiting step, showing for the first time a functional link between cooperative binding and the repair reaction. Alkyl-transfer kinetics with a duplex substrate suggest that two pathways contribute to the formation of the specific 6mG-complex; one at least first order in AGT, we interpret as direct lesion binding. The second, independent of [AGT], is likely to include AGT transfer from distal sites to the lesion in a relatively slow unimolecular step. We propose that transfer between distal and lesion sites is a critical step in the repair process. PMID:22810209

  9. The association between sterilizing activity and drug distribution into tuberculosis lesions

    PubMed Central

    Prideaux, Brendan; Via, Laura E.; Zimmerman, Matthew D.; Eum, Seokyong; Sarathy, Jansy; O’Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M.; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, TaeSun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N.; Barry, Clifton E.; Dartois, Véronique

    2015-01-01

    Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a MALDI mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside1. In contrast, moxifloxacin which is active in vitro against persisters, a sub-population of Mycobacterium tuberculosis that persists in specific niches under drug pressure, and achieved treatment shortening in mice2, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We also suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration contributes to treatment outcome has wide implications for TB. PMID:26343800

  10. Computerized self-assessment of automated lesion segmentation in breast ultrasound: implication for CADx applied to findings in the axilla

    NASA Astrophysics Data System (ADS)

    Drukker, K.; Giger, M. L.

    2008-03-01

    We developed a self-assessment method in which the CADx system provided a confidence level for its lesion segmentations. The self-assessment was performed by a fuzzy-inference system based on 4 computer-extracted features of the computer-segmented lesions in a leave-one-case-out evaluation protocol. In instances where the initial segmentation received a low assessment rating, lesions were re-segmented using the same segmentation method but based on a user-defined region-of-interest. A total of 542 cases with 1133 lesions were collected in this study, and we focused here on the 97 normal lymph nodes in this dataset since these pose challenges for automated segmentation due to their inhomogeneous appearance. The percentage of all lesions with satisfactory segmentation (i.e., normalized overlap with the radiologist-delineated lesion >=0.3) was 85%. For normal lymph nodes, however, this percentage was only 36%. Of the lymph nodes, 53 received a low confidence rating (<0.3) for their initial segmentation. When those lymph nodes were re-segmented, the percentage with a satisfactory segmentation improved to 80.0%. Computerassessed confidence levels demonstrated potential to 1) help radiologists decide whether to use or disregard CADx output, and 2) provide a guide for improvement of lesion segmentation.

  11. Application of high resolution pQCT analysis for the assessment of a bone lesion: a technical note.

    PubMed

    Rubinacci, A; Tresoldi, D; Villa, I; Rizzo, G; Gaudio, D; De Angelis, D; Gibelli, D; Cattaneo, C

    2015-01-01

    Peripheral quantitative computed tomography (pQCT) has found new fields of application in bone medicine, but none of them concerns the forensic practice. This study exposes the potential of pQCT applied to a penetrating lesion in a vertebral body. A pQCT scanner was used for the measurements (XCT Research SA+; Stratec Medizintechnik GmbH, Pforzheim, Germany). A more precise reconstruction of the path of the lesion within the trabecular bone was reached, with more details concerning the morphological characteristics of the lesion inside the vertebral body, and the elaboration of a 3D model was created, which allowed the operator to define the volume of the lack of tissues related to the lesion. The application of pQCT scan proved to be a potentially useful tool for the assessment of bone lesions, although further studies are needed in order to verify its applicability to forensic context.

  12. Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats.

    PubMed

    Ortiz-Pulido, R; Hernández-Briones, Z S; Tamariz-Rodríguez, A; Hernández, M E; Aranda-Abreu, G E; Coria-Avila, G A; Manzo, J; García, L I

    2017-06-01

    Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice

    PubMed Central

    Herold, Marco J.

    2016-01-01

    Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53−/− mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers. PMID:27621418

  14. Complement is activated in progressive multiple sclerosis cortical grey matter lesions.

    PubMed

    Watkins, Lewis M; Neal, James W; Loveless, Sam; Michailidou, Iliana; Ramaglia, Valeria; Rees, Mark I; Reynolds, Richard; Robertson, Neil P; Morgan, B Paul; Howell, Owain W

    2016-06-22

    The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression. We analysed complement expression and activation by immunocytochemistry and in situ hybridisation in frozen or formalin-fixed paraffin-embedded post-mortem tissue blocks from 22 progressive MS cases and made comparisons to inflammatory central nervous system disease and non-neurological disease controls. Expression of the transcript for C1qA was noted in neurons and the activation fragment and opsonin C3b-labelled neurons and glia in the MS cortical and deep grey matter. The density of immunostained cells positive for the classical complement pathway protein C1q and the alternative complement pathway activation fragment Bb was significantly increased in cortical grey matter lesions in comparison to control grey matter. The number of cells immunostained for the membrane attack complex was elevated in cortical lesions, indicating complement activation to completion. The numbers of classical (C1-inhibitor) and alternative (factor H) pathway regulator-positive cells were unchanged between MS and controls, whilst complement anaphylatoxin receptor-bearing microglia in the MS cortex were found closely apposed to cortical neurons. Complement immunopositive neurons displayed an altered nuclear morphology, indicative of cell stress/damage, supporting our finding of significant neurodegeneration in cortical grey matter lesions. Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the

  15. Impairment only on the fluency subtest of the Frontal Assessment Battery after prefrontal lesions.

    PubMed

    Chapados, Catherine; Petrides, Michael

    2013-10-01

    The Frontal Assessment Battery is a set of six subtests that is used widely to assess frontal cortical executive dysfunction. Performance on the Frontal Assessment Battery has been shown to be sensitive to various neurodegenerative diseases, but it has never been shown to be sensitive to damage restricted to the frontal cortex. Thus, despite its wide use, it has never been validated on an appropriate population of patients with frontal lesions. The present study shows that, of the six subtests that comprise the Frontal Assessment Battery, only performance on the verbal fluency subtest (mental flexibility) was specifically sensitive to injury restricted to the frontal cortex. Performance of patients with damage to the dorsal part of the medial frontal region in the language-dominant left hemisphere was impaired. None of these patients was aphasic at the time of testing. The critical region in the dorsomedial frontal cortex includes the supplementary speech zone but is not restricted to it: it extends into the cingulate motor region and the paracingulate cortex as well as the medial prefrontal areas 8 and 9. The results indicate that the Frontal Assessment Battery is not a sensitive measure of prefrontal cortical dysfunction, except for the verbal fluency subtest.

  16. Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes.

    PubMed

    Kasasbeh, Aimen S; Christensen, Søren; Straka, Matus; Mishra, Nishant; Mlynash, Michael; Bammer, Roland; Albers, Gregory W; Lansberg, Maarten G

    2016-12-01

    The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature. We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time. We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T0 plus 1.6 times the width of the venous output function (P<0.001; R(2)=0.49). This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended. © 2016 American Heart Association, Inc.

  17. Efficacy of sealing proximal early active lesions: an 18-month clinical study evaluated by conventional and subtraction radiography.

    PubMed

    Martignon, S; Ekstrand, K R; Ellwood, R

    2006-01-01

    This study assessed the efficacy of sealing proximal lesions on adult patients using a split-mouth design. Eighty-two 15- to 39-year-olds from the Dental Faculties in Copenhagen and Bogotá participated, each having 2 or more proximal lesions in the following radiographic stages: (1) lesion restricted to the outer half of enamel; (2) lesion from the inner half of enamel including the enamel dentine junction, and (3) lesion restricted to the outer third of dentine. Standardized geometrically aligned baseline and follow-up radiographs were obtained. One randomly selected lesion (test) in each patient was sealed with 1 of 2 resins. The patients were instructed to floss all the proximal lesions 3 times per week. The baseline to 18 months difference in caries lesion progression status was assessed using 3 methods: (1) radiographs were independently assessed visually; (2) radiographs were read in pairs, and (3) using subtraction radiography of digitized images. A total of 72 subjects finished the study (12.2% dropout). The compliance concerning flossing was poor (15%). For the repeated examinations kappa was 0.84 for the visual examination, 0.44 for the paired readings and 0.84 for the subtraction examination. Two test lesions and 1 control lesion were restored. For the independent radiograph assessment method 10 and 26% progressed in the test and control group, respectively (p > 0.05); with the paired radiograph method the corresponding data were 22% in the test and 47% in the control groups (p < 0.01). By subtraction radiography 44% of the test group and 84% of the control were judged to have progressed (p < 0.001). The sealing technique was superior to instructing patients to floss, and subtraction radiography appeared to be the most sensitive method for assessing lesion progression. Copyright 2006 S. Karger AG, Basel.

  18. Assessment of natural enamel lesions with optical coherence tomography in comparison with microfocus x-ray computed tomography

    PubMed Central

    Espigares, Jorge; Sadr, Alireza; Hamba, Hidenori; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Sumi, Yasunori

    2015-01-01

    Abstract. A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x-ray computed tomography (μCT) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by μCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In μCT, the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer–Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to 606  μm in SS-OCT. A correlation between μCT and SS-OCT was found regarding lesion depth (R=0.81, p<0.001) and also surface layer thickness (R=0.76, p<0.005). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high-resolution μCT without the use of x-ray. PMID:26158079

  19. Assessment of natural enamel lesions with optical coherence tomography in comparison with microfocus x-ray computed tomography.

    PubMed

    Espigares, Jorge; Sadr, Alireza; Hamba, Hidenori; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Sumi, Yasunori

    2015-01-01

    A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x-ray computed tomography ([Formula: see text]) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by μCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In [Formula: see text], the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer-Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to [Formula: see text] in SS-OCT. A correlation between [Formula: see text] and SS-OCT was found regarding lesion depth ([Formula: see text], [Formula: see text]) and also surface layer thickness ([Formula: see text], [Formula: see text]). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high-resolution [Formula: see text] without the use of x-ray.

  20. Simultaneous assessment of pulsating and total blood in inflammatory skin lesions using functional diffuse reflectance spectroscopy in the visible range.

    PubMed

    Seo, InSeok; Bargo, Paulo R; Kollias, Nikiforos

    2010-01-01

    We present a simple and cost-effective optical technique for the simultaneous assessment of pulsating and total blood noninvasively in an inflammatory skin lesion. Acquisitions of diffuse reflectance spectra in the visible range at 6 Hz are used to trace the oscillating components of reflectance. Measurements on erythematous lesions from a UV insult show slow changing signal at about 0.1 Hz and heart-driven regular oscillations at about 1 Hz simultaneously. The results demonstrate the potential of the technique in monitoring both pulsating and steady components of the blood in inflammatory lesions of the skin.

  1. ROC study of the effect of stereoscopic imaging on assessment of breast lesions.

    PubMed

    Chan, Heang-Ping; Goodsitt, Mitchell M; Helvie, Mark A; Hadjiiski, Lubomir M; Lydick, Justin T; Roubidoux, Marilyn A; Bailey, Janet E; Nees, Alexis; Blane, Caroline E; Sahiner, Berkman

    2005-04-01

    An observer performance study was conducted to evaluate the usefulness of assessing breast lesion characteristics with stereomammography. Stereoscopic image pairs of 158 breast biopsy tissue specimens were acquired with a GE Senographe 2000D full field digital mammography system using a 1.8x magnification geometry. A phantom-shift method equivalent to a stereo shift angle of +/- 3 degrees relative to a central axis perpendicular to the detector was used. For each specimen, two pairs of stereo images were taken at approximately orthogonal orientations. The specimens contained either a mass, microcalcifications, both, or normal tissue. Based on pathological analysis, 39.9% of the specimens were found to contain malignancy. The digital specimen radiographs were displayed on a high resolution MegaScan CRT monitor driven by a DOME stereo display board using in-house developed software. Five MQSA radiologists participated as observers. Each observer read the 316 specimen stereo image pairs in a randomized order. For each case, the observer first read the monoscopic image and entered his/her confidence ratings on the presence of microcalcifications and/or masses, margin status, BI-RADS assessment, and the likelihood of malignancy. The corresponding stereoscopic images were then displayed on the same monitor and were viewed through stereoscopic LCD glasses. The observer was free to change the ratings in every category after stereoscopic reading. The ratings of the observers were analyzed by ROC methodology. For the 5 MQSA radiologists, the average Az value for estimation of the likelihood of malignancy of the lesions improved from 0.70 for monoscopic reading to 0.72 (p=0.04) after stereoscopic reading, and the average Az value for the presence of microcalcifications improved from 0.95 to 0.96 (p=0.02). The Az value for the presence of masses improved from 0.80 to 0.82 after stereoscopic reading, but the difference fell short of statistical significance (p=0.08). The visual

  2. Assessment of chemomechanical removal of carious lesions using Papacarie Duo™: randomized longitudinal clinical trial.

    PubMed

    Matsumoto, Simone Ferreira Borges; Motta, Lara Jansiski; Alfaya, Thays Almeida; Guedes, Carolina Cardoso; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalil

    2013-01-01

    Chemomechanical removal of carious lesions consists of the dissolution of carious tissue by the application of a natural or synthetic agent, followed by atraumatic mechanical removal. The aim of the present study was to assess the effectiveness of Papacarie Duo ® gel in the chemomechanical removal of carious lesions in primary teeth in comparison to the traditional method (low-speed bur). A randomized clinical trial was conducted with 20 children between 5 and 8 years of age. Two teeth were treated in each child (split-mouth design), with the randomization of two methods: Group 1 - chemomechanical caries removal with Papacarie Duo™; and Group 2 - removal of carious dentin tissue using a low-speed bur. Both methods involved restoration with glass ionomer cement and follow up. The following aspects were evaluated: time required for the procedure; pain (face evaluation scale); retention of the restorative material in the cavity; and the presence of secondary caries after 30 days. Chi-squared test, Student's t-test, and Wilcoxon test. No statistically significant differences between methods were found regarding time required for the procedure (P = 0.13), the occurrence of pain (P = 0.585), or restoration status at the 30-day clinical evaluation (P = 0.713). The findings of the present study demonstrate that the two methods achieve similar results. The advantages of minimally invasive treatment, such as chemomechanical caries removal with Papacarie Duo™, are its ease of use, patient comfort, and the fact that it causes less damage to dental tissue.

  3. Quantitative assessment of the age of fibrotic lesions using polarized light microscopy and digital image analysis.

    PubMed

    Pickering, J G; Boughner, D R

    1991-05-01

    Reliable histologic methods for gauging the maturity of fibrotic lesions are limited, making interventions in the healing process difficult to assess. As collagen ages there is enhanced birefringence due to increased molecular and fibrillar organization. The purpose of this study was to develop a microscopal technique to quantify this process and to determine its ability to distinguish scars of varying ages. Fibrosis in the rat gracilis muscle was studied 5 to 63 days after superficial injury. Sections were stained with picrosirius red and illuminated with monochromatic, polarized light. The microscope fields were digitized using a computer-video system yielding an image in which noncollagenous material was dark (gray level 0) and collagen was depicted by grey levels 1 to 255. In the fibrosis model used, the collagen area fraction plateaued at 80% by day 21. The median collagen grey level increased progressively as the scar aged. It is concluded that this histologic, nondestructive technique can reliably quantify age-related optical properties of fibrotic collagen and that this could be used to determine the maturity of fibrotic lesions.

  4. Influence of toxoplasmosis on acetylcholinesterase activity, nitric oxide levels and cellular lesion on the brain of mice.

    PubMed

    Tonin, Alexandre A; Da Silva, Aleksandro S; Thomé, Gustavo R; Sangoi, Manuela B; Oliveira, Lizielle S; Flores, Mariana M; Schetinger, Maria Rosa C; Fighera, Rafael A; Moresco, Rafael N; Camillo, Giovana; Vogel, Fernanda S F; Lopes, Sonia T A

    2014-08-01

    The objective of this study was to investigate the activity of acetylcholinesterase (AChE), nitrite/nitrate (NOx) levels, as well as the biomarkers of cellular damage in the brain of mice experimentally infected with Toxoplasma gondii. Sixty mice were divided into two experiments: in experiment I the mice were infected with T. gondii/RH strain, while in experiment II they were infected with T. gondii, strains VEG and ME-49. Our evaluations were carried out on brain homogenized samples, assessing the AChE and glutathione reductase (GR) activities, and NOx, TBARS and AOPP levels in all the infected animals, compared with the control group. In both experiments, I and II, it was observed an increase in the activity of AChE and GR, as well as in the levels of NOx in the brain of infected mice with T. gondii. TBARS levels were increased in mice infected with the three different strains, RH, ME-49, and VEG. AOPP concentration was increased only in mice infected with the RH strain. Animals infected with the strains VEG and ME-49 showed histological lesions, associated with the presence of the parasite in the brain. Therefore, the infection by T. gondii is able to interfere in cholinesterase activity and NO levels, in association with oxidative stress and histological lesion. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. NI-79RAPID ASSESSMENT OF LESION VOLUMES FOR PATIENTS WITH GLIOMA USING THE SMARTBRUSH SOFTWARE PACKAGE

    PubMed Central

    Vaziri, Sana; Lafontaine, Marisa; Olson, Beck; Crane, Jason C.; Chang, Susan; Lupo, Janine; Nelson, Sarah J.

    2014-01-01

    The increasing interest in enhancing the RANO criteria by using quantitative assessments of changes in lesion size and image intensities has highlighted the need for rapid, easy-to-use tools that provide DICOM compatible outputs for evaluation of patients with glioma. To evaluate the performance of the SmartBrush software (Brainlab AG), which provides computer-assisted definitions of regions of interest (ROIs), a cohort of 20 patients with glioma (equal number having high and low grade and treated and un-treated) were scanned using a 3T whole-body MR system prior to surgical resection. The T2-weighted FLAIR, pre- and post-contrast T1-weighted gradient echo DICOM images were pushed from the scanner to an offline workstation where analysis of lesion volumes was performed using SmartBrush. Volumes of the T2Ls ranged from 7.9 to 110.2cm3 and the volumes of the CELs was 0.1 to 28.5 cm3 with 19/20 of the subjects having CELs and all 20 having T2Ls. the computer-assisted analysis was performed rapidly and efficiently, with the mean time for defining both lesions per subject was 5.77 (range 3.5 to 7.5) minutes. Prior analysis of ROIS with the SLICER package (www.slicer.org) took approximately 30 minutes/subject. SmartBrush provides lesion volumes and cross-sectional diameter as a PDF report, which can be stored in DICOM. The ROIs were also saved as DICOM objects and transferred to other packages for performing histogram analysis from ADC or other functional parameter maps. Ongoing studies that will be reported in this presentation are performing a similar analysis with multiple users in order to compare the relative intra- and inter-operator variations in terms of both the speed of analysis and the ROIs that are identified. Acknowledgements: The authors would like to acknowledge Rowena Thomson and Natalie Wright from Brainlab for helping to set up this study.

  6. GLENOHUMERAL MUSCLE ACTIVATION DURING PROVOCATIVE TESTS DESIGNED TO DIAGNOSE SUPERIOR LABRUM ANTERIOR-POSTERIOR LESIONS

    PubMed Central

    Wood, Vanessa J.C.; Sabick, Michelle B.; Pfeiffer, Ron P.; Kuhlman, Seth M.; Christensen, Jason H.; Curtin, Michael J.

    2012-01-01

    Background Despite considerable medical advances, arthroscopy remains the only definitive means of Superior Labrum Anterior-Posterior (SLAP) lesion diagnosis. Natural shoulder anatomic variants limit the reliability of radiographic findings and clinical evaluations are not consistent. Accurate clinical diagnostic techniques would be advantageous due to the invasiveness, patient risk, and financial cost associated with arthroscopy. Purpose The purpose was to examine the behavior of the joint stabilizing muscles in provocative tests for SLAP lesions. Electromyography was used to characterize the muscle behavior, with particular interest in the long head biceps brachii (LHBB), as activation of the long head and subsequent tension in the biceps tendon should, based on related research, elicit labral symptoms in SLAP lesion patients. Study Design Controlled Laboratory Study Methods Volunteers (N=21) without a history of shoulder pathology were recruited. The tests analyzed were Active Compression, Speed's, Pronated Load, Biceps I, Biceps II, Resisted Supination External Rotation, and Yergason's. Tests were performed with a dynamometer to improve reproducibility. Muscle activity was recorded for the long and short heads of the biceps brachii, anterior deltoid, pectoralis major, latissimus dorsi, infraspinatus, and supraspinatus. Muscle behavior for each test was characterized by peak activation and proportion of muscle activity. Results Speed's, Active Compression Palm-Up, Bicep I and Bicep II, produced higher long head activations. Resisted Supination External Rotation, Bicep I, Bicep II, and Yergason's, produced a higher LHBB proportion. Conclusion Bicep I, and Bicep II elicited promising long head behavior (high activation and selectivity). Speed's and Active Compression Palm-Up elicited higher activation of the LHBB , and Resisted Supination and Yergason's elicited selective LHBB activity. These top performing tests utilize a unique range of test variables that may

  7. Antifungal Activity of Plant Extracts against Candida Species from Oral Lesions

    PubMed Central

    Prabhakar, K.; Kumar, L. Sathish; Rajendran, S.; Chandrasekaran, M.; Bhaskar, K.; Sajit Khan, A. K.

    2008-01-01

    Seventy five patients with oral lesions attending the different departments of Rajah Muthiah Medical College and Hospital, Annamalai University were screened for Candida. Forty six (61.3%) Candida strains were isolated from the oral lesions. Of the 46 Candida strains, Candida albicans accounted for 35 (76.08%), Candida glabrata for 5 (10.86%), Candida tropicalis and Candida krusei for 2 (4.34%) each and Candida parapsilosis and Candida guilliermondii for one (2.17%) each. Antifungal activity of ethanol extracts of five plant species that included Syzygium jambolanum, Cassia siamea, Odina wodier, Momordica charantia and Melia azedarach and two algal species, Sargassum wightii and Caulerpa scalpelliformis were tested against 25 isolated strains by disc diffusion method. Antifungal activity was observed at 100 mg/ml for Syzygium jambolanum, Cassia siamea and Caulerpa scalpelliformis and at 10 mg/ml for Sargassum wightii. PMID:21369447

  8. Antifungal Activity of Plant Extracts against Candida Species from Oral Lesions.

    PubMed

    Prabhakar, K; Kumar, L Sathish; Rajendran, S; Chandrasekaran, M; Bhaskar, K; Sajit Khan, A K

    2008-11-01

    Seventy five patients with oral lesions attending the different departments of Rajah Muthiah Medical College and Hospital, Annamalai University were screened for Candida. Forty six (61.3%) Candida strains were isolated from the oral lesions. Of the 46 Candida strains, Candida albicans accounted for 35 (76.08%), Candida glabrata for 5 (10.86%), Candida tropicalis and Candida krusei for 2 (4.34%) each and Candida parapsilosis and Candida guilliermondii for one (2.17%) each. Antifungal activity of ethanol extracts of five plant species that included Syzygium jambolanum, Cassia siamea, Odina wodier, Momordica charantia and Melia azedarach and two algal species, Sargassum wightii and Caulerpa scalpelliformis were tested against 25 isolated strains by disc diffusion method. Antifungal activity was observed at 100 mg/ml for Syzygium jambolanum, Cassia siamea and Caulerpa scalpelliformis and at 10 mg/ml for Sargassum wightii.

  9. Reusable ultrasonic tissue mimicking hydrogels containing nonionic surface-active agents for visualizing thermal lesions.

    PubMed

    Park, Seong Keun; Guntur, S R Anjaneya Reddy; Lee, Kang Il; Paeng, Dong-Guk; Choi, Min Joo

    2010-01-01

    The present study aims to identify a new recipe for reusable tissue mimicking phantoms that allows the optical visualization of thermal lesions produced in various applications of therapeutic ultrasound where thermal mechanisms are important. The phantom was made of polyacrylamide hydrogel containing a nonionic surface-active agent (NiSAA) as a temperature-sensitive indicator. Threshold temperature above which a thermal lesion is regarded to be formed in the phantom is controlled by selecting an NiSAA. In the present study, three NiSAAs of polyoxyethylene alkyl ether series with nominal clouding points of 66 ( degrees )C, 70 ( degrees )C, and 80 ( degrees ) C were chosen. Test phantoms were prepared with polyacrylamide hydrogel, corn syrup and NiSAAs [5% (w/v)]. Key acoustic properties of the three NiSAA hydrogels were found to be similar to those of human liver. The phantoms were optically transparent at room temperature (25 ( degrees ) C) and became opaque after exceeding the clouding points. The transparency was recovered on cooling, although the system demonstrated hysteresis. The phantoms were tested both in their ability to provide visualization of thermal lesions produced by high-intensity focused ultrasound and also to examine any characteristic differences in the shape of the lesions formed at different threshold temperatures. The present study suggests that the NiSAA polyacrylamide hydrogel will be of a practical use in quality assurance in various applications of therapeutic ultrasound where thermal mechanisms are important.

  10. Polymer fraction of Aloe vera exhibits a protective activity on ethanol-induced gastric lesions.

    PubMed

    Park, Chul-Hong; Nam, Dong-Yoon; Son, Hyeong-U; Lee, Si-Rim; Lee, Hyun-Jin; Heo, Jin-Chul; Cha, Tae-Yang; Baek, Jin-Hong; Lee, Sang-Han

    2011-04-01

    For centuries, Aloe has been used as a herbal plant remedy against skin disorders, diabetes, and for its cardiac stimulatory activity. Here, we examined the gastroprotective effects of an Aloe vera polymer fraction (Avpf; molecular weight cut-off ≥50 kDa; 150 mg/kg body weight, p.o.) on an ethanol-induced gastric lesion mouse model. Mice pre-treated with Avpf had significantly fewer gastric lesions than their respective controls. To further examine the potential mechanism underlying this effect, we used reverse transcription-polymerase chain reaction to examine nitric oxide synthase and matrix metalloproteinase (MMP)mRNA expression on tissues from gastric lesions. Our results revealed that the mRNA expressions of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) were each reduced by ~50% in Avpf-treated mice vs. the controls, whereas, the mRNA expression levels of endothelial nitric oxide synthase remained unchanged. MMP-9, an index for gastric lesions, also alleviated the ethanol-treated gastric ulceration during Avpf treatment. These findings collectively suggest that Avpf significantly protects the gastric mucosa against ethanol-induced gastric damage, at least in part, by decreasing mRNA expression levels of not only iNOS and nNOS, but also MMP-9.

  11. The effect of retrosplenial cortex lesions in rats on incidental and active spatial learning.

    PubMed

    Nelson, A J D; Hindley, E L; Pearce, J M; Vann, S D; Aggleton, J P

    2015-01-01

    The study examined the importance of the retrosplenial cortex for the incidental learning of the spatial arrangement of distinctive features within a scene. In a modified Morris water-maze, rats spontaneously learnt the location of an escape platform prior to swimming to that location. For this, rats were repeatedly placed on a submerged platform in one corner of either a rectangular (Experiment 1) or square (Experiments 2, 3) pool with walls of different appearance. The rats were then released in the center of the pool for their first test trial. In Experiment 1, the correct corner and its diagonally opposite partner (also correct) were specified by the geometric properties of the pool. Rats with retrosplenial lesions took longer to first reach a correct corner, subsequently showing an attenuated preference for the correct corners. A reduced preference for the correct corner was also found in Experiment 2, when platform location was determined by the juxtaposition of highly salient visual cues (black vs. white walls). In Experiment 3, less salient visual cues (striped vs. white walls) led to a robust lesion impairment, as the retrosplenial lesioned rats showed no preference for the correct corner. When subsequently trained actively to swim to the correct corner over successive trials, retrosplenial lesions spared performance on all three discriminations. The findings not only reveal the importance of the retrosplenial cortex for processing various classes of visuospatial information but also highlight a broader role in the incidental learning of the features of a spatial array, consistent with the translation of scene information.

  12. Functional assessment of lesion severity without using the pressure wire: coronary imaging and blood flow simulation.

    PubMed

    Papafaklis, Michail I; Mavrogiannis, Michail C; Siogkas, Panagiotis K; Lakkas, Lampros S; Katsouras, Christos S; Fotiadis, Dimitrios I; Michalis, Lampros K

    2017-09-19

    Hemodynamic indices derived from measurements with the pressure wire (primarily fractional flow reserve [FFR]) have been established as a reliable tool for assessing coronary stenoses and improving clinical decision making. However, the use of the pressure wire constitutes a hurdle for the universal adoption of physiology-guided patient management. Technological advancements have enabled the large-scale application of blood flow simulation (computational fluid dynamics [CFD]) to medical imaging, thereby enabling the virtual assessment of coronary physiology. Areas covered: This review summarizes the stand-alone non-invasive (coronary computed tomographic imaging) and invasive (coronary angiography) imaging approaches which were initially used for predicting FFR, and focuses on the use of blood flow modeling for functional assessment of coronary lesions in clinical practice. Expert commentary: Validation studies of CFD-derived methodologies for functional assessment have shown that virtual indices correlate well and have good diagnostic accuracy compared to pressure wire-FFR despite inherent limitations of spatial resolution and assumptions regarding boundary conditions in flow modeling. Beyond point-to-point agreement with FFR, further studies are needed to demonstrate the clinical safety/efficacy of these computational tools regarding patient outcomes. Such evidence base could support the incorporation of these methodologies into routine patient management for decision making and reliable risk stratification.

  13. Activity assessment of eosinophilic esophagitis.

    PubMed

    Schoepfer, Alain; Safroneeva, Ekaterina

    2014-01-01

    The activity of eosinophilic esophagitis (EoE) can be assessed with patient-reported outcomes and biologic measures. Patient-reported outcomes include symptoms and quality of life, whereas biologic measures refer to endoscopic, histologic, and biochemical activity (e.g. blood biomarkers). So far, a validated tool to assess EoE activity in the above-mentioned dimensions is lacking. Given the lack of a standardized way to assess EoE activity in the various dimensions, the results of different clinical trials may be difficult to compare. For symptom assessment in adult patients, the symptom 'dysphagia' should be evaluated according to different standardized food consistencies. Furthermore, symptom assessment should take into account the following items: avoidance of specific food categories, food modification, and time to eat a regular meal. A distinct symptom recall period (e.g. 2 weeks) has to be defined for symptom assessment. Performing an 'esophageal stress test' with ingestion of a standardized meal to measure symptom severity bears the potential risk of acute food bolus impaction and should therefore be avoided. The description of endoscopic findings in EoE has meanwhile been standardized. Histologic evaluation of EoE activity should report either the size of the high-power field used or count the eosinophils per mm(2). There is a current lack of blood biomarkers demonstrating a good correlation with histologic activity in esophageal biopsies. The development and validation of an adult and pediatric EoE activity index is urgently needed not only for clinical trials and observational studies, but also for daily practice.

  14. Assessment of performance and reproducibility of applying a content-based image retrieval scheme for classification of breast lesions.

    PubMed

    Gundreddy, Rohith Reddy; Tan, Maxine; Qiu, Yuchen; Cheng, Samuel; Liu, Hong; Zheng, Bin

    2015-07-01

    To develop a new computer-aided diagnosis (CAD) scheme using a content-based image retrieval (CBIR) approach for classification between the malignant and benign breast lesions depicted on the digital mammograms and assess CAD performance and reproducibility. An image dataset including 820 regions of interest (ROIs) was used. Among them, 431 ROIs depict malignant lesions and 389 depict benign lesions. After applying an image preprocessing process to define the lesion center, two image features were computed from each ROI. The first feature is an average pixel value of a mapped region generated using a watershed algorithm. The second feature is an average pixel value difference between a ROI's center region and the rest of the image. A two-step CBIR approach uses these two features sequentially to search for ten most similar reference ROIs for each queried ROI. A similarity based classification score was then computed to predict the likelihood of the queried ROI depicting a malignant lesion. To assess the reproducibility of the CAD scheme, we selected another independent testing dataset of 100 ROIs. For each ROI in the testing dataset, we added four randomly queried lesion center pixels and examined the variation of the classification scores. The area under the ROC curve (AUC) = 0.962 ± 0.006 was obtained when applying a leave-one-out validation method to 820 ROIs. Using the independent testing dataset, the initial AUC value was 0.832 ± 0.040, and using the median classification score of each ROI with five queried seeds, AUC value increased to 0.878 ± 0.035. The authors demonstrated that (1) a simple and efficient CBIR scheme using two lesion density distribution related features achieved high performance in classifying breast lesions without actual lesion segmentation and (2) similar to the conventional CAD schemes using global optimization approaches, improving reproducibility is also one of the challenges in developing CAD schemes using a CBIR based regional

  15. Proteasome activity is required for the initiation of precancerous pancreatic lesions

    PubMed Central

    Furuyama, Takaki; Tanaka, Shinji; Shimada, Shu; Akiyama, Yoshimitsu; Matsumura, Satoshi; Mitsunori, Yusuke; Aihara, Arihiro; Ban, Daisuke; Ochiai, Takanori; Kudo, Atsushi; Fukamachi, Hiroshi; Arii, Shigeki; Kawaguchi, Yoshiya; Tanabe, Minoru

    2016-01-01

    Proteasome activity is significantly increased in advanced cancers, but its role in cancer initiation is not clear, due to difficulties in monitoring this process in vivo. We established a line of transgenic mice that carried the ZsGreen-degronODC (Gdeg) proteasome reporter to monitor the proteasome activity. In combination with Pdx-1-Cre;LSL-KrasG12D model, proteasome activity was investigated in the initiation of precancerous pancreatic lesions (PanINs). Normal pancreatic acini in Gdeg mice had low proteasome activity. By contrast, proteasome activity was increased in the PanIN lesions that developed in Gdeg;Pdx-1-Cre;LSL-KrasG12D mice. Caerulein administration to Gdeg;Pdx-1-Cre;LSL-KrasG12D mice induced constitutive elevation of proteasome activity in pancreatic tissues and accelerated PanIN formation. The proteasome inhibitor markedly reduced PanIN formation in Gdeg;Pdx-1-Cre;LSL-KrasG12D mice (P = 0.001), whereas it had no effect on PanIN lesions that had already formed. These observations indicated the significance of proteasome activity in the initiation of PanIN but not the maintenance per se. In addition, the expressions of pERK and its downstream factors including cyclin D1, NF-κB, and Cox2 were decreased after proteasome inhibition in PanINs. Our studies showed activation of proteasome is required specifically for the initiation of PanIN. The roles of proteasome in the early stages of pancreatic carcinogenesis warrant further investigation. PMID:27244456

  16. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions.

    PubMed

    Kimberlin, David W; Baley, Jill

    2013-02-01

    Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother's previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.

  17. Intra-lesional stereo-EEG activity in Taylor 's focal cortical dysplasia.

    PubMed

    Francione, Stefano; Nobili, Lino; Cardinale, Francesco; Citterio, Alberto; Galli, Carlo; Tassi, Laura

    2003-09-01

    Focal cortical dysplasia are a frequent histological finding in epilepsy surgery series. Among the different types of focal cortical dysplasia, distinctive anatomical, electrical and clinical details have been identified for Taylor's focal cortical dysplasia, and in a recent article we reported a better post-surgical outcome in Taylor's focal cortical dysplasia than in other histological subtypes of cortical dysplasias. In the present study, we analysed the intra-lesional electrical activity directly recorded inside Taylor's focal cortical dysplasia during a stereo-EEG diagnostic procedure in 21 patients selected from among the 27 cases in which post-operative neuropathological examination demonstrated this kind of lesion. Our data show the existence of a peculiar interictal pattern characterised by the presence of repetitive and rhythmic spike and poly-spike and wave, frequently associated with short bursts of fusiform micro poly-spikes. Moreover, an almost pathognomonic ictal pattern (mid-amplitude 14-18 Hz rhythmic activity followed by a low voltage recruiting fast activity) is present in 12 of these 21 patients. These electrical peculiarities suggest a high level of epileptogenicity of Taylor's focal cortical dysplasia and could possibly explain the high percentage of post-surgical success among patients with this kind of lesion. Copyright John Libbey Eurotext 2003.

  18. Pemphigus vulgaris activity score and assessment of convergent validity.

    PubMed

    Chams-Davatchi, Cheyda; Rahbar, Ziba; Daneshpazhooh, Maryam; Mortazavizadeh, Seyed Mohammad Ali; Akhyani, Maryam; Esmaili, Nafiseh; Balighi, Kamran

    2013-05-07

    Pemphigus is a rare autoimmune blistering disease with different phenotypes. The evaluation of therapeutic interventions requires a reliable, valid and feasible to use measurement. However, there is no gold standard to measure the disease activity in clinical trials. In this study we aimed to introduce the pemphigus vulgaris activity score (PVAS) measurement and to assess the convergent validity with the experts' opinion of disease activity. In PVAS scoring, the distribution of pemphigus vulgaris antigen expression in different anatomical regions is taking in to account with special consideration of the healing process. PVAS is a 0-18 scale, based on the extent of mucocutaneous involvement, type of lesion and the presence of Nikolsky's sign. The sum of the scores of total number of lesions, number of different anatomic regions involvement and Nikolsky's sign is weighted by the type of lesion. In the present study, PVAS was assessed in 50 patients diagnosed with pemphigus vulgaris by one dermatologist. Independently, five blinded experts scored all the patients through physician's global assessment (PGA). The convergent validity with experts' opinion was assessed. The Spearman coefficient of correlation showed the acceptable value of 0.751 (95%CI: 0.534- 0.876). PVAS is a valid, objective and simple-to-use scoring measurement. It showed a good correlation with PGA of pemphigus disease activity in Iranian patients with pemphigus vulgaris.

  19. Computer-aided analysis with Image J for quantitatively assessing psoriatic lesion area.

    PubMed

    Sun, Z; Wang, Y; Ji, S; Wang, K; Zhao, Y

    2015-11-01

    Body surface area is important in determining the severity of psoriasis. However, objective, reliable, and practical method is still in need for this purpose. We performed a computer image analysis (CIA) of psoriatic area using the image J freeware to determine whether this method could be used for objective evaluation of psoriatic area. Fifteen psoriasis patients were randomized to be treated with adalimumab or placebo in a clinical trial. At each visit, the psoriasis area of each body site was estimated by two physicians (E-method), and standard photographs were taken. The psoriasis area in the pictures was assessed with CIA using semi-automatic threshold selection (T-method), or manual selection (M-method, gold standard). The results assessed by the three methods were analyzed with reliability and affecting factors evaluated. Both T- and E-method correlated strongly with M-method, and T-method had a slightly stronger correlation with M-method. Both T- and E-methods had a good consistency between the evaluators. All the three methods were able to detect the change in the psoriatic area after treatment, while the E-method tends to overestimate. The CIA with image J freeware is reliable and practicable in quantitatively assessing the lesional of psoriasis area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Bennett lesions in baseball players detected by magnetic resonance imaging: assessment of association factors.

    PubMed

    Park, Jin-Young; Noh, Young-Min; Chung, Seok-Won; Moon, Sung-Gyn; Ha, Dae-Ho; Lee, Ki-Sun; Chung, Seok Won

    2016-05-01

    The purpose of this study was to evaluate the characteristics of Bennett lesions in baseball players compared with those without a Bennett lesion and to identify other possible factors associated with Bennett lesions on magnetic resonance imaging (MRI). We investigated 388 male baseball players with a career >1 year. Demographic factors and a routine physical examination, including glenohumeral internal rotation difference, scapular dyskinesis, and various pathologic changes, were reviewed on MRI to identify relative factors for Bennett lesions. Of the 388 patients evaluated, 125 (32.2%) were diagnosed with Bennett lesions of the shoulder. No significant differences were observed between the groups in demographic factors, physical examination results, visual analog scale score, American Shoulder and Elbow Surgeons score, or prevalence of concomitant diseases. However, players with Bennett lesions had played baseball longer than those without the lesions (P < .001). An association was found between Bennett lesions and the length of time that a patient with a Bennett lesion had played baseball. The prevalence of pathologic lesions detected on MRI and the physical examination results were not different between players with and without Bennett lesions. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  1. Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

    PubMed

    Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

    2007-04-01

    There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

  2. Diagnostic accuracy of history taking and physical examination for assessing anterior cruciate ligament lesions of the knee in primary care.

    PubMed

    Wagemakers, Harry P; Luijsterburg, Pim A; Boks, Simone S; Heintjes, Edith M; Berger, Marjolein Y; Verhaar, Jan A; Koes, Bart W; Bierma-Zeinstra, Sita M

    2010-09-01

    To assess the diagnostic accuracy of history taking and physical examination for assessing anterior cruciate ligament (ACL) lesions in primary care. Cross-sectional diagnostic study. Primary care. Patients (N=134; age, 18-65y) who consulted their general practitioner (GP) within 5 weeks after injury. Not applicable. Index tests were obtained with a questionnaire and physical examination. Magnetic resonance imaging (MRI) was used as the reference test. Logistic regression analysis was used to determine associations with ACL lesions. Diagnostic accuracy was determined by calculating sensitivity (Se), specificity (Sp), predictive values, and likelihood ratio (LR). MRI showed an ACL lesion in 28 of 134 included patients. "Effusion," "popping sensation," "giving way," and "anterior drawer test (ADT)" showed associations with an ACL lesion (P<.05). Popping sensation showed Se, Sp, positive predictive value (PPV), and positive LR (LR(+)) of .63, .73, .39, and 2.3, respectively. Combining determinants from history taking (2 of 3 positive results regarding effusion, popping sensation, and giving way) improved diagnostic accuracy (Se, .71; Sp, .71; PPV, .42; and LR(+), 2.5). The ADT added diagnostic accuracy to these combinations (Se, .63; Sp, .85; PPV, .52; and LR(+), 4.2). ACL lesions are seen frequently. Based on history taking (effusion, popping sensation, and/or giving way) and physical examination (ADT), GPs can screen for ACL lesions in primary care.

  3. Scanning electron microscopic description of cellular activity and mineral changes in feline odontoclastic resorptive lesions.

    PubMed

    Gauthier, O; Boudigues, S; Pilet, P; Aguado, E; Heymann, D; Daculsi, G

    2001-12-01

    The cellular activity and changes in mineral composition of dental tissues involved in feline odontoclastic resorptive lesions were investigated. Teeth with at least 1 lesion (n = 10) were extracted from 10 different cats that were presented primarily for chronic gingivostomatitis and/or severe periodontal disease. Scanning electron microscopic methods were used to determine the presence of resorptive cells in 8 teeth while 2 teeth were evaluated for pathologic changes in dental mineral composition. Observations were complicated by the presence of organic wear on the dental surfaces, however resorptive cells could be clearly identified in feline odontoclastic resorptive lesions. Resorptive cells had morphologic features indicative of "osteoclast-like" cells or odontoclasts. Resorptive cell activity created a resorption area of darker dentin continuous with physiologic dentin. The darker dentin area seemed poorly mineralized and showed a significantly lower calcium/phosphorous ratio compared with adjacent physiologic denting in 1 tooth. A significantly higher level of magnesium combined with available carbonate ions may have increased the solubility in areas of darker dentin.

  4. Functional activation independently contributes to naming ability and relates to lesion site in post-stroke aphasia.

    PubMed

    Skipper-Kallal, Laura M; Lacey, Elizabeth H; Xing, Shihui; Turkeltaub, Peter E

    2017-04-01

    Language network reorganization in aphasia may depend on the degree of damage in critical language areas, making it difficult to determine how reorganization impacts performance. Prior studies on remapping of function in aphasia have not accounted for the location of the lesion relative to critical language areas. They rectified this problem by using a multimodal approach, combining multivariate lesion-symptom mapping and fMRI in chronic aphasia to understand the independent contributions to naming performance of the lesion and the activity in both hemispheres. Activity was examined during two stages of naming: covert retrieval, and overt articulation. Regions of interest were drawn based on over- and under-activation, and in areas where activity had a bivariate relationship with naming. Regressions then tested whether activation of these regions predicted naming ability, while controlling for lesion size and damage in critical left hemisphere naming areas, as determined by lesion-symptom mapping. Engagement of the right superior temporal sulcus (STS) and disengagement of the left dorsal pars opercularis (dPOp) during overt naming was associated with better than predicted naming performance. Lesions in the left STS prevented right STS engagement and resulted in persistent left dPOp activation. In summary, changes in activity during overt articulation independently relate to naming outcomes, controlling for stroke severity. Successful remapping relates to network disruptions that depend on the location of the lesion in the left hemisphere. Hum Brain Mapp 38:2051-2066, 2017. © 2017 Wiley Periodicals, Inc.

  5. Dental radiography: efficacy in the assessment of intraosseous lesions of the face and jaws in asymptomatic patients

    SciTech Connect

    Zeichner, S.J.; Ruttimann, U.E.; Webber, R.L.

    1987-03-01

    In this investigation the efficacy of dental radiography for the detection of occult intraosseous lesions of the face and jaws was evaluated. An analysis of 30 million health insurance records indicated that the period prevalence of malignant lesions was less than 5 cases/million/year, and for benign lesions approximately 100 cases/million/year. Data from a controlled observer-performance study showed that radiographic sensitivities ranged between 50% and 80%. The cost per true-positive finding was estimated to be +8.6 million per malignant case and +430,000 per benign case. An assessment of the dosimetric literature indicated that the benefits of radiographic screening as a means for early detection of a malignancy appear to be counterbalanced by the risk of causing a radiation-induced malignancy. Taken together, these data demonstrate that dental radiography is not efficacious for the purpose of detecting occult lesions.

  6. Cognitive structure of executive deficits in frontally lesioned head trauma patients performing activities of daily living.

    PubMed

    Fortin, Sandra; Godbout, Lucie; Braun, Claude M J

    2003-04-01

    Executive functions in activities of daily living (ADL) were investigated in 10 patients with frontal lobe lesions after a mild to severe closed head injury (CHI). The CHI patients were compared to 12 normal controls with a neuropsychological test battery, a script recitation task and a realistic simulation of complex multitask ADL (planning and preparing a meal). Though the CHI patients were significantly slow on one test and subject to interference on an attention test with parametric testing, the groups did not differ on any neuropsychological test with non parametric testing. However, the CHI patients manifested marked anomalies in the meal preparation task. While small sequences of actions were easily produced, large action sets could not be correctly executed. An outstanding deficit in strategic planning and prospective memory appears to be an important underpinning of the impairment of ADL observed in CHI patients with frontal lobe lesions.

  7. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  8. Use of micro-computed tomography for the assessment of periapical lesions in small rodents: a systematic review.

    PubMed

    Kalatzis-Sousa, N G; Spin-Neto, R; Wenzel, A; Tanomaru-Filho, M; Faria, G

    2016-03-19

    This systematic review aimed to review the literature on the acquisition-, reconstruction-, and analysis parameters of micro-computed tomography (micro-CT) for the assessment of periapical lesions in rats and mice, and to illustrate the effect of variation in these parameters. The PubMed database was searched from 2000 to January 2015 (English-language publications) for reports on the use of micro-CT to evaluate periapical lesions in rats and mice. QUADAS criteria were used to rate the quality of the studies. To illustrate the effect of variations in acquisition-, reconstruction-, and analysis parameters on images of periapical lesions, micro-CT examination of two hemi-mandibles of mice, with periapical lesions around the first molar was undertaken. Twenty-one studies were identified, which analyzed periapical lesions in rats or mice using micro-CT. According to the QUADAS, no study was classified as high-, seven were classified as moderate-, and 14 as low quality. The effect of variation in parameters was that voxel size may interfere with image sharpness, reconstruction may interfere with image sharpness and contrast, and inadequate plane orientation may alter the size of the periapical lesion. Non-personalized ROIs resulted in areas that were not part of the periapical lesion. Changing the limits of the threshold for bone-tissue visualization increased lesion size. There is no defined protocol for acquiring and analyzing micro-CT images of periapical lesions in rats and mice. Further, acquisition-, reconstruction-, and analysis parameters are not adequately explained, which may compromise the scientific impact of the studies. This article is protected by copyright. All rights reserved.

  9. The significance of reflectance confocal microscopy in the assessment of solitary pink skin lesions.

    PubMed

    Braga, Juliana Casagrande Tavoloni; Scope, Alon; Klaz, Itay; Mecca, Patricia; González, Salvador; Rabinovitz, Harold; Marghoob, Ashfaq A

    2009-08-01

    Solitary pink lesions often manifest nondescript clinical and dermatoscopic primary morphologic features. The differential diagnosis for pink lesions tends, therefore, to be broad, ranging from inflammatory processes to malignancy. In vivo reflectance confocal microscopy (RCM) may help in the evaluation of pink lesions. We sought to demonstrate the use of RCM as an adjunct to the bedside diagnosis of pink lesions. We describe a series of patients with clinically and dermatoscopically equivocal pink lesions for which RCM examination allowed for a rapid and accurate diagnosis. All lesions were excised for histopathologic evaluation. Integrating the findings in the case series with a literature review, we present RCM diagnostic criteria for pink lesions. Lesions included basal cell carcinoma, squamous cell carcinoma, amelanotic melanoma, and inflamed seborrheic keratosis. RCM shows distinctive findings for each diagnostic entity when stratified by anatomic level into suprabasal epidermis, dermoepidermal junction, and papillary dermis. In the cases presented RCM allowed for a rapid and accurate noninvasive diagnosis. The study is descriptive and does not test accuracy of RCM criteria in a prospective series of pink lesions. RCM may add useful diagnostic features to the clinical evaluation of solitary pink lesions.

  10. A phantom design and assessment of lesion detectability in PET imaging

    NASA Astrophysics Data System (ADS)

    Wollenweber, Scott D.; Kinahan, Paul E.; Alessio, Adam M.

    2017-03-01

    The early detection of abnormal regions with increased tracer uptake in positron emission tomography (PET) is a key driver of imaging system design and optimization as well as choice of imaging protocols. Detectability, however, remains difficult to assess due to the need for realistic objects mimicking the clinical scene, multiple lesion-present and lesion-absent images and multiple observers. Fillable phantoms, with tradeoffs between complexity and utility, provide a means to quantitatively test and compare imaging systems under truth-known conditions. These phantoms, however, often focus on quantification rather than detectability. This work presents extensions to a novel phantom design and analysis techniques to evaluate detectability in the context of realistic, non-piecewise constant backgrounds. The design consists of a phantom filled with small solid plastic balls and a radionuclide solution to mimic heterogeneous background uptake. A set of 3D-printed regular dodecahedral `features' were included at user-defined locations within the phantom to create `holes' within the matrix of chaotically-packed balls. These features fill at approximately 3:1 contrast to the lumpy background. A series of signal-known-present (SP) and signal-known-absent (SA) sub-images were generated and used as input for observer studies. This design was imaged in a head-like 20 cm diameter, 20 cm long cylinder and in a body-like 36 cm wide by 21 cm tall by 40 cm long tank. A series of model observer detectability indices were compared across scan conditions (count levels, number of scan replicates), PET image reconstruction methods (with/without TOF and PSF) and between PET/CT scanner system designs using the same phantom imaged on multiple systems. The detectability index was further compared to the noise-equivalent count (NEC) level to characterize the relationship between NEC and observer SNR.

  11. Magnifying endoscopy in upper gastroenterology for assessing lesions before completing endoscopic removal

    PubMed Central

    Chai, Ning-Li; Ling-Hu, En-Qiang; Morita, Yoshinori; Obata, Daisuke; Toyonaga, Takashi; Azuma, Takeshi; Wu, Ben-Yan

    2012-01-01

    Any prognosis of gastrointestinal (GI) cancer is closely related to the stage of the disease at diagnosis. Endoscopic submucosal dissection (ESD) and en bloc endoscopic mucosal resection (EMR) have been performed as curative treatments for many early-stage GI lesions in recent years. The technologies have been widely accepted in many Asian countries because they are minimally invasive and supply thorough histopathologic evaluation of the specimens. However, before engaging in endoscopic therapy, an accurate diagnosis is a precondition to effecting the complete cure of the underlying malignancy or carcinoma in situ. For the past few years, many new types of endoscopic techniques, including magnifying endoscopy with narrow-band imaging (ME-NBI), have emerged in many countries because these methods provide a strong indication of early lesions and are very useful in determining treatment options before ESD or EMR. However, to date, there is no comparable classification equivalent to “Kudo’s Pit Pattern Classification in the colon”, for the upper GI, there is still no clear internationally accepted classification system of magnifying endoscopy. Therefore, in order to help unify some viewpoints, here we will review the defining optical imaging characteristics and the current representative classifications of microvascular and microsurface patterns in the upper GI tract under ME-NBI, describe the accurate relationship between them and the pathological diagnosis, and their clinical applications prior to ESD or en bloc EMR. We will also discuss assessing the differentiation and depth of invasion, defying the lateral spread of involvement and targeting biopsy in real time. PMID:22493543

  12. The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation.

    PubMed

    Jennings, Katie A; Platt, Nicola J; Cragg, Stephanie J

    2015-10-01

    Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD.

  13. Understanding visual search patterns of dermatologists assessing pigmented skin lesions before and after online training.

    PubMed

    Krupinski, Elizabeth A; Chao, Joseph; Hofmann-Wellenhof, Rainer; Morrison, Lynne; Curiel-Lewandrowski, Clara

    2014-12-01

    The goal of this investigation was to explore the feasibility of characterizing the visual search characteristics of dermatologists evaluating images corresponding to single pigmented skin lesions (PSLs) (close-ups and dermoscopy) as a venue to improve training programs for dermoscopy. Two Board-certified dermatologists and two dermatology residents participated in a phased study. In phase I, they viewed a series of 20 PSL cases ranging from benign nevi to melanoma. The close-up and dermoscopy images of the PSL were evaluated sequentially and rated individually as benign or malignant, while eye position was recorded. Subsequently, the participating subjects completed an online dermoscopy training module that included a pre- and post-test assessing their dermoscopy skills (phase 2). Three months later, the subjects repeated their assessment on the 20 PSLs presented during phase I of the study. Significant differences in viewing time and eye-position parameters were observed as a function of level of expertise. Dermatologists overall have more efficient search than residents generating fewer fixations with shorter dwells. Fixations and dwells associated with decisions changing from benign to malignant or vice versa from photo to dermatoscopic viewing were longer than any other decision, indicating increased visual processing for those decisions. These differences in visual search may have implications for developing tools to teach dermatologists and residents about how to better utilize dermoscopy in clinical practice.

  14. Evaluation of virtual touch tissue imaging quantification, a new shear wave velocity imaging method, for breast lesion assessment by ultrasound.

    PubMed

    Golatta, Michael; Schweitzer-Martin, Mirjam; Harcos, Aba; Schott, Sarah; Gomez, Christina; Stieber, Anne; Rauch, Geraldine; Domschke, Christoph; Rom, Joachim; Schütz, Florian; Sohn, Christof; Heil, Jörg

    2014-01-01

    To evaluate virtual touch tissue imaging quantification (VTIQ) as a new elastography method concerning its intra- and interexaminer reliability and its ability to differentiate benign from malignant breast lesions in comparison to and in combination with ultrasound (US) B-mode breast imaging reporting and data system (BI-RADS) assessment. US and VTIQ were performed by two examiners in 103 women with 104 lesions. Intra- and interexaminer reliability of VTIQ was assessed. The area under the receiver operating curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BIRADS, VTIQ, and combined data were compared. Fifty-four of 104 lesions were malignant. Intraexaminer reliability was consistent, and interexaminer agreement showed a strong positive correlation (r = 0.93). The mean VTIQ values in malignant lesions were significantly higher than those in benign (7.73 m/s ± 1.02 versus 4.46 m/s ± 1.87; P < 0.0001). The combination of US-BIRADS with the optimal cut-off for clinical decision making of 5.18 m/s yielded a sensitivity of 98%, specificity of 82%, PPV of 86%, and NPV of 98%. The combination of BIRADS and VTIQ led to improved test validity. VTIQ is highly reliable and reproducible. There is a significant difference regarding the mean maximum velocity of benign and malignant lesions. Adding VTIQ to BIRADS assessment improves the specificity.

  15. Risk model for estimating the 1-year risk of deferred lesion intervention following deferred revascularization after fractional flow reserve assessment.

    PubMed

    Depta, Jeremiah P; Patel, Jayendrakumar S; Novak, Eric; Gage, Brian F; Masrani, Shriti K; Raymer, David; Facey, Gabrielle; Patel, Yogesh; Zajarias, Alan; Lasala, John M; Amin, Amit P; Kurz, Howard I; Singh, Jasvindar; Bach, Richard G

    2015-02-21

    Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  16. Suppression of Neurotoxic Lesion-Induced Seizure Activity: Evidence for a Permanent Role for the Hippocampus in Contextual Memory

    PubMed Central

    Sparks, Fraser T.; Lehmann, Hugo; Hernandez, Khadaryna; Sutherland, Robert J.

    2011-01-01

    Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories. PMID:22110648

  17. Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients.

    PubMed

    Borgogna, Cinzia; Lanfredini, Simone; Peretti, Alberto; De Andrea, Marco; Zavattaro, Elisa; Colombo, Enrico; Quaglia, Marco; Boldorini, Renzo; Miglio, Umberto; Doorbar, John; Bavinck, Jan N Bouwes; Quint, Koen D; de Koning, Maurits N C; Landolfo, Santo; Gariglio, Marisa

    2014-08-01

    The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.

  18. Lesions of the lateral habenula facilitate active avoidance learning and threat extinction.

    PubMed

    Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek

    2017-02-01

    The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes.

  19. Positron emission mammography (PEM): Effect of activity concentration, object size, and object contrast on phantom lesion detection

    SciTech Connect

    MacDonald, Lawrence R.; Wang, Carolyn L.; Eissa, Marna; Haseley, David; Kelly, Mary M.; Liu, Franklin; Parikh, Jay R.; Beatty, J. David; Rogers, James V.

    2012-10-15

    Purpose: To characterize the relationship between lesion detection sensitivity and injected activity as a function of lesion size and contrast on the PEM (positron emission mammography) Flex Solo II scanner using phantom experiments. Methods: Phantom lesions (spheres 4, 8, 12, 16, and 20 mm diameter) were randomly located in uniform background. Sphere activity concentrations were 3 to 21 times the background activity concentration (BGc). BGc was a surrogate for injected activity; BGc ranged from 0.44-4.1 kBq/mL, corresponding to 46-400 MBq injections. Seven radiologists read 108 images containing zero, one, or two spheres. Readers used a 5-point confidence scale to score the presence of spheres. Results: Sensitivity was 100% for lesions {>=}12 mm under all conditions except for one 12 mm sphere with the lowest contrast and lowest BGc (60% sensitivity). Sensitivity was 100% for 8 mm spheres when either contrast or BGc was high, and 100% for 4 mm spheres only when both contrast and BGc were highest. Sphere contrast recovery coefficients (CRC) were 49%, 34%, 26%, 14%, and 2.8% for the largest to smallest spheres. Cumulative specificity was 98%. Conclusions: Phantom lesion detection sensitivity depends more on sphere size and contrast than on BGc. Detection sensitivity remained {>=}90% for injected activities as low as 100 MBq, for lesions {>=}8 mm. Low CRC in 4 mm objects results in moderate detection sensitivity even for 400 MBq injected activity, making it impractical to optimize injected activity for such lesions. Low CRC indicates that when lesions <8 mm are observed on PEM images they are highly tracer avid with greater potential of clinical significance. High specificity (98%) suggests that image statistical noise does not lead to false positive findings. These results apply to the 85 mm thick object used to obtain them; lesion detectability should be better (worse) for thinner (thicker) objects based on the reduced (increased) influence of photon attenuation.

  20. Activity-based cost analysis of contrast-enhanced ultrasonography (CEUS) related to the diagnostic impact in focal liver lesion characterisation.

    PubMed

    Lorusso, Arianna; Quaia, Emilio; Poillucci, Gabriele; Stacul, Fulvio; Grisi, Guido; Cova, Maria Assunta

    2015-08-01

    This study was done to assess the clinical-diagnostic impact and cost of contrast-enhanced ultrasound (CEUS) versus computed tomography (CT) and magnetic resonance (MR) imaging in the characterisation of focal liver lesions. CEUS with sulphur hexafluoride-filled microbubbles (SonoVue bolus 2.4 ml) was performed in 157 patients with 160 focal liver lesions identified by other diagnostic techniques. CEUS images were obtained during the arterial (15 to 35 s from contrast injection), portal venous (40 to 70 s) and late phase (up to 300 s from microbubble injection). Contrast-enhanced CT was performed with a 64-row multidetector CT. MRI was performed before and after administration of the liver-specific contrast agent gadobenate dimeglumine (Gd-BOPTA). A patient-by-patient activity-based cost analysis was performed. CEUS led to a change in the diagnostic workup in 131/157 patients (83.4 %) and in the therapeutic workup in 93/157 patients (59.2 %). CEUS allowed for the final diagnosis to be established in 133/157 patients (84.7 %). The full cost of CEUS was lower than that of contrast-enhanced CT and MR imaging. CEUS determined a change in the diagnostic and therapeutic workup in the characterisation of focal liver lesions and reduced the full costs of the diagnostic process. • CEUS allows a correct diagnosis in more than 80 % of focal liver lesions. • CEUS has a significant impact on the diagnosis of focal liver lesions. • CEUS examination of focal liver lesions reduces total costs. • Dynamic MR with hepato-specific contrast medium remains the reference standard for lesion characterisation. • CEUS is low-cost, versatile and accurate in the characterisation of focal liver lesions.

  1. The effect of retrosplenial cortex lesions in rats on incidental and active spatial learning

    PubMed Central

    Nelson, A. J. D.; Hindley, E. L.; Pearce, J. M.; Vann, S. D.; Aggleton, J. P.

    2015-01-01

    The study examined the importance of the retrosplenial cortex for the incidental learning of the spatial arrangement of distinctive features within a scene. In a modified Morris water-maze, rats spontaneously learnt the location of an escape platform prior to swimming to that location. For this, rats were repeatedly placed on a submerged platform in one corner of either a rectangular (Experiment 1) or square (Experiments 2, 3) pool with walls of different appearance. The rats were then released in the center of the pool for their first test trial. In Experiment 1, the correct corner and its diagonally opposite partner (also correct) were specified by the geometric properties of the pool. Rats with retrosplenial lesions took longer to first reach a correct corner, subsequently showing an attenuated preference for the correct corners. A reduced preference for the correct corner was also found in Experiment 2, when platform location was determined by the juxtaposition of highly salient visual cues (black vs. white walls). In Experiment 3, less salient visual cues (striped vs. white walls) led to a robust lesion impairment, as the retrosplenial lesioned rats showed no preference for the correct corner. When subsequently trained actively to swim to the correct corner over successive trials, retrosplenial lesions spared performance on all three discriminations. The findings not only reveal the importance of the retrosplenial cortex for processing various classes of visuospatial information but also highlight a broader role in the incidental learning of the features of a spatial array, consistent with the translation of scene information. PMID:25705182

  2. Increased expression of interleukin-1 receptor type 1 in active endometriotic lesions.

    PubMed

    Lawson, C; Al-Akoum, M; Maheux, R; Akoum, A

    2007-01-01

    The establishment and progression of ectopic endometrial implants are dependent upon their interaction with and responsiveness to the stimuli present in their new environment. According to our and other previous studies, immune cells-derived cytokines, such as IL-1, may alone or in concert with estrogens, enhance the capability of ectopic endometrial cells to implant and develop into the host tissue. In the present study, immunohistochemical and dual immunofluorescence analyses showed that the functional signaling interleukin-1 receptor type 1 (IL-1RI) is expressed in endometriotic tissue, particularly in the glands, and identified endothelial cells, macrophages, and T-lymphocytes as cells having marked expression of IL-1RI. The highest concentrations of IL-1RI protein in endometriotic tissue, as evaluated using histological score (HSCORE) and measured by ELISA, were found in red endometriotic lesions as compared with typical black-blue or white lesions. Western blotting showed a significant increase in the levels of the 50 kDa band, whose apparent molecular weight corresponds to the soluble form of IL-1RI. RT-PCR analysis of IL-1 mRNA levels showed a pattern of expression comparable to that of the protein. Interestingly, IL-1RI expression was more significant in the proliferative than in the secretory phase of the menstrual cycle. Marked expression of IL-1RI, the functional signaling receptor that mediates cell activation by IL-1, in red endometriotic implants, which are highly vascularized and represent the earliest and most active forms of the disease, point to a higher cell receptivity for IL-1 in these lesions, a relationship with the activity of the disease and a possible involvement in the early steps of endometriotic tissue growth and development.

  3. An In Vitro Assessment of Acoustic Radiation Force Impulse Imaging for Visualizing Cardiac Radiofrequency Ablation Lesions

    PubMed Central

    Eyerly, Stephanie A.; Hsu, Stephen J.; Agashe, Shruti H.; Trahey, Gregg E.; Li, Yang; Wolf, Patrick D.

    2009-01-01

    Introduction Lesion placement and transmurality are critical factors in the success of cardiac transcatheter radiofrequency ablation (RFA) treatments for supraventricular arrhythmias. This study investigated the capabilities of catheter transducer based acoustic radiation force impulse (ARFI) ultrasound imaging for quantifying ablation lesion dimensions. Methods and Results RFA lesions were created in vitro in porcine ventricular myocardium and imaged with an intracardiac ultrasound catheter transducer capable of acquiring spatially registered B-mode and ARFI images. The myocardium was sliced along the imaging plane and photographed. The maximum ARFI-induced displacement images of the lesion were normalized and spatially registered with the photograph by matching the surfaces of the tissue in the B-mode and photographic images. The lesion dimensions determined by a manual segmentation of the photographed lesion based on the visible discoloration of the tissue were compared to automatic segmentations of the ARFI image using two different calculated thresholds. ARFI imaging accurately localized and sized the lesions within the myocardium. Differences in the maximum lateral and axial dimensions were statistically below 2 mm and 1 mm respectively for the two thresholding methods, with mean percent overlap of 68.7±5.21% and 66.3±8.4% for the two thresholds used. Conclusion ARFI imaging is capable of visualizing myocardial RFA lesion dimensions to within 2 mm in vitro. Visualizing lesions during transcatheter cardiac ablation procedures could improve the success of the treatment by imaging lesion line discontinuity and potentially reducing the required number of ablation lesions and procedure time. PMID:20021518

  4. Assessment of oral mucosal lesions among eunuchs residing in Bhopal city, Madhya Pradesh, India: a cross-sectional study.

    PubMed

    Torwane, Nilesh Arjun; Hongal, Sudhir; Goel, Pankaj; Chandrashekar, Byarakele; Saxena, Vrinda

    2015-01-01

    The present cross-sectional study following the STROBE guidelines was conducted to assess the prevalence of oral mucosal lesions among males, females, and eunuchs residing in Bhopal city, Madhya Pradesh India. Based on convenient non-probability snowball sampling technique, all the self-identified eunuchs residing in the city of Bhopal who were present at the time of examination and who fulfilled the selection criteria were examined. A cross section of the general population (males and females) residing in the same locality where these eunuchs live was also examined. The World Health Organization (WHO) oral health assessment proforma (1997) was used to collect the information on oral mucosal lesions. All the obtained data were analyzed by using a Statistical Package for Social Sciences version 20. Overall prevalence of oral mucosal lesions was 127 (19.9%) among the study subjects. Fifty-nine (28.5%) eunuchs, 56 (25.7%) males, and 12 (5.6%) females were observed to have some oral mucosal lesions. Oral submucous fibrosis (6.4%), leukoplakia (5.5%), and traumatic ulceration (4.2%) were the major oral mucosal conditions observed. The information presented in this study adds to our understanding of the common oral mucosal lesions occurring in the eunuch population. Efforts to increase patient awareness of the oral effects of tobacco use and to eliminate the habit are needed to improve the oral and general health of eunuchs.

  5. Activation of PKCα and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain Lesions.

    PubMed

    Yin, Rong; Gao, Lin; Tan, Wenbin; Guo, Wei; Zhao, Tao; Nelson, Jhon Stuart; Wang, Gang

    2017-10-01

    Port wine stain (PWS) is a congenital, progressive vascular malformation. Many patients with PWS develop hypertrophy and discrete nodularity during their adult life, but the mechanism(s) remain incompletely understood. In this study, we attempted to investigate activation status of PKCα, PI3K, PDPK1 and PLC-γ and protein levels of PP2A and DAG to explore their potential roles in the formation of hypertrophic and nodular PWS lesions. We found phosphorylated levels of PKCα, PI3K, PDPK1, and PLC-γ and protein levels of PP2A and DAG showed moderate increases in the endothelial cells of hypertrophic PWS as compared to the adjacent normal skin. These increases extended throughout the entire stroma of blood vessels in PWS nodules. Many proliferating cells, such as fibroblasts, also showed strong activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulations of PP2A and DAG in nodular PWS lesions. Our data showed that there is aberrant activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulation of PP2A and DAG mainly in endothelial cells in hypertrophic PWS areas, but presenting in the entire vasculatures and surrounding fibroblasts in PWS nodules. Our data suggest that both PKCα and PI3K signaling pathways contribute to the development of hypertrophy and nodularity in adult PWS.

  6. An Inhibition of p38 Mitogen Activated Protein Kinase Delays the Platelet Storage Lesion

    PubMed Central

    Skripchenko, Andrey; Awatefe, Helen; Thompson-Montgomery, Dedeene; Myrup, Andrew; Turgeon, Annette; Wagner, Stephen J.

    2013-01-01

    Background and Objectives Platelets during storage undergo diverse alterations collectively known as the platelet storage lesion, including metabolic, morphological, functional and structural changes. Some changes correlate with activation of p38 mitogen activated protein kinase (p38 MAPK). Another MAPK, extracellular signal-related kinase (ERK), is involved in PLT activation. The aim of this study was to compare the properties of platelets stored in plasma in the presence or absence of p38 and ERK MAPK inhibitors. Materials and Methods A single Trima apheresis platelet unit (n = 12) was aliquoted into five CLX storage bags. Two aliquots were continuously agitated with or without MAPK inhibitors. Two aliquots were subjected to 48 hours of interruption of agitation with or without MAPK inhibitors. One aliquot contained the same amount of solvent vehicle used to deliver the inhibitor. Platelets were stored at 20–24°C for 7 days and sampled on Days 1, 4, and 7 for 18 in vitro parameters. Results Inhibition of p38 MAPK by VX-702 leads to better maintenance of all platelet in vitro storage parameters including platelet mitochondrial function. Accelerated by interruption of agitation, the platelet storage lesion of units stored with VX-702 was diminished to that of platelets stored with continuous agitation. Inhibition of ERK MAPK did not ameliorate decrements in any in vitro platelet properties. Conclusion Signaling through p38 MAPK, but not ERK, is associated with platelet deterioration during storage. PMID:23967093

  7. Assessment of the clinical status of primary root carious lesions using an enzymic assay.

    PubMed

    Collier, F I; Heath, M R; Lynch, E; Beighton, D

    1993-01-01

    The microflora of root carious lesions (n = 151) and sound root surfaces (n = 30) in 22 institutionalized, older patients was investigated using a standardized method of sampling. Material was removed using a sterile excavator and the numbers of bacteria in each sample were determined using conventional culturing techniques and by rapid (2 h) fluorogenic enzyme assay. Correlation between bacterial counts and enzyme assay result was 0.873 (p < 0.001). The numbers of bacteria and fluorogenic enzyme assay values were significantly (p < 0.001) greater from soft lesions than from leathery lesions while hard lesions and sound root surfaces had significantly (p < 0.001) lower values than the other lesion types and were not different from each other. A similar trend was apparent when these values were correlated with treatment needs. The fluorogenic enzyme assay may provide a rapid, objective measure of root caries severity which might be used in the monitoring and comparison of treatment protocols.

  8. Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by 1H HR-MAS NMR Metabolomics

    PubMed Central

    Tavel, Laurette; Fontana, Francesca; Garcia Manteiga, Josè Manuel; Mari, Silvia; Mariani, Elisabetta; Caneva, Enrico; Sitia, Roberto; Camnasio, Francesco; Marcatti, Magda; Cenci, Simone; Musco, Giovanna

    2016-01-01

    Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased 1H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions. PMID:27809247

  9. Optical coherence tomography assessment of a complex bifurcation lesion treated with double kissing Crush technique

    PubMed Central

    Cai, Jin-Zan; Zhang, Yao-Jun; Xu, Tian; Zhu, Yong-Xiang; Mao, Chen-Yu; Bourantas, Christos V.; Crake, Tom; Chen, Shao-Liang

    2017-01-01

    Abstract The DEFINITION (Impact of the complexity of bifurcation lesions treated with drug-eluting stents) study has provided a novel classification to evaluate the complexity of coronary bifurcation lesion according to coronary angiography, but angiographic imaging due to its low resolution and inherited limitation may result in an inaccurate adjudication. We used optical coherence tomography (OCT) to further evaluate the coronary characteristics in a patient with “simple” bifurcation lesion which was classified by the DEFINITION criteria. However, a “complex” bifurcation lesion was defined and confirmed according to the OCT results. A double kissing Crush stenting approach was adopted to treat this “complex” case finally. The immediate and long-term angiographic and OCT results were excellent. OCT may be useful imaging modality to classify complexity of coronary bifurcation lesion and subsequently guide its treatment strategy. PMID:28072714

  10. Biomarkers in assessing tubular lesions of the solitary kidney. The solitary kidney in special conditions.

    PubMed

    Gluhovschi, G H; Gadalean, Florica; Gluhovschi, Cristina; Velciov, Silvia; Petrica, Ligia; Timar, R; Anastasiu, D; Gluhovschi, A

    2013-01-01

    The paper highlights the importance of tubular lesions of the solitary kidney (SK), identified and monitored by means of urinary biomarkers, mainly N-acetyl-beta-D-glucosaminidase (NAG), albumin, alpha 1-, and beta 2-microglobulin. It is considered that the assessment of a SK should be performed with four and not three parameters as it was usually done until recently: renal function, proteinuria and blood pressure (BP), to which biomarkers should be added. The solitary kidney can result after nephrectomy for kidney transplantation. In some countries living kidney donors represent the only option for performing kidney transplantation. The SK in living donors has generally a good evolution, although sometimes renal injury manifested by proteinuria, arterial hypertension (AH), or diminution of renal function does occur. Therefore, living donors require attentive monitoring. The SK is considered to have a good evolution (even in donors), in spite of alterations of the above-mentioned clinical and biological parameters. The very infrequent cases who evolve progressively towards renal failure are not predictable, which requires monitoring of all persons with a SK. The SK represents a special situation in case of association with a disease affecting the kidney, such as urinary tract infection (UTI), diabetes mellitus, or systemic lupus erythematosus (SLE). Pregnancy occurring in a person with a SK also needs attentive follow-up. Pregnancy associated diseases, such as preeclampsia occurring in patients with a SK, impose appropriate therapeutic behaviour. The SK remains a particular entity in nephrology which needs to be carefully monitored.

  11. Effects of subcortical cerebrovascular lesions on cortical hemodynamic parameters assessed by perfusion magnetic resonance imaging.

    PubMed

    Nighoghossian, N; Berthezene, Y; Adeleine, P; Wiart, M; Damien, J; Derex, L; Itti, R; Froment, J C; Trouillas, P

    1999-01-01

    A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.

  12. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography.

    PubMed

    Boone, M A L M; Suppa, M; Dhaenens, F; Miyamoto, M; Marneffe, A; Jemec, G B E; Del Marmol, V; Nebosis, R

    2016-01-01

    One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µ raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µ raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma

  13. Color diffusion model for active contours - an application to skin lesion segmentation.

    PubMed

    Ivanovici, Mihai; Stoica, Diana

    2012-01-01

    Most of the existing diffusion models are defined for gray-scale images. We propose a diffusion model for color images to be used as external energy for active contours. Our diffusion model is based on the first-order moment of the correlation integral expressed using ΔE distances in the CIE Lab color space. We use a multi-scale approach for active contours, the diffusion being independently computed at various scales. We validate the model on synthetic images, including multi-fractal color textures, as well as medical images representing melanoma. We conclude that the proposed diffusion model is valid for use in skin lesion segmentation in color images using active contours.

  14. Macrophage migration inhibitory factor is markedly expressed in active and early-stage endometriotic lesions.

    PubMed

    Kats, Rouslan; Metz, Christine N; Akoum, Ali

    2002-02-01

    The establishment of a new vascular supply is essential for the survival of endometrial tissue and its development in ectopic locations. We have previously shown that ectopic endometrial cells release an important mitogenic activity for human endothelial cells and identified macrophage migration inhibitory factor (MIF) as one of the principal bioactive molecules involved in endothelial cell proliferation. In the present study, immunohistochemical and dual immunofluorescence analyses showed that MIF is effectively expressed by endometriotic tissue, particularly in the glands, and identified endothelial cells, macrophages, and T lymphocytes as cells markedly expressing MIF in the stroma. Western blot analysis showed a single 12.5-kDa band corresponding to the known mol wt of the molecule. The highest concentrations of MIF protein in endometriotic tissue, as measured by ELISA, were found in flame-like red endometriotic lesions, compared with typical black-bluish (P < 0.01) or with white lesions (P < 0.01). Interestingly, MIF displayed a marked expression in lesions from the initial stage of endometriosis (stage I). Semiquantitative RT-PCR analysis of MIF mRNA levels in the same endometriotic tissues showed a pattern of expression comparable with that of the protein. In view of its potent proinflammatory and angiogenic properties, local production of MIF within endometrial implants, particularly in those that are highly vascularized and representing the earliest and most active forms of the disease, make plausible the involvement of this factor in the local immunoinflammatory process observed in endometriosis and the initial steps of endometriotic tissue growth and development.

  15. Transgenic Activation of Ras in Neurons Promotes Hypertrophy and Protects from Lesion-Induced Degeneration

    PubMed Central

    Heumann, Rolf; Goemans, Christoph; Bartsch, Daniela; Lingenhöhl, Kurt; Waldmeier, Peter C.; Hengerer, Bastian; Allegrini, Peter R.; Schellander, Karl; Wagner, Erwin F.; Arendt, Thomas; Kamdem, Rigobert H.; Obst-Pernberg, Kirstin; Narz, Frank; Wahle, Petra; Berns, Hartmut

    2000-01-01

    Ras is a universal eukaryotic intracellular protein integrating extracellular signals from multiple receptor types. To investigate its role in the adult central nervous system, constitutively activated V12-Ha-Ras was expressed selectively in neurons of transgenic mice via a synapsin promoter. Ras-transgene protein expression increased postnatally, reaching a four- to fivefold elevation at day 40 and persisting at this level, thereafter. Neuronal Ras was constitutively active and a corresponding activating phosphorylation of mitogen-activated kinase was observed, but there were no changes in the activity of phosphoinositide 3-kinase, the phosphorylation of its target kinase Akt/PKB, or expression of the anti-apoptotic proteins Bcl-2 or Bcl-XL. Neuronal Ras activation did not alter the total number of neurons, but induced cell soma hypertrophy, which resulted in a 14.5% increase of total brain volume. Choline acetyltransferase and tyrosine hydroxylase activities were increased, as well as neuropeptide Y expression. Degeneration of motorneurons was completely prevented after facial nerve lesion in Ras-transgenic mice. Furthermore, neurotoxin-induced degeneration of dopaminergic substantia nigra neurons and their striatal projections was greatly attenuated. Thus, the Ras signaling pathway mimics neurotrophic effects and triggers neuroprotective mechanisms in adult mice. Neuronal Ras activation might become a tool to stabilize donor neurons for neural transplantation and to protect neuronal populations in neurodegenerative diseases. PMID:11134081

  16. A new background distribution-based active contour model for three-dimensional lesion segmentation in breast DCE-MRI

    SciTech Connect

    Liu, Hui; Liu, Yiping; Qiu, Tianshuang; Zhao, Zuowei; Zhang, Lina

    2014-08-15

    Purpose: To develop and evaluate a computerized semiautomatic segmentation method for accurate extraction of three-dimensional lesions from dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) of the breast. Methods: The authors propose a new background distribution-based active contour model using level set (BDACMLS) to segment lesions in breast DCE-MRIs. The method starts with manual selection of a region of interest (ROI) that contains the entire lesion in a single slice where the lesion is enhanced. Then the lesion volume from the volume data of interest, which is captured automatically, is separated. The core idea of BDACMLS is a new signed pressure function which is based solely on the intensity distribution combined with pathophysiological basis. To compare the algorithm results, two experienced radiologists delineated all lesions jointly to obtain the ground truth. In addition, results generated by other different methods based on level set (LS) are also compared with the authors’ method. Finally, the performance of the proposed method is evaluated by several region-based metrics such as the overlap ratio. Results: Forty-two studies with 46 lesions that contain 29 benign and 17 malignant lesions are evaluated. The dataset includes various typical pathologies of the breast such as invasive ductal carcinoma, ductal carcinomain situ, scar carcinoma, phyllodes tumor, breast cysts, fibroadenoma, etc. The overlap ratio for BDACMLS with respect to manual segmentation is 79.55% ± 12.60% (mean ± s.d.). Conclusions: A new active contour model method has been developed and shown to successfully segment breast DCE-MRI three-dimensional lesions. The results from this model correspond more closely to manual segmentation, solve the weak-edge-passed problem, and improve the robustness in segmenting different lesions.

  17. Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

    NASA Astrophysics Data System (ADS)

    Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

    2016-02-01

    Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion.

  18. Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography

    PubMed Central

    Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun

    2016-01-01

    Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion. PMID:26902394

  19. Assessing treatment response of osteolytic lesions by manual volumetry, automatic segmentation, and RECIST in experimental bone metastases.

    PubMed

    Bretschi, Maren; Fränzle, Andrea; Merz, Maximilian; Hillengass, Jens; Semmler, Wolfhard; Bendl, Rolf; Bäuerle, Tobias

    2014-09-01

    Aim of the study was to compare between volumetric and unidimensional approaches for treatment response monitoring in a nude rat model of experimental bone metastases. For the volumetric approach, an automated segmentation algorithm of osteolytic lesions was introduced and compared to manual volumetry. Nude rats bearing osteolytic metastases were treated with zoledronate and sunitinib and compared to controls. Treatment response was assessed longitudinally in vivo using flat-panel volumetric computed tomography at days 30, 35, 45, and 55 after tumor cell inoculation. The mean sizes and volumes of osteolytic lesions were determined according to response evaluation criteria in solid tumors (RECIST) and by automated and manual volumetry (software: MITK [The Medical Imaging Interaction Toolkit, Heidelberg, Germany] and VIRTUOS, Heidelberg, Germany). In contrary to RECIST, the manual volumetric approach indicated a significant decrease in osteolytic lesion volume in response to treatment. The presented automatic segmentation algorithm for treatment monitoring identified bone metastases adequately and assessed changes in the osteolytic lesion volume over time according to manual volumetry. In an animal model, volumetric treatment response assessment of osteolytic bone metastases is superior to unidimensional measurements, and automated volumetric segmentation may be a valuable alternative to manual volume determination. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  20. A pilot study to assess the morphology and progression of non-carious cervical lesions.

    PubMed

    Sugita, Iori; Nakashima, Syozi; Ikeda, Asaomi; Burrow, Michael F; Nikaido, Toru; Kubo, Shisei; Tagami, Junji; Sumi, Yasunori

    2017-02-01

    This longitudinal pilot study aimed to morphologically and quantitatively investigate the progress of non-carious cervical lesions (NCCLs) by using swept-source optical coherence tomography (SS-OCT). The samples examined comprised sets of NCCL epoxy resin replicas obtained from 10 lesions in 6 patients who attended annual dental visits over 4 or 5 years. SS-OCT images of the replicas were analyzed in terms of the maximum depth (Dmax) and corresponding vertical width (VW) - using an image analyzer to estimate progression of the NCCLs over time. It was found that differences between wedge- and saucer-shaped lesions were morphologically distinguished well by the OCT images. There were significant differences in dimensions among Dmax, VW and horizontal width (HW). HW was the largest and Dmax was the smallest. Although no significant differences in absolute values of annual progression rates were found among Dmax, VW and HW, the percentage increase in Dmax was significantly greater compared to VW and HW. The ratios of Dmax to corresponding VW ranged from 0.49 to 1.01 for the wedge-shaped lesions and from 0.13 to 0.44 for saucer-shaped lesions, respectively. The dimensional analysis demonstrated notable progression with large variations. The wedge-shaped lesions appeared to show greater Dmax values compared to the saucer-shaped lesions. With respect to the depth, the wedge-shaped lesions may progress at a greater rate compared to the saucer-shaped lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Assessment of performance and reproducibility of applying a content-based image retrieval scheme for classification of breast lesions

    PubMed Central

    Gundreddy, Rohith Reddy; Tan, Maxine; Qiu, Yuchen; Cheng, Samuel; Liu, Hong; Zheng, Bin

    2015-01-01

    Purpose: To develop a new computer-aided diagnosis (CAD) scheme using a content-based image retrieval (CBIR) approach for classification between the malignant and benign breast lesions depicted on the digital mammograms and assess CAD performance and reproducibility. Methods: An image dataset including 820 regions of interest (ROIs) was used. Among them, 431 ROIs depict malignant lesions and 389 depict benign lesions. After applying an image preprocessing process to define the lesion center, two image features were computed from each ROI. The first feature is an average pixel value of a mapped region generated using a watershed algorithm. The second feature is an average pixel value difference between a ROI’s center region and the rest of the image. A two-step CBIR approach uses these two features sequentially to search for ten most similar reference ROIs for each queried ROI. A similarity based classification score was then computed to predict the likelihood of the queried ROI depicting a malignant lesion. To assess the reproducibility of the CAD scheme, we selected another independent testing dataset of 100 ROIs. For each ROI in the testing dataset, we added four randomly queried lesion center pixels and examined the variation of the classification scores. Results: The area under the ROC curve (AUC) = 0.962 ± 0.006 was obtained when applying a leave-one-out validation method to 820 ROIs. Using the independent testing dataset, the initial AUC value was 0.832 ± 0.040, and using the median classification score of each ROI with five queried seeds, AUC value increased to 0.878 ± 0.035. Conclusions: The authors demonstrated that (1) a simple and efficient CBIR scheme using two lesion density distribution related features achieved high performance in classifying breast lesions without actual lesion segmentation and (2) similar to the conventional CAD schemes using global optimization approaches, improving reproducibility is also one of the challenges in developing

  2. Exogenous activated NK cells enhance trafficking of endogenous NK cells to endometriotic lesions.

    PubMed

    Montenegro, Mary Lourdes; Ferriani, Rui Alberto; Basse, Per H

    2015-08-29

    Endometriosis is defined as the presence of endometrial glands and stroma at ectopic locations. Although the prevalence of endometriosis is as high as 35%-50%, its pathogenesis remains controversial. An increasing number of studies suggest that changes in immune reactivity may be primarily involved in the development of endometriosis development. In this sense, it has been strongly suggested that a fundamental part of immunologic system, the natural killer cells (NK cells), are an important part of this process. NK cells, a component of the innate immune system, have been extensively studied for their ability to defend the organism against infections and malignancy. Recent studies have shown that IL-2-activated NK (A-NK) cells are able to attack and destroy tumors in lungs and livers of mice, demonstrating the therapeutic potential of these cells. Similarly to metastatic tumor cells, endometrial cells are able to adhere, infiltrate and proliferate at ectopic locations. Therefore, in this study, we evaluated the ability of adoptively transferred and endogenous NK cells to infiltrate endometriosis lesions. As NK cells donors were used C57BL/6 B6. PL- Thy 1.1 female mice. As uterine horns donors were used C57/BL6+GFP female mice and as endometriosis recipients C57BL/6 Thy1.2 female mice. Endometriosis induction was made by injection of endometrial tissue fragments. After 4 weeks, necessary for endometriosis lesions establishment the animals were divided in 3 experimental groups with 10 animals each. Group 1 received i.v doses of 5x106 A-NK in 200μl RPMI; Group 2 received i.p dose of 5x106 A-NK in 200μl RPMI and Group 3 received i.p dose of IL2 (0.5 mL RPMI containing 5.000U of IL2). Our data show that exogenous A-NK cells injected via ip combined with endogenous A-NK cells seems to be the most efficient way for activated NK cells track and infiltrate endometriosis. For the first time, it was shown that both endogenous as exogenous A-NK cells are able to track

  3. Assessment of tumor thickness in melanocytic skin lesions: comparison of optical coherence tomography, 20-MHz ultrasound and histopathology.

    PubMed

    Hinz, Torsten; Ehler, Lin-Kristin; Voth, Harald; Fortmeier, Ines; Hoeller, Tobias; Hornung, Thorsten; Schmid-Wendtner, Monika-Hildegard

    2011-01-01

    Accurate assessment of vertical tumor size is important for surgical treatment planning of melanocytic skin lesions. High-frequency ultrasound (HFUS) is frequently used for this purpose, but overestimation of tumor thickness is known as a problem especially in thin melanocytic lesions. Optical coherence tomography (OCT) as a new imaging technique might be a promising alternative. To evaluate the ability of OCT to accurately determine the vertical tumor thickness of melanocytic skin lesions and to compare it with HFUS and histopathology in order to improve surgical planning. In this single-center study, 26 melanocytic lesions were imaged by OCT and HFUS. Vertical lesion dimensions of both methods were compared with histopathological measurements. Bland-Altman plots for OCT and histopathology as well as for HFUS and histopathology revealed better agreement for OCT and histopathology concerning tumor thickness measurements. Tumor thickness values for the melanocytic lesions measured by OCT presented a median tumor thickness of 0.31 mm (range 0.10-0.77) compared to a median tumor thickness of 0.25 mm (range 0.06-1.5) measured by histopathology. The median tumor thickness of HFUS was 0.44 mm (range 0.23-1.1). A Spearman correlation procedure including the correlation coefficient (r) showed a stronger relationship between OCT and histopathology (r = 0.734) compared to HFUS and histopathology (r = 0.390). On the basis of this smaller study cohort, OCT seems to be more exact than HFUS as far as thickness determination of thin melanocytic skin lesions is concerned. Copyright © 2011 S. Karger AG, Basel.

  4. Salt site performance assessment activities

    SciTech Connect

    Kircher, J.F.; Gupta, S.K.

    1983-01-01

    During this year the first selection of the tools (codes) for performance assessments of potential salt sites have been tentatively selected and documented; the emphasis has shifted from code development to applications. During this period prior to detailed characterization of a salt site, the focus is on bounding calculations, sensitivity and with the data available. The development and application of improved methods for sensitivity and uncertainty analysis is a focus for the coming years activities and the subject of a following paper in these proceedings. Although the assessments to date are preliminary and based on admittedly scant data, the results indicate that suitable salt sites can be identified and repository subsystems designed which will meet the established criteria for protecting the health and safety of the public. 36 references, 5 figures, 2 tables.

  5. ERK activation and expression of neuronal cell cycle markers in the hippocampus after entorhinal cortex lesion.

    PubMed

    Hernández-Ortega, Karina; Arias, Clorinda

    2012-11-01

    Current findings suggest that neuronal cell death is frequently associated with the aberrant expression of cell cycle-regulatory proteins in postmitotic neurons. Aberrant cell cycle reentry has been implicated in diverse neurodegenerative conditions, including Alzheimer's disease (AD). Previously we reported that the appearance of cell cycle markers in postmitotic neurons of the entorhinal cortex (EC) after excitotoxic hippocampal damage is associated with the expression of phospho-tau and amyloid precursor protein (APP). However, the question of the signaling pathway involved in this cell cycle reentry remains unresolved. Differentiated neurons use the molecular mechanisms initially acquired to direct cell proliferation, such as the Ras-extracellular signal-regulated kinase (ERK1/2) pathway, to regulate synaptic plasticity. In this work we explored whether ERK1/2-related signaling might contribute to the cell cycle reentry in hippocampal neurons after a unilateral EC lesion. We showed that, within the first 24 hr after hippocampal deafferentation, numerous neurons expressed phospho-ERK1/2, concomitantly with the gradual increases in cyclin D1 and cyclin B immunoreactivity in the dentate gyrus and hilus. Several of these immunopositive cells to phospho-ERK1/2 and cyclin B in hippocampus are postmitotic neurons, insofar as they are positive to NeuN. The intracisternal administration of U0126 (an MEK inhibitor), previous to the excitotoxic lesion, decreased the activation of ERK1/2 and the expression of cyclin D1 and cyclin B in the hippocampus. The present findings support the notion that ERK1/2 plays a role in cell cycle reactivation in mature neurons efferently connected to the lesion site. Copyright © 2012 Wiley Periodicals, Inc.

  6. Assessment of the relationship between lesion segmentation accuracy and computer-aided diagnosis scheme performance

    NASA Astrophysics Data System (ADS)

    Zheng, Bin; Pu, Jiantao; Park, Sang Cheol; Zuley, Margarita; Gur, David

    2008-03-01

    In this study we randomly select 250 malignant and 250 benign mass regions as a training dataset. The boundary contours of these regions were manually identified and marked. Twelve image features were computed for each region. An artificial neural network (ANN) was trained as a classifier. To select a specific testing dataset, we applied a topographic multi-layer region growth algorithm to detect boundary contours of 1,903 mass regions in an initial pool of testing regions. All processed regions are sorted based on a size difference ratio between manual and automated segmentation. We selected a testing dataset involving 250 malignant and 250 benign mass regions with larger size difference ratios. Using the area under ROC curve (A Z value) as performance index we investigated the relationship between the accuracy of mass segmentation and the performance of a computer-aided diagnosis (CAD) scheme. CAD performance degrades as the size difference ratio increases. Then, we developed and tested a hybrid region growth algorithm that combined the topographic region growth with an active contour approach. In this hybrid algorithm, the boundary contour detected by the topographic region growth is used as the initial contour of the active contour algorithm. The algorithm iteratively searches for the optimal region boundaries. A CAD likelihood score of the growth region being a true-positive mass is computed in each iteration. The region growth is automatically terminated once the first maximum CAD score is reached. This hybrid region growth algorithm reduces the size difference ratios between two areas segmented automatically and manually to less than +/-15% for all testing regions and the testing A Z value increases to from 0.63 to 0.90. The results indicate that CAD performance heavily depends on the accuracy of mass segmentation. In order to achieve robust CAD performance, reducing lesion segmentation error is important.

  7. Arrhythmic rats after SCN lesions and constant light differ in short time scale regulation of locomotor activity.

    PubMed

    Chiesa, Juan José; Cambras, Trinitat; Carpentieri, Agata Rita; Díez-Noguera, Antoni

    2010-02-01

    Circadian rhythm disruption (i.e., arrhythmicity) in motor activity is an abnormal behavioral pattern. In rats, it can be caused by the lesion of the hypothalamic suprachiasmatic nucleus (SCN) and by prolonged exposure to constant light (LL). We carried out a comparative study of these arrhythmic phenotypes to assess the role of the SCN in the regulation of the motor output beyond circadian rhythmicity. Motor activity series were studied in rats that had become arrhythmic as a result of 1) LL exposure at 2 light intensities: 300 lux (LL(300)) and 1.3 lux (LL(1.3)), and 2) SCN lesion (SCNx). The Fourier spectra, the fractal Hurst coefficient (H) from the autocorrelation function, and the beta slope from the power spectral density were calculated in data sections at baseline, when the rats were still rhythmic, and later at stages with undetectable circadian rhythms. In the LL(300) group, high power content was detected at frequencies of 8 to 4 h (i.e., ultradian). Lower power content for these harmonics was found in the LL(1.3) group, whereas no dominant harmonics appeared in the SCNx group. Independently of the manifestation of circadian rhythm, H values were higher and more sustained in time in rats exposed to LL( 300) but gradually decreased in rats exposed to LL(1.3). Fractal correlation was found in control DD group but was absent in the SCNx group. We conclude that scale-invariant regulation of the motor pattern by SCN activity is dependent on light intensity but independent of the circadian rhythm output. Adjusting the light intensity by modifying the coupling degree between the population of oscillations could affect the dynamics of each individual oscillator in the SCN, making it less predictable.

  8. Accuracy of CT-guided percutaneous core needle biopsy for assessment of pediatric musculoskeletal lesions.

    PubMed

    Hryhorczuk, Anastasia L; Strouse, Peter J; Biermann, J Sybil

    2011-07-01

    CT-guided percutaneous core needle biopsy has been shown in adults to be an effective diagnostic tool for a large number of musculoskeletal malignancies. To characterize our experience with CT-guided percutaneous core needle biopsy of pediatric bone lesions and determine its utility in diagnosing pediatric osseous lesions, in a population where such lesions are commonly benign. From 2000 to 2009, 61 children underwent 63 CT-guided percutaneous biopsies. Radiological, pathological and clinical records were reviewed. Fourteen biopsies (22%) were performed on malignant lesions, while 49 biopsies (78%) were performed on benign lesions. Forty-nine of the 63 biopsies (78%) were adequate; these children underwent no further tissue sampling. Fourteen of the 63 biopsies (22%) were inadequate or non-conclusive. Of these patients, 12 underwent open biopsy. Retrospective analysis of percutaneous biopsies in these patients demonstrates that 9/12 provided clinically relevant information, and 4/12 patients received final diagnoses that confirmed initial core biopsy findings. No malignancies were diagnosed as benign on percutaneous biopsy. Overall, percutaneous core needle biopsy provided accurate diagnostic information in 84% (53/63) of biopsies. Our results demonstrate that CT-guided percutaneous biopsy is safe and beneficial in children. This study supports the use of CT-guided percutaneous core needle biopsy for primary diagnosis of pediatric bone lesions.

  9. Assessment of Iranian orthodontists' practice with regard to the prevention and treatment of white spot lesions.

    PubMed

    Eslamipour, Faezeh; Shahmoradi, Majid; Farhadi, Vashnad

    2017-01-01

    White spot lesions (WSLs) are common adverse effect of orthodontic treatment, which can be prevented and treated by orthodontists. This study was conducted to assess Iranian orthodontists' practice regarding the prevention and treatment of WSLs in their patients. In this cross-sectional study, 109 Iranian orthodontists were selected from the Iranian Association of Orthodontists' directory by cluster sampling. For data collection, a questionnaire was designed and its validity and reliability was confirmed (Cronbach's α =0.85). The questionnaire included eight general questions and eight questions about practice with regard to the prevention and treatment of WSL. Data were analyzed by descriptive tests, ANOVA test, and t-test in SPSS 20 software. P < 0.05 was considered statistically significant. The mean score of orthodontists' practice was 7.62 (range: 0-8), and 94.4% of the participants were rated as good, while 3.7% and 1.9% were rated as moderate and weak, respectively. Women's score was significantly higher than that of men (P = 0.001). With increasing participants' age, their practice has been improved (P = 0.001), but there was no significant relation between years of experience and their practice (P = 0.230). Nearly 94.4% of the orthodontists prescribed fluoride products. Toothpastes and fluoride mouth rinses were the most common prescribed products (34%). With regard to Iranian orthodontists' practice, it was fortunate to note that majority of the respondents were taking care of their patients with regarding to the prevention and treatment of WSLs. For enhancing their competencies, it is recommended to plan educational courses which are useful for promoting their knowledge and practice about new products and procedures used for the prevention and treatment of WSLs.

  10. A robust region-based active contour model with point classification for ultrasound breast lesion segmentation

    NASA Astrophysics Data System (ADS)

    Liu, Zhihua; Zhang, Lidan; Ren, Haibing; Kim, Ji-Yeun

    2013-02-01

    Lesion segmentation is one of the key technologies for computer-aided diagnosis (CAD) system. In this paper, we propose a robust region-based active contour model (ACM) with point classification to segment high-variant breast lesion in ultrasound images. First, a local signed pressure force (LSPF) function is proposed to classify the contour points into two classes: local low contrast class and local high contrast class. Secondly, we build a sub-model for each class. For low contrast class, the sub-model is built by combining global energy with local energy model to find a global optimal solution. For high contrast class, the sub-model is just the local energy model for its good level set initialization. Our final energy model is built by adding the two sub-models. Finally, the model is minimized and evolves the level set contour to get the segmentation result. We compare our method with other state-of-art methods on a very large ultrasound database and the result shows that our method can achieve better performance.

  11. [The characteristics of a comprehensive geriatric assessment in patients with mild cognitive impairment with a cerebral white matter lesion].

    PubMed

    Obara, Toshimasa; Hasegawa, Hiroshi; Wachi, Yoshitaka; Tanaka, Masamichi; Sato, Michiko; Kobayashi, Yoshio; Koshiba, Hitomi; Nagai, Kumiko; Yamada, Yukiko; Matsui, Toshifumi; Kozaki, Koichi

    2015-01-01

    Vascular dementia may be referred to as "treatable dementia" because its development and progress can be inhibited by intervention in the early stage. In particular, cerebral white matter lesions are readily encountered the clinical setting. In this study, we aimed to clarify the phenomenon and symptoms of patients with mild cognitive impairment (MCI) with cerebral white matter lesions prior to the onset of dementia. The subjects included 181 cases diagnosed with MCI among 643 consecutive new patients of the Center for Comprehensive Care on Memory Disorder at Kyorin University Hospital from January 1, 2013 to January 31, 2014. Patients with particular diseases were excluded. An interview, physical examination, comprehensive geriatric assessment, brain MRI and SPECT were performed for all subjects. The cerebral white matter lesions were evaluated using the modified Fazekas scale. We defined Grades 0 and 1 as the group without apparent cerebral white matter lesions and Grades 2 and 3 as the group with apparent cerebral white matter lesions. We compared the laboratory findings and outcomes of these two groups. The age of the group with apparent cerebral white matter lesions was significantly higher than the group without apparent cerebral white matter lesions (P<0.05). No significant difference was observed regarding gender, MMSE, or "vegetable" term retrieval. A significant difference was observed in the total score and the subordinate component of the 21-item fall risk index and geriatric depression scale between the groups (P<0.05). Additionally, a significant difference was observed regarding the subordinate component of the instrumental ADL, the Dementia Behavior Disturbance Scale and the Zarit Care Burden Scale between the groups (P<0.05). Our results suggest that the presence of white matter lesions at the stage of MCI has a significant relationship to care burden due to the deterioration of ADL, risk of falling, and the presence of depression and behavior

  12. Split-dose technique for FDG PET/CT-guided percutaneous ablation: a method to facilitate lesion targeting and to provide immediate assessment of treatment effectiveness.

    PubMed

    Ryan, E Ronan; Sofocleous, Constantinos T; Schöder, Heiko; Carrasquillo, Jorge A; Nehmeh, Sadek; Larson, Steven M; Thornton, Raymond; Siegelbaum, Robert H; Erinjeri, Joseph P; Solomon, Stephen B

    2013-07-01

    To describe a split-dose technique for fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-guided ablation that permits both target localization and evaluation of treatment effectiveness. Institutional review board approved the study with a waiver of consent. From July to December 2011, 23 patients (13 women, 10 men; mean age, 59 years; range, 35-87 years) with 29 FDG-avid tumors (median size, 1.4 cm; range, 0.6-4.4 cm) were targeted for ablation. The location of the lesion was the liver (n = 23), lung (n = 4), adrenal gland (n = 1), and thigh (n = 1). Radiofrequency ablation was performed in 17 lesions; microwave ablation, in six; irreversible electroporation, in five; and cryoablation, in one. The pathologic condition of the tumor was metastatic colorectal adenocarcinoma in 18 lesions, primary hepatocellular carcinoma in one lesion, and a variety of metastatic tumors in the remaining 10 lesions. A total of 4 mCi (148 MBq) of FDG was administered before the procedure for localization and imaging guidance. At completion of the ablation, an additional 8 mCi (296 MBq) of FDG was administered to assess ablation adequacy. Results of subsequent imaging follow-up were used to determine if postablation imaging after the second dose of FDG reliably helped predict complete tumor ablation. Descriptive statistics were used to summarize the results. Twenty-eight of 29 (97%) ablated lesions showed no residual FDG activity after the second intraprocedural FDG dose. One patient with residual activity underwent immediate biopsy that revealed residual viable tumor and was immediately re-treated. Follow-up imaging at a median of 155 days (range, 92-257 days) after ablation showed local recurrences in two (7%) lesions that were originally negative at postablation PET. Split-dose FDG PET/CT may be a useful tool to provide both guidance and endpoint evaluation, allowing an opportunity for repeat intervention if necessary. Further work is

  13. Consequences of partial and severe dopaminergic lesion on basal ganglia oscillatory activity and akinesia.

    PubMed

    Tseng, Kuei Y; Kargieman, Lucila; Gacio, Sebastian; Riquelme, Luis A; Murer, M Gustavo

    2005-11-01

    Severe chronic dopamine (DA) depletion increases the proportion of neurons in the basal ganglia that fire rhythmic bursts of action potential (LFO units) synchronously with the cortical oscillations. Here we report on how different levels of mesencephalic DA denervation affect substantia nigra pars reticulata (SNpr) neuronal activity in the rat and its relationship to akinesia (stepping test). Chronic nigrostriatal lesion induced with 0 (control group), 4, 6 or 8 microg of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle resulted in a dose-dependent decrease of tyrosine hydroxylase positive (TH+) neurons in the SN and ventral tegmental area (VTA). Although 4 microg of 6-OHDA reduced the number of TH+ neurons in the SN by approximately 60%, both stepping test performance and SNpr neuronal activity remained indistinguishable from control animals. By contrast, animals that received 6 microg of 6-OHDA showed a marked reduction of TH+ cells in the SN ( approximately 75%) and VTA ( approximately 55%), a significant stepping test deficit and an increased proportion of LFO units. These changes were not dramatically enhanced with 8 microg 6-OHDA, a dose that induced an extensive DA lesion (> 95%) in the SN and approximately 70% reduction of DA neurons in the VTA. These results suggest a threshold level of DA denervation for both the appearance of motor deficits and LFO units. Thus, the presence of LFO activity in the SNpr is not related to a complete nigrostriatal DA neuron depletion (ultimate stage parkinsonism); instead, it may reflect a functional disruption of cortico-basal ganglia dynamics associated with clinically relevant stages of the disease.

  14. [Assessment of severity of lesions of arterial basins in patients with multifocal atherosclerosis].

    PubMed

    Sobirov, Zh G; Bakhritdinov, F Sh

    The present study was aimed at working out a methodology combining clinical, haemodynamic, and functional parameters of lesions of arterial basins in patients presenting with concomitant lesions of the aortic arch branches and arteries of lower extremities. The authors retrospectively investigated the results of examining a total of 181 patients operated on for concomitant atherosclerotic lesions of the aortic arch branches, terminal portion of the abdominal aorta, and lower limb arteries. In patients subjected as the first stage to interventions on the aortic arch branches (Group 1), the index of severity of the lesion of the aortic arch branches (Cs) was higher than in those from Groups 2 and 3. In Group 2 patients who as the first stage underwent reconstruction of the terminal portion of the abdominal aorta and lower-limb arteries, the index of severity of lesions of lower limb arteries (Ls) turned out to be higher as compared with patients from Groups 1 and 3. The mean value of the Ls/Cs ratio for Group 1 patients amounted to 1.07, for Group 2 patients to 2.7, and for Group 3 subjects to 1.96. The proposed methodology makes it possible to determine the degree of the lesion of arterial basins in patients suffering from multifocal atherosclerosis and may objectively reflect severity of the lesion thereof. The comparative retrospective analysis has demonstrated that with the Ls/Cs ratio equaling 1.0, the first stage consisted in carrying out an intervention on the aortic arch branches, in the Ls/Cs ratio varying from 2.5 to 3.0, the first stage performed was reconstruction of the terminal portion of the abdominal aorta and arteries of the lower limbs, and cases associated with the Ls/Cs ratio equaling 2 involved simultaneous interventions. A possibility of wide application of the method warrants further investigation.

  15. ACTIVATION OF PPAR GAMMA RECEPTORS REDUCES LEVODOPA-INDUCED DYSKINESIAS IN 6-OHDA-LESIONED RATS

    PubMed Central

    Martinez, A. A.; Morgese, M. G.; Pisanu, A.; Macheda, T.; Paquette, M. A.; Seillier, A.; Cassano, T.; Carta, A.R.; Giuffrida, A.

    2014-01-01

    Long-term administration of L-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson’s disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb and oro-facial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) [1]. In this study, we showed that stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that direct activation of the PPARγ subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268 and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa antiparkinsonian activity. Collectively, these data indicate that PPARγ may represent a new pharmacological target for the treatment of LID. PMID:25486547

  16. NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury.

    PubMed

    Fischer, Marie T; Sharma, Rakhi; Lim, Jamie L; Haider, Lukas; Frischer, Josa M; Drexhage, Joost; Mahad, Don; Bradl, Monika; van Horssen, Jack; Lassmann, Hans

    2012-03-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, and we recently provided evidence for oxidative damage of oligodendrocytes and dystrophic axons in early stages of active multiple sclerosis lesions. In this study, we identified potential sources of reactive oxygen and nitrogen species through gene expression in carefully staged and dissected lesion areas and by immunohistochemical analysis of protein expression. Genome-wide microarrays confirmed mitochondrial injury in active multiple sclerosis lesions, which may serve as an important source of reactive oxygen species. In addition, we found differences in the gene expression levels of various nicotinamide adenine dinucleotide phosphate oxidase subunits between initial multiple sclerosis lesions and control white matter. These results were confirmed at the protein level by means of immunohistochemistry, showing upregulation of the subunits gp91phox, p22phox, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 in activated microglia in classical active as well as slowly expanding lesions. The subunits gp91phox and p22phox were constitutively expressed in microglia and were upregulated in the initial lesion. In contrast, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 expression were more restricted to the zone of initial damage or to lesions from patients with acute or early relapsing/remitting multiple sclerosis. Double labelling showed co-expression of the nicotinamide adenine dinucleotide phosphate oxidase subunits in activated microglia and

  17. NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury

    PubMed Central

    Fischer, Marie T.; Sharma, Rakhi; Lim, Jamie L.; Haider, Lukas; Frischer, Josa M.; Drexhage, Joost; Mahad, Don; Bradl, Monika; van Horssen, Jack

    2012-01-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, and we recently provided evidence for oxidative damage of oligodendrocytes and dystrophic axons in early stages of active multiple sclerosis lesions. In this study, we identified potential sources of reactive oxygen and nitrogen species through gene expression in carefully staged and dissected lesion areas and by immunohistochemical analysis of protein expression. Genome-wide microarrays confirmed mitochondrial injury in active multiple sclerosis lesions, which may serve as an important source of reactive oxygen species. In addition, we found differences in the gene expression levels of various nicotinamide adenine dinucleotide phosphate oxidase subunits between initial multiple sclerosis lesions and control white matter. These results were confirmed at the protein level by means of immunohistochemistry, showing upregulation of the subunits gp91phox, p22phox, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 in activated microglia in classical active as well as slowly expanding lesions. The subunits gp91phox and p22phox were constitutively expressed in microglia and were upregulated in the initial lesion. In contrast, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 expression were more restricted to the zone of initial damage or to lesions from patients with acute or early relapsing/remitting multiple sclerosis. Double labelling showed co-expression of the nicotinamide adenine dinucleotide phosphate oxidase subunits in activated microglia and

  18. Assessment of disease lesion removal as a method to control chronic Montipora white syndrome.

    PubMed

    Beurmann, Silvia; Runyon, Christina M; Videau, Patrick; Callahan, Sean M; Aeby, Greta S

    2017-03-06

    Coral colonies in Kāne'ohe Bay, Hawai'i (USA), are afflicted with the tissue loss disease chronic Montipora white syndrome (cMWS). Here we show that removal of chronic disease lesions is a potential method to slow the progression of cMWS in M. capitata. Over the 24 wk observation period, treatment colonies lost almost half the amount of tissue that was lost by control colonies. The percentage of tissue loss at each sampling interval (mean ± SEM; treatment: 1.17 ± 0.47%, control: 2.25 ± 0.63%) and the rate of tissue loss per day (treatment: 0.13 ± 0.04%, control: 0.27 ± 0.08%) were both significantly lower on treated colonies than control colonies. While lesion removal stopped tissue loss at the initial infection site, which allowed colony healing, it did not prevent re-infection; in all but one of the treated colonies, new cMWS lesions appeared in other areas of the colony but not around the treatment margins. Additionally, the rate of new infections was similar between treatment and control colonies, indicating that physical injury from lesion removal did not appear to increase cMWS susceptibility. These results indicate that lesion removal reduced morbidity in M. capitata exhibiting cMWS but did not stop the disease.

  19. Assessment of HIFU lesions by shear-wave elastography: Initial in-vivo results

    NASA Astrophysics Data System (ADS)

    Anquez, Jeremie; Corréas, Jean-Michel; Criton, Aline; Lacoste, François; Yon, Sylvain

    2012-11-01

    The aim of this work was to evaluate Shear Wave Elastography (SWE) as a tool to visualize HIFU lesions in an acute in-vivo setting. Extracorporeal HIFU sonications of liver were performed on 14 rabbits in 19 consecutive, adjacent pulses, with in situ energies between 75 J and 228 J. A set of images of the sonicated area was acquired prior and post HIFU ablation: 2 orthogonal SWE images (transverse and sagittal) and contrast enhanced CT scan. SWE images were acquired with theAixplorer® device (SuperSonic Imagine, Aix, France). Prior to the treatment, the liver elasticity appeared homogeneous, with a elasticity comprised between 5 and 11 kPa. The lesion extents were manually segmented on post-treatment SWE images and their areas A(SWE)T (transverse) and A(SWE)S (sagittal) were computed. On 3D CT the lesions were segmented as a hypo intense (devascularized) region on 3D CT images, and considered as "ground truth". The transverse and sagittal planes passing by their centers of mass were extracted. The lesion areas were computed for each plane, respectively A(CT)T and A(CT)S. The ratios A(CT)T/A(SWE)T and A(CT)S/A(SWE)S were computed for all the 14 cases. SWE appear to underestimate the lesion extent in the sagittal orientation with respect to CT images, while a good matching is obtained in the transverse orientation.

  20. Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

    PubMed

    Jarjisian, Stephan G; Butler, Matthew P; Paul, Matthew J; Place, Ned J; Prendergast, Brian J; Kriegsfeld, Lance J; Zucker, Irving

    2015-02-01

    The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs. © 2014 The Author(s).

  1. Dorsomedial Hypothalamic Lesions Counteract Decreases in Locomotor Activity in Male Syrian Hamsters Transferred from Long to Short Day Lengths

    PubMed Central

    Paul, Matthew J.; Place, Ned J.; Prendergast, Brian J.; Kriegsfeld, Lance J.; Zucker, Irving

    2015-01-01

    The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs. PMID:25512303

  2. Elevated thymidine phosphorylase activity in psoriatic lesions accounts for the apparent presence of an epidermal growth inhibitor, but is not in itself growth inhibitory

    SciTech Connect

    Hammerberg, C.; Fisher, G.J.; Voorhees, J.J.; Cooper, K.D. )

    1991-08-01

    An apparent tissue-specific growth inhibitor, or chalone, obtained from psoriatic lesions was tentatively identified in the 100-kDa fraction based upon inhibition of DNA synthesis, as measured by (3H)-thymidine uptake by a squamous cell carcinoma cell line, SCC 38. This fraction, however, failed to inhibit SCC 38 cell growth when assessed directly in a neutral red uptake assay. Characterization of the inhibitor of (3H)-thymidine uptake revealed it to have biochemical properties identical to thymidine phosphorylase: (1) molecular weight close to 100 kDa, (2) isoelectric point of 4.2, and (3) thymidine phosphorylase enzyme activity. Thus, the authors conclude that its ability to inhibit (3H)-thymidine uptake was due to thymidine catabolism rather than inhibition of DNA synthesis or growth inhibition. Examination of thymidine phosphorylase activity in keratome biopsies from psoriatic and normal skin demonstrated a twentyfold increase in activity in psoriatic lesions relative to non-lesional or normal skin. This increase in metabolism of thymidine was due to thymidine phosphorylase rather than uridine phosphorylase activity. The correlation between increased thymidine phosphorylase activity and increased keratinocyte proliferation in vitro (cultured) and in vivo (psoriasis), suggests that this enzyme may play a critical role in providing the thymidine necessary for keratinocyte proliferation.

  3. Anti-inflammatory activity of Eugenia punicifolia extract on muscular lesion of mdx dystrophic mice.

    PubMed

    Leite, Paulo Emílio Corrêa; de Almeida, Kessiane Belshoff; Lagrota-Candido, Jussara; Trindade, Pablo; da Silva, Rafael Ferreira; Ribeiro, Manuel Gustavo L; Lima-Araújo, Katia G; Santos, Wilson C; Quirico-Santos, Thereza

    2010-12-15

    Eugenia punicifolia known as "pedra-ume caá" is a shrub largely distributed in the Amazon region popularly used in decoctions or infusions as a natural therapeutic agent, which can interfere on cholinergic nicotinic neurotransmission. This work aimed to investigate a putative anti-inflammatory effect of dichloromethane fraction of E. punicifolia extract (Ep-CM) in the muscular lesion of mdx dystrophic mice, considering that activation of cholinergic mechanisms mitigates inflammation. A polymer containing the Ep-CM was implanted in mdx gastrocnemius muscle before onset of myonecrosis for local slow and gradual release of bioactive compounds and mice sacrificed 7 days or 9 weeks after surgery. Comparing to control muscle, treatment did not alter choline acetyltransferase and acetylcholinesterase enzymatic activities, but decreased metaloproteases-9 and -2 activities and levels of tumor necrosis factor α and NFκB transcription factor. In addition, treatment also reduced levels of bioactive IL-1β form and cleaved caspase-3, related to early events of cellular death and inflammatory activation and further increased myogenin expression without affecting collagen production which is associated with fibrosis. In vivo treatment of mdx dystrophic mice with Ep-CM caused significant reduction of muscular inflammation and improved skeletal muscle regeneration without inducing fibrosis. © 2010 Wiley-Liss, Inc.

  4. The utility of ultrasound in the assessment of traumatic peripheral nerve lesions: report of 4 cases.

    PubMed

    Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D

    2015-09-01

    Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.

  5. Effect of Precompression on the Power Doppler Assessment of Breast Lesion Vascularity.

    PubMed

    DeVita, Robert; Barr, Richard G

    2017-02-01

    To evaluate the effect of precompression on power Doppler visualization of blood flow in breast masses. This Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study evaluated 30 patients with breast masses (16 benign and 14 malignant) undergoing ultrasound-guided breast biopsy. A computational mathematics program was used to calculate the number of color pixels in a region of interest at various degrees of compression of the breast by the transducer. The amount of precompression was calculated as previously described. The percentage of color pixels compared to minimal compression was plotted against the percentage of precompression. The amount of precompression needed to decrease the number of color pixels by 50% and 100% was calculated. The differences between benign and malignant lesions were compared. The mean percentages of precompression ± SD needed to decrease the number of color voxels by 50% in were 15.9% ± 6.43% (range, 8%-30%) for benign lesions and 14.0% ± 4.17% (range, 8%-20%) for malignant lesions (P = .35). The percentages of precompression needed to decrease the number of color pixels by 100% in were 34.7% ± 12.33% (range, 23%-62%) for benign lesions and for malignant lesions 26.7% ± 3.89% (range, 18%-31%), which were statistically significant (P = .027). The amount of precompression normally used when obtaining B-mode images can substantially decrease the number of color voxels on power Doppler sonography. When performing quantitative work on Doppler evaluation of breast lesions, precompression needs to be controlled. © 2016 by the American Institute of Ultrasound in Medicine.

  6. Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping.

    PubMed

    Sprenger, Till; Seifert, Christian L; Valet, Michael; Andreou, Anna P; Foerschler, Annette; Zimmer, Claus; Collins, D Louis; Goadsby, Peter J; Tölle, Thomas R; Chakravarty, M Mallar

    2012-08-01

    Central post-stroke pain of thalamic origin is an extremely distressing and often refractory disorder. There are no well-established predictors for pain development after thalamic stroke, and the role of different thalamic nuclei is unclear. Here, we used structural magnetic resonance imaging to identify the thalamic nuclei, specifically implicated in the generation of central post-stroke pain of thalamic origin. Lesions of 10 patients with central post-stroke pain of thalamic origin and 10 control patients with thalamic strokes without pain were identified as volumes of interest on magnetic resonance imaging data. Non-linear deformations were estimated to match each image with a high-resolution template and were applied to each volume of interest. By using a digital atlas of the thalamus, we elucidated the involvement of different nuclei with respect to each lesion. Patient and control volumes of interest were summed separately to identify unique areas of involvement. Voxelwise odds ratio maps were calculated to localize the anatomical site where lesions put patients at risk of developing central post-stroke pain of thalamic origin. In the patients with pain, mainly lateral and posterior thalamic nuclei were affected, whereas a more anterior-medial lesion pattern was evident in the controls. The lesions of 9 of 10 pain patients overlapped at the border of the ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus. The lesions of this area showed an odds ratio of 81 in favour of developing thalamic pain. The high odds ratio at the ventral posterior nucleus-pulvinar border zone indicates that this area is crucial in the pathogenesis of thalamic pain and demonstrates the feasibility of identifying patients at risk of developing central post-stroke pain of thalamic origin early after thalamic insults. This provides a basis for pre-emptive treatment studies.

  7. Distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions

    PubMed Central

    Serrano, Carmen; Lyahyai, Jaber; Bolea, Rosa; Varona, Luis; Monleón, Eva; Badiola, Juan J.; Zaragoza, Pilar; Martín-Burriel, Inmaculada

    2009-01-01

    Neurodegeneration and gliosis are the main neuropathological features of prion diseases. However, the molecular mechanisms involved in these processes remain unclear. Several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. Here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. Expression changes obtained by real-time RT-PCR were also compared with the extent of classical scrapie lesions, such as prion deposition, neuronal vacuolisation, spongiosis, and astrogliosis as well as with the activation of caspase-3, using a stepwise regression. The results suggest that the factors assessed participate in apoptotic or inflammatory functions, depending on the affected area. The mitochondrial apoptosis pathway was associated with prion deposition in the prefrontal cortex (the less affected area), and with activation of caspase-3-mediated cell death via over-expression of BAK. In addition to its known association with astroglial activation, the extrinsic apoptosis pathway was also related to cell death and neuronal vacuolisation. PMID:19401142

  8. Methodologies for semiquantitative evaluation of hip osteoarthritis by magnetic resonance imaging: approaches based on the whole organ and focused on active lesions.

    PubMed

    Jaremko, Jacob L; Lambert, Robert G W; Zubler, Veronika; Weber, Ulrich; Loeuille, Damien; Roemer, Frank W; Cibere, Jolanda; Pianta, Marcus; Gracey, David; Conaghan, Philip; Ostergaard, Mikkel; Maksymowych, Walter P

    2014-02-01

    As a wider variety of therapeutic options for osteoarthritis (OA) becomes available, there is an increasing need to objectively evaluate disease severity on magnetic resonance imaging (MRI). This is more technically challenging at the hip than at the knee, and as a result, few systematic scoring systems exist. The OMERACT (Outcome Measures in Rheumatology) filter of truth, discrimination, and feasibility can be used to validate image-based scoring systems. Our objective was (1) to review the imaging features relevant to the assessment of severity and progression of hip OA; and (2) to review currently used methods to grade these features in existing hip OA scoring systems. A systematic literature review was conducted. MEDLINE keyword search was performed for features of arthropathy (such as hip + bone marrow edema or lesion, synovitis, cyst, effusion, cartilage, etc.) and scoring system (hip + OA + MRI + score or grade), with a secondary manual search for additional references in the retrieved publications. Findings relevant to the severity of hip OA include imaging markers associated with inflammation (bone marrow lesion, synovitis, effusion), structural damage (cartilage loss, osteophytes, subchondral cysts, labral tears), and predisposing geometric factors (hip dysplasia, femoral-acetabular impingement). Two approaches to the semiquantitative assessment of hip OA are represented by Hip OA MRI Scoring System (HOAMS), a comprehensive whole organ assessment of nearly all findings, and the Hip Inflammation MRI Scoring System (HIMRISS), which selectively scores only active lesions (bone marrow lesion, synovitis/effusion). Validation is presently confined to limited assessment of reliability. Two methods for semiquantitative assessment of hip OA on MRI have been described and validation according to the OMERACT Filter is limited to evaluation of reliability.

  9. Specific and nonspecific multiple unit activities during the onset of pentylenetetrazol seizures. II. Acute lesions interrupting nonspecific system connections.

    PubMed

    Velasco, F; Velasco, M; Maldonado, H; Estrada-Villanueva, F

    1976-12-01

    Nonspecific cortical, thalamic, mesencephalic, and pontine multiple unit activities (MUA) and changes in EEG and MUS of the sciatic nerve after threshold pentylenetetrazol activation were studied in three groups of animals in which neuronal connections were interrupted at three different levels of the central nervous system: spinal, mesencephalic, and prethalamic. Maximal increments of nonspecific MUA and maximal increments and maximal decrements of sciatic MUA after pentylenetetrazol from each group of lesioned animals were statistically compared with tose observed in intact animals. 1. Pentylenetetrazol threshold for producing cortical tonic-clonic EEG discharges was increased in animals with nesencephaic and prethalamic lesions but was not modified in animals with spinal transection. 2. Cortical MUA maximal increment was significantly decreased in mesencephalic and prethalamic lesioned animals, whereas thalamic MUA maximal increment was significantly decreased in mesencephalic and significantly increased in prethalamic lesioned animals. Pontine MUA maximal increment was significantly increased in spinal, mesencephalic, and prethalamic lesioned animals, and mesencephalic M-A maximal increment was not significantly modified in either prethalamic lesioned or in spinal transected animals. 3. Sciatic MUA maximal increment and maximal decrement were significatly decreased in spinal transected animals, whereas only maximal increment was significantly decreased in mesencephalic and only maximal decrement was significantly decreased in prethalamic lesioned animals. These results based on lesion experiments permit us to infer than under normal cinditions the development of generalized seizures induced by threshold pentylenetetrazol injection is highly dependent upon the neuronal interactions between nonspecific structures at different levels of the central nervous system. The possible nature of these neuronal interactions in the intact animals is discussed.

  10. Assessment of macular ganglion cell loss patterns in neurologic lesions that mimic glaucoma.

    PubMed

    Shon, Kilhwan; Sung, Kyung Rim

    2014-08-01

    To evaluate patterns of macular retinal ganglion cell (RGC) loss measured by spectral domain optical coherence tomography in patients with neurologic lesions mimicking glaucoma. We evaluated four patients with neurological lesions who showed characteristic patterns of RGC loss, as determined by ganglion cell thickness (GCT) mapping. Case 1 was a 30-year-old man who had been treated with glaucoma medication. A left homonymous vertical pattern of RGC loss was observed in his GCT map and a past brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion around the right optic radiation. Case 2 was a 72-year-old man with a pituitary adenoma who had a binasal vertical pattern of RGC loss that corresponded with bitemporal hemianopsia. Case 3 was a 77-year-old man treated for suspected glaucoma. His GCT map showed a right inferior quadratic pattern of loss, indicating a right superior homonymous quadranopsia in his visual field (VF). His brain MRI revealed a left posterior cerebral artery territory infarct. Case 4 was a 38-year-old woman with an unreliable VF who was referred for suspected glaucoma. Her GCT map revealed a left homonymous vertical pattern of RGC loss, which may have been related to a previous head trauma. Evaluation of the patterns of macular RGC loss may be helpful in the differential diagnosis of RGC-related diseases, including glaucoma and neurologic lesions. When a patient's VF is unavailable, this method may be an effective tool for diagnosing and monitoring transneuronal retrograde degeneration-related structural changes.

  11. Terahertz pulsed imaging study to assess remineralization of artificial caries lesions

    NASA Astrophysics Data System (ADS)

    Churchley, David; Lynch, Richard J. M.; Lippert, Frank; O'Bryan Eder, Jennifer Susan; Alton, Jesse; Gonzalez-Cabezas, Carlos

    2011-02-01

    We compare terahertz-pulsed imaging (TPI) with transverse microradiography (TMR) and microindentation to measure remineralization of artificial caries lesions. Lesions are formed in bovine enamel using a solution of 0.1 M lactic acid/0.2% Carbopol C907 and 50% saturated with hydroxyapatite adjusted to pH 5.0. The 20-day experimental protocol consists of four 1 min treatment periods with dentifrices containing 10, 675, 1385, and 2700 ppm fluoride, a 4-h/day acid challenge, and, for the remaining time, specimens are stored in a 50:50 pooled human/artificial saliva mixture. Each specimen is imaged at the focal point of the terahertz beam (data-point spacing = 50 μm). The time-domain data are used to calculate the refractive index volume percent profile throughout the lesion, and the differences in the integrated areas between the baseline and post-treatment profiles are used to calculate ΔΔZ(THz). In addition, the change from baseline in both the lesion depth and the intensity of the reflected pulse from the air/enamel interface is determined. Statistically significant Pearson correlation coefficients are observed between TPI and TMR/microindentation (P < 0.05). We demonstrate that TPI has potential as a research tool for hard tissue imaging.

  12. Effect of Irrigant Characteristics on Lesion Formation After Radiofrequency Energy Delivery Using Ablation Catheters with Actively Cooled Tips.

    PubMed

    Nguyen, Duy T; Olson, Matthew; Zheng, Lijun; Barham, Waseem; Moss, Joshua D; Sauer, William H

    2015-07-01

    The delivery of radiofrequency (RF) energy through irrigated ablation catheters may be affected by irrigant osmolarity and by catheter position. We sought to characterize lesion formation characteristics using different irrigants in both open and closed irrigated catheter. An ex vivo model consisting of viable bovine myocardium and a submersible load cell was assembled in a circulating saline bath at 37°C. An externally irrigated ablation catheter and a closed irrigated catheter were positioned with 10 g of force in both perpendicular and parallel positions. A series of ablation lesions using different irrigants were delivered using a constant rate of irrigation (30 cc/min) at 50 W. Potential clinical applicability was evaluated in vivo by targeting porcine epicardium with different irrigants during open irrigation ablation and assessing lesion sizes. Ablation in the perpendicular position produced significantly larger lesions for all irrigants, compared to their respective parallel position ablation. For both open and closed irrigated ablation, half normal saline (HNS) ablation created larger lesions than normal saline (NS), and dextrose water (D5W) lesions were significantly larger than both HNS and NS lesions. Steam pops were mostly observed in the perpendicular position, and the rate of steam pops was statistically higher only for open irrigated D5W, but not for HNS, when compared to NS. Both open and closed irrigated ablation with D5W and HNS in the parallel position created larger lesions than parallel NS ablation without causing more steam pops. In an in vivo porcine model, open irrigated ablation with D5W created larger lesions compared to standard NS irrigation. In ex vivo and in vivo models, decreased osmolarity and charge density increased RF energy delivery to tissue, resulting in larger lesions for both open and closed irrigated ablations. A perpendicular catheter position created larger lesions across all irrigants for both open and closed irrigation

  13. Activation of PPAR gamma receptors reduces levodopa-induced dyskinesias in 6-OHDA-lesioned rats.

    PubMed

    Martinez, A A; Morgese, M G; Pisanu, A; Macheda, T; Paquette, M A; Seillier, A; Cassano, T; Carta, A R; Giuffrida, A

    2015-02-01

    Long-term administration of l-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson's disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb, and orofacial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that the direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) (Morgese et al., 2007). In this study, we showed that the stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that the direct activation of the PPARγ subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268, and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa anti-parkinsonian activity. Collectively, these data indicate that PPARγ may represent a new pharmacological target for the treatment of LID.

  14. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.

    PubMed

    Zivadinov, Robert; Dwyer, Michael; Barkay, Hadas; Steinerman, Joshua R; Knappertz, Volker; Khan, Omar

    2015-03-01

    Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS.

  15. Abnormal cortical functional activity in patients with ischemic white matter lesions: A resting-state functional magnetic resonance imaging study.

    PubMed

    Ding, Xin; Ding, Jurong; Hua, Bo; Xiong, Xingzhong; Xiao, Li; Peng, Fang; Chen, Lin; Pan, Xianfang; Wang, Qingsong

    2017-02-09

    There is increasing evidence that white matter lesions (WMLs) are associated with cognitive impairments. The purpose of this study was to explore the relationship of WMLs with cognitive impairments from the aspect of cortical functional activity. Briefly, Sixteen patients with ischemic WMLs and 13 controls participated in this study. A regional homogeneity (ReHo) approach was used to investigate altered neural coherence in patients with ischemic WMLs during the resting state. A correlation analysis was further performed between regions with altered ReHo and cognitive test scores, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), in the patient group. Finally, we found regions with altered ReHo values in patients with ischemic WMLs to be involved in default mode network (DMN), frontal-parietal control network (FPCN), dorsal attention network (DAN), motor network and right temporal cortex. Moreover, some altered regions belonging to DMN, FPCN and motor network were significantly correlated with cognitive test scores. Our results provide neuroimaging evidence for the impairments of memory, attention, executive and motor function in patients with ischemic WMLs. It is interesting to note that the decreased ReHo was mainly in the anterior brain regions, while increased ReHo in the posterior brain regions, which may indicate a failure down regulation of spontaneous activity in posterior regions. In summary, this study indicates an important role of specific cortical dysfunction in cognitive associated with WMLs.

  16. CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation.

    PubMed

    Sun, Yue; Zhang, Jie; Zhou, Zhou; Wu, Pinru; Huo, Rongfen; Wang, Beiqing; Shen, Zhengyu; Li, Huidan; Zhai, Tianhang; Shen, Baihua; Chen, Xiangdong; Li, Ningli

    2015-11-01

    Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment.

  17. Activity of nigral dopaminergic neurons after lesion of the neostriatum in rats.

    PubMed

    Doudet, D; Gross, C; Seal, J; Bioulac, B

    1984-06-04

    As shown by post-mortem analysis the major neuropathological trait of Huntington's chorea is a degeneration of the intrinsic neurons of the neostriatum (caudate nucleus and putamen). Such a situation can be reproduced by a destruction of the neostriatum by kainic acid. When injected into the caudate nucleus this excitatory amino acid destroys the intrinsic neurons of the neostriatum and spares fairly well the passing fibers. In the present work, we have chosen to examine the influence of neostriatal destruction on the activity of identified dopaminergic cells in the pars compacta of the substantia nigra. As a key element in the nigro-neostriato-nigral loop, this structure is a relevant site for observing the functional effects of neostriatal lesion. Our research hypothesis was based on the generally accepted view that the suppression of the important neostriato-nigral pathway and in particular the inhibitory GABAergic contingent, could generate a hyperactivity of nigral dopaminergic cells. One may therefore consider that the dopaminergic hyperactivity produces abnormal messages which can influence via several pathways the motoneurons, and which participates in the genesis of the hyperkinetic movements characteristic of chorea. After destruction of the neostriatum, we have shown that the pattern of discharge of most identified nigral dopaminergic neurons becomes greatly disorganized. This drastic change in the pattern of activity cannot be interpreted as the simple 'lift of a brake' on these cells by the suppression of the inhibitory GABAergic striato-nigral tract.

  18. Population Based Assessment of MHC Class 1 Antigens Down Regulation as Marker in Increased Risk for Development and Progression of Breast Cancer From Benign Breast Lesions

    DTIC Science & Technology

    2006-01-01

    Development and Progression of Breast Cancer From Benign Breast Lesions PRINCIPAL INVESTIGATOR: Maria J...Population Based Assessment of MHC Class I Antigens Down Regulation as Marker 5a. CONTRACT NUMBER of Increased Risk for Development and...interaction with other epidemiological risk factors that can serve as risk indicators for subsequent development of breast cancer from precancerous lesions

  19. Nontraumatic focal lesions of the spleen: Assessment of imaging and clinical evaluation

    SciTech Connect

    Caslowitz, P.L.; Labs, J.D.; Fishman, E.K.; Siegelman, S.S. )

    1990-03-01

    Fifty-nine cases of nontraumatic splenic disease were reviewed to evaluate the roles of clinical findings, computed tomography, ultrasound, and radionuclide scanning in diagnosis and management. Patient groups included lymphoma (30 patients), infarct (11 patients), abscess (9 patients), cyst (5 patients), hemangioma (3 patients), and hamartoma (1 patient). In no case were clinical findings alone sufficient to diagnose a splenic lesion. Clinical and laboratory manifestations were nonspecific in all groups. Moreover, no radiologic study reliably diagnosed splenic lymphoma or leukemia. All other focal splenic lesions were consistently diagnosed noninvasively. Cross-sectional imaging was more useful than radioisotope scanning, and often provided adjunctive diagnosis of extrasplenic pathology. The superior detail, spatial resolution, and sensitivity of computed tomography made it the single most valuable diagnostic modality.

  20. Lesion correlates of patholinguistic profiles in chronic aphasia: comparisons of syndrome-, modality- and symptom-level assessment.

    PubMed

    Henseler, Ilona; Regenbrecht, Frank; Obrig, Hellmuth

    2014-03-01

    indicate that: (i) Aachen Aphasia Test-based syndrome allocation allows for an unexpectedly concise differentiation between 'Broca's' and 'Wernicke's' aphasia corresponding to non-overlapping anterior and posterior lesion sites; whereas (ii) analyses for modalities and specific symptoms yielded more circumscribed but partially overlapping lesion foci, often cutting across the above syndrome territories; and (iii) especially for lexico-semantic capacities more specialized clinical test-batteries are required to delineate precise lesion patterns at this linguistic level. In sum this is the first report on a successful lesion-delineation of syndrome-based aphasia classification highlighting the relevance of vascular distribution for the syndrome level while confirming and extending a number of more linguistically motivated differentiations, based on clinically used tests. We consider such a comprehensive view reaching from the syndrome to a fine-grained symptom-oriented assessment mandatory to converge neurolinguistic, patholinguistic and clinical-therapeutic knowledge on language-competence and impairment.

  1. Assessment of Total Lesion Glycolysis by (18)F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma.

    PubMed

    McDonald, James E; Kessler, Marcus M; Gardner, Michael W; Buros, Amy F; Ntambi, James A; Waheed, Sarah; van Rhee, Frits; Zangari, Maurizio; Heuck, Christoph J; Petty, Nathan; Schinke, Carolina; Thanendrarajan, Sharmilan; Mitchell, Alan; Hoering, Antje; Barlogie, Bart; Morgan, Gareth J; Davies, Faith E

    2017-04-15

    Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT attenuation correction ((18)F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semiquantitative characterization of metabolic activity (glycolytic phenotype) by calculation of glucose uptake. Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) have the potential to improve the value of this approach and enhance the prognostic value of disease burden measures. This study aims to determine whether TLG and MTV are associated with progression-free survival (PFS) and overall survival (OS), and whether they improve risk assessments such as International Staging System (ISS) stage and GEP70 risk.Experimental Design: 192 patients underwent whole body PET/CT in the Total Therapy 3A (TT3A) trial and were evaluated using three-dimensional region-of-interest analysis with TLG, MTV, and standard measurement parameters derived for all focal lesions with peak SUV above the background red marrow signal.Results: In multivariate analysis, baseline TLG > 620 g and MTV > 210 cm(3) remained a significant factor of poor PFS and OS after adjusting for baseline myeloma variables. Combined with the GEP70 risk score, TLG > 205 g identifies a high-risk-behaving subgroup with poor expected survival. In addition, TLG > 205 g accurately divides ISS stage II patients into two subgroups with similar outcomes to ISS stage I and ISS stage III, respectively.Conclusions: TLG and MTV have significant survival implications at baseline and offer a more precise quantitation of the glycolytic phenotype of active disease. These measures can be assessed more readily than before using FDA-approved software and should be standardized and incorporated into clinical trials moving forward. Clin Cancer Res; 23(8); 1981-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Gastroenteropancreatic neuroendocrine tumors: impact of consistent contrast agent selection on radiologists' confidence in hepatic lesion assessment on restaging MRIs.

    PubMed

    Balthazar, Patricia; Shinagare, Atul B; Tirumani, Sree Harsha; Jagannathan, Jyothi P; Ramaiya, Nikhil H; Khorasani, Ramin

    2017-08-24

    To evaluate the impact of contrast agent selection on radiologists' confidence in assessing liver lesions on follow-up magnetic resonance imaging (MRI) studies in patients with neuroendocrine tumors. This Institutional Review Board-approved, retrospective study performed at a tertiary cancer center and a quaternary care urban academic hospital included all 694 follow-up abdominal MRI studies from 179 patients with gastroenteropancreatic neuroendocrine tumor performed from 01/01/2010 to 05/31/2015. Primary outcome measure was radiologists' confidence in assessing liver lesions on follow-up MRI. MRI reports were reviewed to abstract radiologists' confidence, classified as "equivocal" if any equivocal connotation (mention of limitation due to differences in contrast agent or follow-up recommendation with specific contrast agent) was present; or "unequivocal" if a precise, confident comparison to prior was documented without the use of ambiguous terms. A fellowship-trained radiologist separately evaluated 100 randomly selected reports and images to calculate interobserver agreement with the report classification (equivocal vs. unequivocal) and with the original MRI report, respectively. Chi-square test was used to compare the proportion of equivocal reports when "same" or "different" contrast agent was used for successive examinations. Rates of equivocal reports were higher when different contrast agents were used for successive examinations compared to examinations with same contrast agent (13.2% [21/159] vs. 1.8% [10/535]; p < 0.0001). There was very good interobserver agreement for assessment of radiologist confidence (κ = 0.92 for report review, κ = 0.82 for image review). Consistent use of contrast agent for follow-up MRIs allows more confident assessment of liver lesions in patients with neuroendocrine tumors.

  3. Observer agreement of treatment responses on planar bone scintigraphy in prostate cancer patients: importance of the lesion assessment method.

    PubMed

    Fonager, Randi F; Zacho, Helle D; Albertsen, Signe; Fledelius, Joan; Ejlersen, June A; Christensen, Mette H; Aleksyniene, Ramune; Biurrun Manresa, José A; Petersen, Lars J

    2017-03-01

    The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients. Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans. Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis. Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.

  4. The added value of PET/Ce-CT/DW-MRI fusion in assessment of hepatic focal lesions: PET/Ce-CT/DW-MRI fusion in hepatic focal lesion.

    PubMed

    Salem, Shahenda; Houseni, Mohamed; Zidan, Lamiaa; Kandil, Ahmed

    2015-07-01

    The liver hosts a variety of benign and malignant tumors. Accurate diagnosis can be challenging in certain cases, especially in patients with a history of malignancy or in those with underlying liver pathology, such as cirrhosis. To evaluate the added clinical value of multi-modality liver imaging utilizing PET/Ce-CT/DW-MRI for characterization of hepatic focal lesions (HFL) and compare it with each diagnostic modality when interpreted alone. The study included 35 patients with HFL. They were 7 females & 28 males; their age ranged from 41 to 78years, all patients underwent PET/Ce-CT and DW-MRI scans. Ce-CT, PET and DW-MR images were reviewed independently, and then combined PET/Ce-CT, PET/DW-MRI and PET/Ce-CT/DW-MRI scans were analyzed. The results were correlated with histopathology or clinical/imaging follow-up. The 35 patients had 98 focal lesions. Fifty-three lesions were finally diagnosed as primary hepatocellular carcinoma, 18 lesions were metastases, 7 lesions were lymphoma and 20 lesions were benign. On a patient based analysis; the sensitivity, specificity, PPV, NPV and accuracy were 100%, 67%, 94%, 100% and 94% for PET/Ce-CT compared to 97%, 83%, 97%, 83% and 94 % for DW-MRI, respectively. Combined PET/Ce-CT/DW-MR scans raise those parameters up to 100%. On a lesion based analysis; the sensitivity, specificity, PPV, NPV and accuracy were 94%, 75%, 94%, 75%, 90% for PET/Ce-CT compared to 94%, 95%, 99%, 97% and 94 % for DW-MRI, respectively. All these parameters were 100 % with PET/Ce-CT/DW-MRI. The addition of DW-MRI to PET/Ce-CT is valuable in the characterization of hepatic focal lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. External rotation and active supination CT arthrography for the postoperative evaluation of type II superior labral anterior to posterior lesions.

    PubMed

    Kim, Sae Hoon; Choi, Ja-Young; Yoo, Hye Jin; Hong, Sung Hwan

    2016-01-01

    To evaluate the effectiveness of external rotation and active supination CT arthrography in postoperative evaluation by comparing it with neutral CT arthrography and analyzing its agreement with postoperative clinical results after the repair of type II superior labral anterior to posterior (SLAP) lesions. A total of 25 patients who had undergone CT arthrography in neutral, external rotation and active supination position at least 1 year after the arthroscopic repair of SLAP lesions were enrolled. Two radiologists independently evaluated the status of the repaired SLAP lesions with neutral CT arthrography and then with external rotation and active supination CT arthrography. Five patients had residual symptoms and positive findings upon SLAP-specific examinations. Agreements between the presence of symptoms and radiologic diagnoses based on neutral CT arthrography were insignificant for reader 1 (κ = 0.138, p = n.s.) and significant for reader 2 (κ = 0.328, p = 0.027). However, agreements were highly significant in the analysis following the evaluation of external rotation and active supination CT arthrography for both readers (κ = 0.694, p < 0.001 in reader 1; κ = 0.783, p < 0.001 in reader 2). The presence of contrast-filled gaps between the labrum and glenoid on neutral CT arthrography after SLAP repair is frequent with satisfactory clinical outcomes. Gaps without additional widening upon external rotation and active supination CT arthrography may suggest postoperatively stable biceps anchors, so this new method could minimize the overdiagnosis of recurrent SLAP lesions. Additional gap widening on external rotation and active supination CT arthrography could be related to a true recurrent SLAP lesion and the symptoms of the patients. Case series, Level IV.

  6. Rapamycin-Resistant mTOR Activity Is Required for Sensory Axon Regeneration Induced by a Conditioning Lesion.

    PubMed

    Chen, Weitao; Lu, Na; Ding, Yue; Wang, Yuan; Chan, Leung Ting; Wang, Xu; Gao, Xin; Jiang, Songshan; Liu, Kai

    2016-01-01

    Neuronal mammalian target of rapamycin (mTOR) activity is a critical determinant of the intrinsic regenerative ability of mature neurons in the adult central nervous system (CNS). However, whether its action also applies to peripheral nervous system (PNS) neurons after injury remains elusive. To address this issue unambiguously, we used genetic approaches to determine the role of mTOR signaling in sensory axon regeneration in mice. We showed that deleting mTOR in dorsal root ganglion (DRG) neurons suppressed the axon regeneration induced by conditioning lesions. To establish whether the impact of mTOR on axon regeneration results from functions of mTOR complex 1 (mTORC1) or 2 (mTORC2), two distinct kinase complexes, we ablated either Raptor or Rictor in DRG neurons. We found that suppressing mTORC1 signaling dramatically decreased the conditioning lesion effect. In addition, an injury to the peripheral branch boosts mTOR activity in DRG neurons that cannot be completely inhibited by rapamycin, a widely used mTOR-specific inhibitor. Unexpectedly, examining several conditioning lesion-induced pro-regenerative pathways revealed that Raptor deletion but not rapamycin suppressed Stat3 activity in neurons. Therefore, our results demonstrate that crosstalk between mTOR and Stat3 signaling mediates the conditioning lesion effect and provide genetic evidence that rapamycin-resistant mTOR activity contributes to the intrinsic axon growth capacity in adult sensory neurons after injury.

  7. Persisting PET-CT lesion activity and M. tuberculosis mRNA after pulmonary tuberculosis cure

    PubMed Central

    Malherbe, Stephanus T.; Shenai, Shubhada; Ronacher, Katharina; Loxton, Andre G.; Dolganov, Gregory; Kriel, Magdalena; Van, Tran; Chen, Ray Y.; Warwick, James; Via, Laura E.; Song, Taeksun; Lee, Myungsun; Schoolnik, Gary; Tromp, Gerard; Alland, David; Barry, Clifton E.; Winter, Jill; Walzl, Gerhard

    2016-01-01

    The absence of a gold standard to determine when antibiotics have induced sterilizing cure confounds the development of new approaches to treat pulmonary tuberculosis (PTB). We detected PET-CT imaging response patterns consistent with active disease along with the presence of Mycobacterium tuberculosis mRNA in sputum and bronchoalveolar lavage samples in a substantial proportion of adult, HIV-negative PTB patients after standard 6-month treatment plus one year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of non-resolving and intensifying lesions on PET-CT might indicate ongoing transcription, suggesting that even apparently curative PTB treatment may not eradicate all organisms in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies and better treatment response markers are likely needed for the successful development of improved and shortened PTB treatment strategies. PMID:27595324

  8. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    PubMed Central

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  9. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  10. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  11. [Clinical Study of Rs-EPI DWI to Improve Imaging Quality and Assessment on Intracranial Mass Lesions].

    PubMed

    Zhang, Kai; Xia, Chun-Chao; Yue, Qiang; Guo, Tao; Peng, Wan-Lin; Li, Yu-Ming; Li, Lei; Zhao, Fei; Pu, Jin; Leng, Qi; Li, Zhen-Lin

    2017-05-01

    To explore the clinical value of readout-segmented echo planar imaging (Rs-EPI) sequence in the assessment of intracranial mass lesions compared to the standard single-shot EPI (Ss-EPI) sequence. We included 21 patients with intracranial mass lesions who underwent both Ss-EPI diffusion weighted imaging (DWI) and Rs-EPI DWI at 3.0T MR scanner with a twenty-channel head-neck coil. The quality of images was assessed by two experienced radiologists independently. The differences in image quality between two sequences were analyzed using Wilcoxon signed-rank test. Inter-observer agreements were analyzed using interclass correlation coefficient (ICC) and Kappa test. All objectives were completed on 3.0T MR. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in Rs-EPI DWI were higher than those in Ss-EPI DWI (130.46±49.10 vs. 71.58±30.43, P=0.000; 33.22±18.86 vs. 17.92±18.72, P=0.003). The scores of overall image quality, ghost artifact where next to the paranasal sinuses, mastoid air cells and frontal sinus of Rs-EPI DWI were significantly higher than those of Ss-EPI DWI. Meanwhile, the geometric distortion of anatomical structures of Rs-EPI DWI were significantly lower compared to Ss-EPI DWI sequence (0.016±0.021 vs. 0.037±0.069, P=0.00). The inter-reader and intra-reader agreements for the assessment of qualitative parameters were good [0.74≤Kappa value or ICC≤0.92]. Rs-EPI DWI sequence is a potential technique to improve the imaging quality in the diagnosis of intracranial mass lesions.

  12. Development Activities Locator and Assessment Method (DALAM)

    DTIC Science & Technology

    2013-11-01

    CENTER FOR ARMY ANALYSIS 6001 GOETHALS ROAD FORT BELVOIR, VA 22060-5230 CAA-2012049 DEVELOPMENT ACTIVITIES LOCATOR AND ASSESSMENT METHOD...CONTRACT NUMBER Development Activities Locator and Assessment Method (DALAM) 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...the problem may be more fundamental, in that the design of our projects is flawed. This study, Development Activities Locator and Assessment Method

  13. Agreement of colposcope and gynocular in assessment of cervical lesions by swede score: a randomized, crossover pilot trial.

    PubMed

    Ngonzi, Joseph; Bajunirwe, Francis; Wistrand, Charlotte; Mayanja, Ronald; Altman, Daniel; Thorsell, Malin; Wikström Shemer, Elisabeth Andrea

    2013-10-01

    This study aimed to determine if criterion standard colposcopy could be provided by a pocket-sized battery-driven colposcope, the Gynocular. The study was a randomized, crossover, pilot clinical trial for evaluating agreement of diagnosis of cervical lesions by colposcopy using a standard colposcope and a pocket-sized battery-driven colposcope, the Gynocular, in 69 women positive for visual inspection with acetic acid. Swede scores were used at the time of colposcopy and compared with the final histological diagnosis after directed cervical biopsy. To test the level of agreement between the colposcopy and Gynocular, we calculated the percentage agreement and the κ statistic. We calculated the detection rates of cervical lesions of the Gynocular and a standard colposcope using biopsy results as criterion standards. All included patients also underwent a Pap smear. The level of agreement of Swede score between the Gynocular and colposcope was 70.1% and the κ statistic was 0.65 (p < .001). Biopsy identified 4 women (6.7%) with cervical intraepithelial neoplasia 1 (CIN 1) and 1 woman (1.7%) with CIN 2; 2 women (3.4%) had CIN 3, and 2 women had invasive cervical cancer (CIN 3+). Pap smear detected 2 women (3.1%) with CIN 1 but did not identify any high-grade cervical lesion. Cervicitis was present in 17 (27.4%) of the Pap smears and in 34 (57.6%) of the biopsies. The study shows that in visual inspection with acetic acid-positive women, a battery-driven, pocket-sized colposcope has a significant level of agreement with stationary colposcopy in assessing cervical lesions.

  14. Curcumin protection activities against γ-Rays-induced molecular and biochemical lesions

    PubMed Central

    2013-01-01

    Background Curcumin is a yellow-pigment phenolic compound used as a food spice and has a broad spectrum of antioxidant, anti-carcinogenic, anti-mutagenic and anti-inflammatory properties. Methods Radio-protective efficacy of curcumin; diferuloylmethane (C21H20O6) was evaluated using molecular and biochemical assays in male mice after exposure to 3 Gy γ-rays. Curcumin was given at a dose of 400 μmol/ kg body weight via gastric tubes for 5 following days either pre-, post- or both pre- and post-exposure. Results The incidence of aberrant cells and aberration types (mostly chromatids, breaks and fragments) was reduced with curcumin dosage as compared to irradiated group. Thiobarbituric acid reactive substances (TBARS), hydroperoxide (HP), xanthine oxidase (XO) and apoptotic markers (DNA- fragmentation and caspase-3 activation) were increased significantly, whereas levels of glutathione (GSH) and the enzymatic antioxidants [Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] were significantly depleted in γ-irradiated mice. Curcumin treatments of mice groups including the 5 days pre-irradiation treated group (protected), the 5 days post-irradiation treated group (treated), and the curcumin treated group 5 days pre- and post-irradiation (protracted), have attenuated the liver toxic effects of γ-rays as manifested by reducing the levels of TBARS, HP, XO and DNA fragmentation. Curcumin has also rescued the depletion of GSH and the enzymatic-antioxidant status. Conclusions Curcumin has significant radio-protective and radio-recovery activities in γ-irradiated mice. It has antioxidant potential against γ-rays-induced cytogenetic, molecular and biochemical lesions in mice. PMID:24053347

  15. Curcumin protection activities against γ-rays-induced molecular and biochemical lesions.

    PubMed

    Tawfik, Sameh S; Abouelella, Amira M; Shahein, Yasser E

    2013-09-21

    Curcumin is a yellow-pigment phenolic compound used as a food spice and has a broad spectrum of antioxidant, anti-carcinogenic, anti-mutagenic and anti-inflammatory properties. Radio-protective efficacy of curcumin; diferuloylmethane (C21H20O6) was evaluated using molecular and biochemical assays in male mice after exposure to 3 Gy γ-rays. Curcumin was given at a dose of 400 μmol/ kg body weight via gastric tubes for 5 following days either pre-, post- or both pre- and post-exposure. The incidence of aberrant cells and aberration types (mostly chromatids, breaks and fragments) was reduced with curcumin dosage as compared to irradiated group. Thiobarbituric acid reactive substances (TBARS), hydroperoxide (HP), xanthine oxidase (XO) and apoptotic markers (DNA- fragmentation and caspase-3 activation) were increased significantly, whereas levels of glutathione (GSH) and the enzymatic antioxidants [Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] were significantly depleted in γ-irradiated mice. Curcumin treatments of mice groups including the 5 days pre-irradiation treated group (protected), the 5 days post-irradiation treated group (treated), and the curcumin treated group 5 days pre- and post-irradiation (protracted), have attenuated the liver toxic effects of γ-rays as manifested by reducing the levels of TBARS, HP, XO and DNA fragmentation. Curcumin has also rescued the depletion of GSH and the enzymatic-antioxidant status. Curcumin has significant radio-protective and radio-recovery activities in γ-irradiated mice. It has antioxidant potential against γ-rays-induced cytogenetic, molecular and biochemical lesions in mice.

  16. Inhibitory effects of DA-9601 on ethanol-induced gastrohemorrhagic lesions and gastric xanthine oxidase activity in rats.

    PubMed

    Huh, Keun; Kwon, Tae Hyup; Shin, Uk Sup; Kim, Won Bae; Ahn, Byoung Ok; Oh, Tae Young; Kim, Jung-Ae

    2003-10-01

    The exposure of gastric mucosa to ethanol produces pathological changes such as inflammatory process, hemorrhagic erosions, even acute ulcers. The gastric mucosal lesions accompanied by a significant decrease of gastric blood flow and increase of reactive oxygen species (ROS) implicate a role of xanthine oxidase in ethanol-induced gastric hemorrhagic erosions. DA-9601, a novel antipeptic formulation of extracts of Artemisia asiatica Nakai, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intubation of absolute ethanol (4 g/kg) significantly induced gastrohemorrhagic lesions and lipid peroxidation in the rat stomach. Oral administration of DA-9601 at 40 mg/kg body weight significantly reduced ethanol-induced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of DA-9601 on alcohol-induced xanthine oxidase-type conversion and enzyme activity. The results suggest that alcohol-induced gastric mucosal damage may be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and that the preventive effect of DA-9601 on gastrohemorrhagic lesions would result from its inhibitory action against xanthine oxidase and oxidative stress in alcohol-treated rats.

  17. A 5 year retrospective study of biopsied jaw lesions with the assessment of concordance between clinical and histopathological diagnoses

    PubMed Central

    Peker, Elif; Öğütlü, Faruk; Karaca, İnci Rana; Gültekin, Elif Sibel; Çakır, Merve

    2016-01-01

    Introduction: The jaw can be affected by several lesions that manifest in the oral cavity, but little is known about their distribution patterns in various populations. Aims and Objectives: This study presents the frequency and distribution of biopsied jaw lesions recorded in Faculty of Dentistry and gathers the information including provisional and final diagnosis of the lesions. Material and Methods: Biopsy of 1938 lesions (2008–2013) was reviewed and 1473 lesions were included in this study. The provisional diagnosis and histopathological validations of lesions were compared. Data on the location of the lesion, as well as patient demographics, were also evaluated. The lesions were divided into three major groups as 1 - developmental/reactive and inflammatory lesions of the jaw, 2 - cystic lesion and 3 - tumor and tumor-like lesions. Statistical Analysis: The variables were recorded and analysed using descriptive statistics. Results and Observations: Three hundred and ninety-six lesions were in Group 1 and periapical granuloma was the most frequent diagnosis. Seven hundred and eighty-nine lesions were in Group 2 and the radicular cyst was the most frequent diagnosis. Two hundred and eighty-eight lesions were in Group 3 and the keratocystic odontogenic tumor was the most frequent. Two hundred and ninety-one biopsied lesions were in disagreement with respect to the diagnoses on clinical and histopathological examination. Conclusion: Consequently, a provisional diagnosis of some of the malignant lesions was reactive, inflammatory, cystic or benign lesions, therefore the importance of evaluation of the specimen is emphasized. PMID:27194866

  18. Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in Active American Tegumentary Leishmaniasis Lesions?

    PubMed Central

    Morgado, Fernanda Nazaré; Nascimento, Michelle T. C.; Saraiva, Elvira M.; de Oliveira-Ribeiro, Carla; Madeira, Maria de Fátima; da Costa-Santos, Marcela; Vasconcellos, Erica C. F.; F. Pimentel, Maria Ines; Rosandiski Lyra, Marcelo; Schubach, Armando de Oliveira; Conceição-Silva, Fátima

    2015-01-01

    Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite

  19. Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in Active American Tegumentary Leishmaniasis Lesions?

    PubMed

    Morgado, Fernanda Nazaré; Nascimento, Michelle T C; Saraiva, Elvira M; de Oliveira-Ribeiro, Carla; Madeira, Maria de Fátima; da Costa-Santos, Marcela; Vasconcellos, Erica C F; Pimentel, Maria Ines F; Rosandiski Lyra, Marcelo; Schubach, Armando de Oliveira; Conceição-Silva, Fátima

    2015-01-01

    Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite

  20. Template length, sequence context, and 3 prime -5 prime exonuclease activity modulate replicative bypass of thymine glycol lesions in vitro

    SciTech Connect

    Clark, J.M.; Beardsley G.P. )

    1989-01-24

    cis-Thymine glycol, a product of ionizing radiation damage to DNA, has been introduced quantitatively at a single site into oligonucleotide templates. The ability of DNA polymerases to replicate templates containing thymine glycol was studied by a primer extension assay, and three factors that influence replicative bypass of this lesion in vitro have been identified. These factors include template length, sequence context, and 3{prime}-5{prime} exonuclease activity. Synthesis by the large fragment of DNA polymerase I (Klenow fragment) terminates quantitatively opposite thymine glycol when the template strand extends only two nucleotides beyond the lesion. Significant bypass is observed when the length of the template beyond the lesion is increased to six nucleotides. On the longer templates, the frequency of bypass of the Klenow fragment depends upon the identity of the base immediately 5{prime} to thymine glycol. The extent of bypass is greatest with cytosine and least with adenine at this position. Bypass of thymine glycol lesions by DNA polymerase {alpha}{sub 2} from HeLa cells shows a qualitatively similar dependence upon local sequence context. In contrast, synthesis by T4 DNA polymerase is quantitatively blocked opposite the lesion regardless of template length or DNA sequence context. Synthesis by a mutant Klenow fragment that is deficient in 3{prime}-5{prime} exonuclease activity, or by AMV reverse transcriptase, results in a significant increase in the frequency of bypass. Thus, increased nucleotide turnover at, or beyond, the site of the lesion is likely to contribute significantly to the arrest of synthesis provoked by cis-thymine glycol in vitro.

  1. Genotoxicity and carcinogenicity testing of pharmaceuticals: correlations between induction of DNA lesions and carcinogenic activity.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2010-01-01

    This survey is a compendium of the results of DNA lesions assays (DNA adducts, DNA strand breaks, DNA repair synthesis) and of the results of carcinogenicity assays of 146 pharmaceuticals. Of these drugs, 55 (37.7%) tested negative in both DNA lesions assay(s) and in carcinogenicity assay(s); 65 (44.5%) tested negative in DNA lesions assay(s), but gave a positive response in at least one carcinogenicity assay; 6 (4.1%) tested positive in at least one DNA lesions assay, but negative in carcinogenicity assay(s); 20 (13.7%) tested positive in at least one DNA lesions assay and in at least one carcinogenicity assay. Concerning the predictivity of DNA lesions assays findings for the results of long-term carcinogenesis assays performed in mice, rats or other species, concordance was found to exist for the 46.2% of pharmaceuticals in the case of DNA adducts, for 63.1% in the case of DNA strand breaks, and for 47.3% in the case of DNA repair synthesis (UDS). 2010 Elsevier B.V. All rights reserved.

  2. [Biomechanical changes in and lesions of the lumbosacral spine in horse riding. Magnetic resonance assessment].

    PubMed

    Simonetti, C; Lupoi, D; Di Giambattista, G; Sessa, V; Rosati, M; Orlacchio, A

    1996-05-01

    Spinal injuries account for 5-15% of sport-related traumas. Equestrian sports are considered, together with rugby, motor sport and diving, the riskiest sport for severe spinal injuries. We investigated the biomechanical changes and repeated microtraumas in equitation. We examined with MR the lumbar spines of 12 professional horsewomen and horsemen, 18-51 years old (mean: 33.4 years), belonging to F.I.S.E. (the Italian Federation for Equestrian Sports) and classified as Olympic riders, Senior and Young European riders. An 0.3-T resistive and an 0.2-T permanent magnets with dedicated surface coils were used. We also examined a control group of non-professional healthy volunteers homogeneous by age. MR findings were classified as follows: 1) changes in normal bending and angles of the lumbar spine; 2) injuries and changes in lumbar disks; 3) changes in spinal ligaments; 4) vertebral body injuries. MR was very sensitive in the assessment of all lumbosacral components in all the athletes; besides yielding useful findings to integrate with clinical results, MR also has a predictive value relative to both the continuation of sports activity and the possible damage at the end of it.

  3. New methodology to assess activity status of occlusal caries in primary teeth using laser fluorescence device.

    PubMed

    Braga, Mariana Minatel; de Benedetto, Monique Saveriano; Imparato, Jose Carlos Pettorossi; Mendes, Fausto Medeiros

    2010-01-01

    An in vivo study was conducted to verify the ability of laser fluorescence (LF) to assess the activity status of occlusal caries in primary teeth, using different air-drying times. Occlusal sites (707) were examined using LF (DIAGNOdent) after air-drying for 3 s and 15 s, and the difference between readings (DIF15 s-3 s) was calculated. For concurrent validation of LF, visual criteria-Nyvad (NY) and Lesion Activity Assessment associated with the International Caries Detection and Assessment System (LAA-ICDAS)-were the reference standards for lesion activity. Histological exam using a pH-indicator dye (0.1% methyl red) was performed in 46 exfoliated/extracted teeth for criterion validation. LF readings and DIF15 s-3 s were compared using Kruskall-Wallis and Mann-Whitney tests. Receiver operating characteristic analyses were performed and validity parameters calculated, considering the caries activity assessment. Using NY, active lesions (3 s: 30.0+/-29.3; 15 s: 34.2+/-30.6) presented higher LF readings than inactive lesions (3 s: 17.0+/-16.3; 15 s: 19.2+/-17.3; p<0.05), different from LAA-ICDAS. Active cavitated caries resulted in higher LF readings (3 s: 50.3+/-3.5; 15 s: 54.7+/-30.2) than inactive cavitated caries (3 s: 19.9+/-16.3; 15 s: 22.8+/-16.8). Therefore, LF can distinguish cavitated active and inactive lesions classified by NY, but not by LAA-ICDAS; however, this difference might be related to the visual system rather than to LF. The air-drying time could be an alternative to improve the caries activity assessment; however, longer air-drying time is suggested to be tested subsequently.

  4. New methodology to assess activity status of occlusal caries in primary teeth using laser fluorescence device

    NASA Astrophysics Data System (ADS)

    Braga, Mariana Minatel; Saveriano de Benedetto, Monique; Imparato, Jose Carlos Pettorossi; Mendes, Fausto Medeiros

    2010-07-01

    An in vivo study was conducted to verify the ability of laser fluorescence (LF) to assess the activity status of occlusal caries in primary teeth, using different air-drying times. Occlusal sites (707) were examined using LF (DIAGNOdent) after air-drying for 3 s and 15 s, and the difference between readings (DIF15 s-3 s) was calculated. For concurrent validation of LF, visual criteria-Nyvad (NY) and Lesion Activity Assessment associated with the International Caries Detection and Assessment System (LAA-ICDAS)-were the reference standards for lesion activity. Histological exam using a pH-indicator dye (0.1% methyl red) was performed in 46 exfoliated/extracted teeth for criterion validation. LF readings and DIF15 s-3 s were compared using Kruskall-Wallis and Mann-Whitney tests. Receiver operating characteristic analyses were performed and validity parameters calculated, considering the caries activity assessment. Using NY, active lesions (3 s: 30.0+/-29.3 15 s: 34.2+/-30.6) presented higher LF readings than inactive lesions (3 s: 17.0+/-16.3 15 s: 19.2+/-17.3 p<0.05), different from LAA-ICDAS. Active cavitated caries resulted in higher LF readings (3 s: 50.3+/-3.5 15 s: 54.7+/-30.2) than inactive cavitated caries (3 s: 19.9+/-16.3 15 s: 22.8+/-16.8). Therefore, LF can distinguish cavitated active and inactive lesions classified by NY, but not by LAA-ICDAS; however, this difference might be related to the visual system rather than to LF. The air-drying time could be an alternative to improve the caries activity assessment; however, longer air-drying time is suggested to be tested subsequently.

  5. Role of primary motor cortex in the control of manual dexterity assessed via sequential bilateral lesion in the adult macaque monkey: A case study.

    PubMed

    Savidan, Julie; Kaeser, Mélanie; Belhaj-Saïf, Abderraouf; Schmidlin, Eric; Rouiller, Eric M

    2017-08-15

    From a case study, we describe the impact of unilateral lesion of the hand area in the primary motor cortex (M1) on manual dexterity and the role of the intact contralesional M1 in long-term functional recovery. An adult macaque monkey performed two manual dexterity tasks: (i) "modified Brinkman board" task, assessed simple precision grip versus complex precision grip, the latter involved a hand postural adjustment; (ii) "modified Klüver board" task, assessed movements ranging from power grip to precision grip, pre-shaping and grasping. Two consecutive unilateral M1 lesions targeted the hand area of each hemisphere, the second lesion was performed after stable, though incomplete, functional recovery from the primary lesion. Following each lesion, the manual dexterity of the contralesional hand was affected in a comparable manner, effects being progressively more deleterious from power grip to simple and then complex precision grips. Both tasks yielded consistent data, namely that the secondary M1 lesion did not have a significant impact on the recovered performance from the primary M1 lesion, which took place 5months earlier. In conclusion, the intact contralesional M1 did not play a major role in the long-term functional recovery from a primary M1 lesion targeted to the hand area. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. mHealth App for Risk Assessment of Pigmented and Nonpigmented Skin Lesions-A Study on Sensitivity and Specificity in Detecting Malignancy.

    PubMed

    Thissen, Monique; Udrea, Andreea; Hacking, Michelle; von Braunmuehl, Tanja; Ruzicka, Thomas

    2017-05-31

    With the advent of smartphone devices, an increasing number of mHealth applications that target melanoma identification have been developed, but none addresses the general context of melanoma and nonmelanoma skin cancer identification. In this study a smartphone application using fractal and classical image analysis for the risk assessment of skin lesions is systematically evaluated to determine its sensitivity and specificity in the diagnosis of melanoma and nonmelanoma skin cancer along with actinic keratosis and Bowen's disease. In the Department of Dermatology, Catharina Hospital Eindhoven, The Netherlands, 341 melanocytic and nonmelanocytic lesions were imaged using SkinVision app; 239 underwent histopathological examination, while the rest of 102 lesions were clinically diagnosed as clearly benign and not removed. The algorithm has been calibrated using the images of the first 233 lesions. The calibrated version of the algorithm was used in a subset of 108 lesions, and the obtained results were compared with the medical findings. On the 108 cases used for evaluation the algorithm scored 80% sensitivity and 78% specificity in detecting (pre)malignant conditions. Although less accurate than the dermatologist's clinical eye, the app may offer support to other professionals who are less familiar with differentiating between benign and malignant lesions. An mHealth application for the risk assessment of skin lesions was evaluated. It adds value to diagnosis tools of its type by taking into consideration pigmented and nonpigmented lesions all together and detecting signs of malignancy with high sensitivity.

  7. Physical Activity Assessments for Individuals with Disabilities

    ERIC Educational Resources Information Center

    Fittipaldi-Wert, Jeanine; Brock, Sheri J.

    2006-01-01

    Physical activity is important in maintaining and improving overall health for all. Students with disabilities tend to have lower fitness levels due to the lack of participation in physical activities, therefore, progressions and modifications to physical activities are needed. Assessing the physical activity levels of students with disabilities…

  8. Prestige in Interest Activity Assessment

    ERIC Educational Resources Information Center

    Sodano, Sandro M.; Tracey, Terence J. G.

    2008-01-01

    Prestige has been demonstrated to be a component in interest assessment [Tracey, T. J. G. (1997). The structure of interests and self-efficacy expectations: An expanded examination of the spherical model of interests. "Journal of Counseling Psychology", 44, 32-43; Tracey, T. J. G. (2002). Personal Globe Inventory: Measurement of the spherical…

  9. PPARalpha, but not PPARgamma, activators decrease macrophage-laden atherosclerotic lesions in a nondiabetic mouse model of mixed dyslipidemia.

    PubMed

    Hennuyer, Nathalie; Tailleux, Anne; Torpier, Gérard; Mezdour, Hafid; Fruchart, Jean-Charles; Staels, Bart; Fiévet, Catherine

    2005-09-01

    Peroxisome proliferator-activated receptor (PPAR) alpha and gamma are nuclear receptors that may modulate atherogenesis, not only by correcting metabolic disorders predisposing to atherosclerosis but also by directly acting at the level of the vascular wall. The accumulation of lipid-laden macrophages in the arterial wall is an early pivotal event participating in the initiation and promotion of atherosclerotic lesion formation. Because PPARalpha and gamma modulate macrophage gene expression and cellular function, it has been suggested that their ligands may modulate atherosclerosis development via direct effects on macrophages. In this report, we investigated the effect of a PPARalpha ligand (fenofibrate) and 2 PPARgamma ligands (rosiglitazone and pioglitazone) on atherogenesis in a dyslipidemic nondiabetic murine model that develops essentially macrophage-laden lesions. Mice were fed a Western diet supplemented or not with fenofibrate (100 mpk), rosiglitazone (10 mpk), or pioglitazone (40 mpk) for 10 weeks. Atherosclerotic lesions together with metabolic parameters were measured after treatment. Fenofibrate treatment significantly improved lipoprotein metabolism toward a less atherogenic phenotype but did not affect insulin sensitivity. Contrarily, rosiglitazone and pioglitazone improved glucose homeostasis, whereas they did not improve lipoprotein metabolism. Fenofibrate treatment significantly decreased the accumulation of lipids and macrophages in the aortic sinus. However, surprisingly, neither rosiglitazone nor pioglitazone had an effect on lesion lipid accumulation or macrophage content. These results indicate that in a dyslipidemic nondiabetic murine model, PPARalpha, but not PPARgamma, activators protect against macrophage foam cell formation.

  10. General dentists', pediatric dentists', and endodontists' diagnostic assessment and treatment strategies for deep carious lesions: A comparative analysis.

    PubMed

    Koopaeei, Mahshid Majlessi; Inglehart, Marita R; McDonald, Neville; Fontana, Margherita

    2017-02-01

    There is a large variation among clinicians when managing deep carious lesions (DCLs). The purpose of this study was to assess general dentists' (GDs), pediatric dentists' (PDs), and endodontists' (EDs) diagnostic methods, clinical decision-making considerations, treatment strategies, and knowledge, behavior, and attitudes related to the diagnosis and treatment of DCLs. A total of 175 GDs, 511 PDs, and 377 EDs responded to a nationwide Web-based survey. Most EDs (68%) and GDs (47%) practiced complete caries removal. PDs (31%) were more likely than GDs (12%) and EDs (4%) to remove carious tissues partially. Dentin hardness was the most important diagnostic criterion used during caries excavation (GDs, 90%; PDs, 72%; EDs, 88%). Only 30% of GDs, 17% of PDs, and 90% of EDs used diagnostic tests (for example, a cold test) when assessing pupal health. A substantial percentage of respondents considered endodontic treatment as a choice for treating DCLs in asymptomatic teeth in young patients (GDs, 40%; PDs, 30%; EDs, 40%). GDs rarely used a rubber dam when treating these lesions. Most respondents practiced complete caries removal until hard dentin was felt, using hardness as the primary excavation criterion, and did not use pulp diagnostic tests routinely before making decisions about treatment of teeth with DCLs. Efforts should be made to translate the growing body of evidence supporting the use of conservative caries removal criteria to preserve pulpal health and tooth structure integrity when managing DCLs. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

  11. Active implant peri-apical lesion: a case report treated via guided bone regeneration with a 5-year clinical and radiographic follow-up.

    PubMed

    Quaranta, Alessandro; Andreana, Sebastiano; Pompa, Giorgio; Procaccini, Maurizio

    2014-06-01

    Implant peri-apical lesion (IPL) is a periapical lesion, usually asymptomatic, in which the coronal portion of the implant achieves a normal bone to implant interface. A case of IPL following immediate implant placement and treated with guided bone regeneration (GBR) principles is described. Five-year clinical and radiographic follow-up with cone-beam assessment showed complete healing of the bone. GBR principles applied to IPL could completely solve the lesion.

  12. Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

    PubMed Central

    Rafacho, Bruna Paola Murino; Stice, Camilla Peach; Liu, Chun; Greenberg, Andrew S.; Ausman, Lynne M.

    2015-01-01

    Background Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. Methods C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. Results DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Conclusions Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway. PMID:26005679

  13. Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

    PubMed Central

    Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

    2016-01-01

    INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

  14. Methylseleninic acid super-activates p53-senescence cancer progression barrier in prostate lesions of Pten-knockout mouse

    PubMed Central

    Wang, Lei; Guo, Xiaolan; Wang, Ji; Jiang, Cheng; Bosland, Maarten C.; Lü, Junxuan; Deng, Yibin

    2015-01-01

    Monomethylated selenium (MM-Se) forms that are precursors of methylselenol such as methylseleninic acid (MSeA) differ in metabolism and anti-cancer activities in preclinical cell and animal models from seleno-methionine that had failed to exert preventive efficacy against prostate cancer (PCa) in North American men. Given that human PCa arises from precancerous lesions such as high-grade prostatic intraepithelial neoplasia (HG-PIN) which frequently have lost PTEN tumor suppressor permitting AKT oncogenic signaling, we tested the efficacy of MSeA to inhibit HG-PIN progression in Pten prostate specific knockout (KO) mice and assessed the mechanistic involvement of p53-mediated cellular senescence and of the androgen receptor (AR). We observed that short-term (4 weeks) oral MSeA treatment significantly increased expression of P53 and P21Cip1 proteins and senescence-associated-β-galactosidase staining, and reduced Ki-67 cell proliferation index in Pten KO prostate epithelium. Long-term (25 weeks) MSeA administration significantly suppressed HG-PIN phenotype, tumor weight, and prevented emergence of invasive carcinoma in Pten KO mice. Mechanistically, the long-term MSeA treatment not only sustained P53-mediated senescence, but also markedly reduced AKT phosphorylation and AR abundance in the Pten KO prostate. Importantly, these cellular and molecular changes were not observed in the prostate of wild type littermates which were similarly treated with MSeA. Since p53 signaling is likely to be intact in HG-PIN compared to advanced PCa, the selective super-activation of p53-mediated senescence by MSeA suggests a new paradigm of cancer chemoprevention by strengthening a cancer progression barrier through induction of irreversible senescence with additional suppression of AR and AKT oncogenic signaling. PMID:26511486

  15. In Situ complement activation and T-cell immunity in leprosy spectrum: An immunohistological study on leprosy lesional skin.

    PubMed

    Bahia El Idrissi, Nawal; Iyer, Anand M; Ramaglia, Valeria; Rosa, Patricia S; Soares, Cleverson T; Baas, Frank; Das, Pranab K

    2017-01-01

    Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition worsens often during and long after treatment. Clearance of bacterial antigens including lipoarabinomannan (LAM) during and after treatment in leprosy patients is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves by in situ generation of the membrane attack complex (MAC). Investigating the role of complement activation in skin lesions of leprosy patients might provide insight into the dynamics of in situ immune reactivity and the destructive pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy patients, whether M. leprae antigen LAM deposition correlates with the deposition of complement activation products MAC and C3d on nerves and cells in the surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n = 6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The percentage of C3d, MAC and LAM deposition was significantly higher in the skin biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p = <0.001 and p = <0.001 respectively), with a significant association between LAM and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001 and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary patients, MAC deposition was found on axons and co-localizing with LAM. In skin lesions of paucibacillary patients, we found C3d positive T-cells in and surrounding granulomas, but hardly any MAC deposition. In addition, MAC immunoreactivity was increased in both ENL and RR skin lesions compared to non-reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present findings demonstrate that complement is deposited in skin lesions of leprosy patients, suggesting that inflammation driven by complement activation might contribute to nerve damage in the lesions of

  16. Anti-inflammatory activity and gastric lesions induced by zinc-tenoxicam.

    PubMed

    Nascimento, Jorge Willian L; Santos, Luiz Henrique; Nothenberg, Michael S; Coelho, Márcio M; Oga, Seizi; Tagliati, Carlos A

    2003-06-01

    Oral administration of tenoxicam or zinc-tenoxicam complex inhibited to a similar extent carrageenin-induced paw oedema and granulomatous tissue formation in rats as well as the acetic acid induced writhing response in mice. Gastric lesions induced by oral administration of zinc-tenoxicam were reduced in number and severity when compared with those induced by tenoxicam or the co-administration of tenoxicam and zinc acetate. However, after intraperitoneal administration, both zinc-tenoxicam and tenoxicam plus zinc acetate induced a reduced number of gastric lesions as compared with tenoxicam.

  17. Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.

    PubMed

    Petrovic, Jelena; Ciric, Jelena; Lazic, Katarina; Kalauzi, Aleksandar; Saponjic, Jasna

    2013-09-01

    The pedunculopontine tegmental nucleus (PPT) represents a major aggregation of cholinergic neurons in the mammalian brainstem, which is important in the generation and maintenance of REM sleep. We investigated the effects of unilateral and bilateral PPT lesions on sleep and all the conventional sleep-state related EEG frequency bands amplitudes, in an attempt to find the EEG markers for the onset and progression of PPT cholinergic neuronal degeneration. The experiments were performed on 35 adult male Wistar rats, chronically implanted for sleep recording. During the surgical procedure for EEG and EMG electrodes implantation, the unilateral or bilateral PPT lesion was produced under ketamine/diazepam anesthesia, by the stereotaxically guided microinfusion of 100 nl 0.1M ibotenic acid (IBO) into PPT. We applied Fourier analysis to signals acquired throughout 6h of recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We also calculated the group probability density estimates (PDE) of all Wake, NREM and REM conventional EEG frequency amplitudes, and the number of all the transition states using MATLAB 6.5. Our results show that the unilateral or bilateral PPT lesions did not change the sleep/wake architecture, but did change the sleep/wake state transitions structure and the sleep/state related "EEG microstructure". Unilateral or bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions from 14 to 35 days after lesions. This was followed by decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion. The unilateral PPT lesion augmented both Wake theta and REM beta while it also attenuated the relative amplitude of the Wake delta frequency, with a delay of one week. Following a bilateral PPT lesion there was augmentation of the relative amplitude of the Wake, NREM, and REM beta and REM gamma frequency which occurred simultaneously to NREM and Wake delta attenuation. We have shown

  18. Rapamycin-Resistant mTOR Activity Is Required for Sensory Axon Regeneration Induced by a Conditioning Lesion

    PubMed Central

    Lu, Na; Ding, Yue; Chan, Leung Ting; Wang, Xu; Gao, Xin; Jiang, Songshan

    2016-01-01

    Abstract Neuronal mammalian target of rapamycin (mTOR) activity is a critical determinant of the intrinsic regenerative ability of mature neurons in the adult central nervous system (CNS). However, whether its action also applies to peripheral nervous system (PNS) neurons after injury remains elusive. To address this issue unambiguously, we used genetic approaches to determine the role of mTOR signaling in sensory axon regeneration in mice. We showed that deleting mTOR in dorsal root ganglion (DRG) neurons suppressed the axon regeneration induced by conditioning lesions. To establish whether the impact of mTOR on axon regeneration results from functions of mTOR complex 1 (mTORC1) or 2 (mTORC2), two distinct kinase complexes, we ablated either Raptor or Rictor in DRG neurons. We found that suppressing mTORC1 signaling dramatically decreased the conditioning lesion effect. In addition, an injury to the peripheral branch boosts mTOR activity in DRG neurons that cannot be completely inhibited by rapamycin, a widely used mTOR-specific inhibitor. Unexpectedly, examining several conditioning lesion–induced pro-regenerative pathways revealed that Raptor deletion but not rapamycin suppressed Stat3 activity in neurons. Therefore, our results demonstrate that crosstalk between mTOR and Stat3 signaling mediates the conditioning lesion effect and provide genetic evidence that rapamycin-resistant mTOR activity contributes to the intrinsic axon growth capacity in adult sensory neurons after injury. PMID:28101526

  19. Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe Consortium.

    PubMed

    Alafuzoff, Irina; Pikkarainen, Maria; Al-Sarraj, Safa; Arzberger, Thomas; Bell, Jeanne; Bodi, Istvan; Bogdanovic, Nenad; Budka, Herbert; Bugiani, Orso; Ferrer, Isidro; Gelpi, Ellen; Giaccone, Giorgio; Graeber, Manuel B; Hauw, Jean-Jacques; Kamphorst, Wouter; King, Andrew; Kopp, Nicolas; Korkolopoulou, Penelope; Kovács, Gábor G; Meyronet, David; Parchi, Piero; Patsouris, Efstratios; Preusser, Matthias; Ravid, Rivka; Roggendorf, Wolfgang; Seilhean, Danielle; Streichenberger, Nathalie; Thal, Dietmar R; Kretzschmar, Hans

    2006-08-01

    This interlaboratory study evaluated the reproducibility of the assessments of neuritic plaques and neurofibrillary tangles (NFTs)--the hallmark lesions of Alzheimer disease--and compared the staining between the BrainNet Europe centers. To reduce the topography-related inconsistencies in assessments, we used a 2-mm tissue microarray (TMA) technique. The TMA block included 42 core samples taken from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas silver stains using an immunohistochemical (IHC) method with antibodies directed to beta-amyloid (IHC/Abeta) and hyperphosphorylated tau (IHC/HPtau). The staining quality and the assessments differed between the participants, being most diverse with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas (good/acceptable stain in 57%) and IHC/Abeta (good/acceptable stain in 71%). The most uniform staining quality and assessment was obtained with the IHC/HPtau method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute) that was used significantly influenced the agreement, being highest with NIA-Reagan (54%) recommendations. This agreement was improved by visualization of NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to visualize NFTs and neuropil threads should be considered as a method of choice in a future diagnostic protocol for Alzheimer disease.

  20. Genomic variability of Pantoea ananatis in maize white spot lesions assessed by AFLP markers.

    PubMed

    Miller, A M; Figueiredo, J E F; Chaves, C L; Ruas, E A; Balbi-Peña, M I; Colauto, N B; Paccola-Meirelles, L D

    2016-12-19

    Measures to control maize white spot (MWS) caused by Pantoea ananatis are preferentially based on resistant cultivars. A lack of knowledge on the genetic variability of pathogens could interfere with the development and utilization of controlling strategies in this pathosystem. The main goals of this study were to investigate the genetic variability of 90 P. ananatis isolates from three different eco-geographical regions of Brazil by amplified fragment length polymorphism (AFLP), and to determine the presence of a universal P. ananatis plasmid in isolates from tropical Brazil. Analysis of genetic similarity by AFLP allowed us to categorize the 90 isolates into two groups. However, no correlation between the collecting sites and genetic groupings was observed. The polymorphism percentage found in P. ananatis ranged between 24.64 and 92.46%, and genetic diversity was calculated to be 0.07-0.09. The analysis of molecular variance showed that 99.18% of genetic variability was within the populations, providing evidence that evolutionary forces were acting on these populations. All P. ananatis isolates showed the P. ananatis universal plasmid (280 or 352 kb). This is the first report on the presence of a universal P. ananatis plasmid from MWS lesions in the tropical area.

  1. Assessment of different excitation wavelengths for photodetecting neoplastic urothelial lesions by laser-induced autofluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Anidjar, Maurice; Cussenot, Oliver; Avrillier, Sigrid; Ettori, Dominique; Teillac, Pierre; Le Duc, Alain

    1996-04-01

    We have designed a program using laser induced autofluorescence spectroscopy as a possible way to characterize urothelial tumors of the bladder. The autofluorescence spectra were compared between normal, suspicious and tumor areas of human bladder. Three different pulsed laser wavelengths were used for excitation: 308 nm (excimer), 337 nm (nitrogen) and 480 nm (dye laser). Excitation light was delivered by a specially devised multifiber catheter introduced through the working channel of a regular cystoscope under saline irrigation. The fluorescence light was focused into an optical multichannel analyzer detection system. The data was evaluated in 25 patients immediately before resection of a bladder tumor. Spectroscopic results were compared with histopathology. Upon 337 nm and 480 nm excitations, the overall intensity of the fluorescence spectra from bladder tumors was clearly reduced in comparison with normal urothelium, regardless of the stage and the grade of the tumor. upon 308 nm excitation, the shape of tumor fluorescence spectra, including carcinoma in situ, differed drastically from that of normal tissue. In this case, no absolute intensity measurements are needed and clear diagnosis can be achieved from fluorescence intensity ratio (360/440 nm). This spectroscopic study could be particularly useful for the design of a simplified autofluorescence imaging device for real-time routine detection of occult urothelial neoplastic lesions.

  2. [Assessment of amylase and lipase levels following puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions].

    PubMed

    Membrillo-Romero, Alejandro; Gonzalez-Lanzagorta, Rubén; Rascón-Martínez, Dulce María

    2016-12-14

    Puncture biopsy and fine needle aspiration guided by endoscopic ultrasound has been used as an effective technique and is quickly becoming the procedure of choice for diagnosis and staging in patients suspected of having pancreatic cancer. This procedure has replaced retrograde cholangiopancreatography and brush cytology due to its higher sensitivity for diagnosis, and lower risk of complications. To assess the levels of pancreatic enzymes amylase and lipase, after the puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions and the frequency of post-puncture acute pancreatitis. A longitudinal and descriptive study of consecutive cases was performed on outpatients submitted to puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions. Levels of pancreatic enzymes such as amylase and lipase were measured before and after the pancreatic puncture. Finally we documented post-puncture pancreatitis cases. A total of 100 patients who had been diagnosed with solid and cystic lesions were included in the study. Significant elevation was found at twice the reference value for lipase in 5 cases (5%) and for amylase in 2 cases (2%), none had clinical symptoms of acute pancreatitis. Eight (8%) of patients presented with mild nonspecific pain with no enzyme elevation compatible with pancreatitis. Pancreatic biopsy needle aspiration guided by endoscopic ultrasound was associated with a low rate of elevated pancreatic enzymes and there were no cases of post-puncture pancreatitis. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  3. [Assessment and correction of psychophysiological features in adolescents at the information science lesions].

    PubMed

    Shentsov, A A; Markina, L D

    2008-01-01

    The adaptation of teenagers to an educational process in a computer class with the optimum hygienic parameters was studied. The modified procedure "Examinees' emotional assessment of musical tracks" was established to efficiently prevent autonomic dysfunctions and emotional disorders.

  4. Activity Summaries as a Classroom Assessment Tool.

    ERIC Educational Resources Information Center

    McGee, Steven; Kirby, Jennifer; Croft, Steven K.

    This study explored the usefulness of a classroom assessment technique called the activity summary template. It is proposed that the activity summary template enables students to process and organize information learning during an investigation. This process will in turn help students to achieve greater learning outcomes. The activity summary…

  5. Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

    PubMed

    Wing, Ana Cristina; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Sacramento, Priscila M; Andrade, Regis M; Camargo, Solange; Rueda, Fernanda; Alves-Leon, Soniza V; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-02-01

    Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis. © 2015 John Wiley & Sons Ltd.

  6. Comparison Between Biofilm Production, Phospholipase and Haemolytic Activity of Different Species of Candida Isolated from Dental Caries Lesions in Children

    PubMed Central

    Shenoy, Neetha

    2016-01-01

    Introduction C.albicans is the most commonly isolated fungal pathogen in the oral cavity, but isolation of non-albicans Candida is increasing in recent years. We wish to demonstrate the virulence factors of Candida spp. isolated from the dental caries lesion of the children as presence of virulence factors determines the pathogenic potential of any microorganism. Aim To compare biofilm production, phospholipase and haemolytic activity of C.albicans with that of non-albicans species of Candida isolated from dental caries lesions of children to evaluate the role of non- albicans species of Candida in formation of dental caries. Materials and Methods Oral swabs were collected from caries lesion of 100 school children of age 5-10 years with dental caries. Candida isolates were tested for biofilm production, phospholipase and haemolytic activity. Statistical analysis was done by Chi-Square test and Mann-Whitney U test wherever applicable using SPSS version 11.5. Results Out of the 100 children with dental caries 37 were positive for Candida by smear or culture and 31 by culture. C.albicans was the most prevalent isolate followed by C.krusei, C.tropicalis and C.albicans. Out of 21 C.albicans isolates, 10 (47.6%) showed phospholipase activity and 18 (85.71%) produced biofilm. Of the 10 non-albicans strains, 5 (50%) showed phospholipase activity and 6 (60%) produced biofilm. All isolates of Candida produced haemolysin (100%). Conclusion There was no statistically relevant difference between the virulence factor production by C.albicans and non-albicans species of Candida. In other words, our study shows that both C.albicans and non-albicans species of Candida isolated from caries lesions of the children, produce these virulence factors. So we can say that non-albicans species of Candida also are involved in caries formation. PMID:27190803

  7. Standardized added metabolic activity (SAM): a partial volume independent marker of total lesion glycolysis in liver metastases.

    PubMed

    Mertens, Jeroen; Dobbeleir, André; Ham, Hamphrey; D'Asseler, Yves; Goethals, Ingeborg; Van de Wiele, Christophe

    2012-09-01

    The standardized added metabolic activity (SAM) is a new marker of total lesion glycolysis that avoids partial volume effect (PVE) and thresholding. SAM is calculated by drawing a volume of interest (VOI(1)) around the tumour and a larger VOI (VOI(2)) around VOI(1). Subtracting the background activity in VOI(2)-VOI(1) from VOI(1) yields SAM. If VOI(1) is set at a reasonable distance from the tumour, PVE are avoided. Phantom and initial clinical validation data are presented. Spheres of a Jaszczak phantom were filled with a 5.4, 3.64 and 2.0 times higher concentration relative to background activity and positron emission tomography (PET) data were acquired during 10 min. SAM of all spheres was expressed as a percentage of the expected value (the actual activity ratio minus 1). In 15 patients a 10-min list-mode acquisition PET study centred on their primary squamous cell carcinoma (PSCC) was performed and images of 1-10 min reconstructed. SAM1-9min values of PSCC were expressed as a percentage of SAM10min. Nineteen patients suffering from liver metastases treated with chemotherapy underwent PET/CT prior to (scan 1) and after 3-6 cycles of chemotherapy (scan 2). SAM and maximum standardized uptake values (SUV(max)) of the liver lesions on scan 1 (SAM1 and SUV(max)1) and the percentage reduction between both ΔSAM and ΔSUV(max) were related to Response Evaluation Criteria in Solid Tumors (RECIST) response. For the phantom acquisitions, the mean normalized SAM/sphere volume calculated was 94.9 % (SD 5.9 %) of the expected value. In the PSCC patients, the mean difference between SAM1min and SAM10min was only 4 % (SD 5 %). SUV(max)1min and SUV(max)10min proved to be not significantly different, but the variability was slightly larger than that of SAM (SD 6.4 %). SAM1 and ΔSAM values for responders versus non-responders were, respectively, 57 (SD 119) versus 297 (SD 625) for SAM1 (p = 0.2) and 99 % (SD 3 %) versus 32 % (SD 44 %) for ΔSAM (p = 0.001). SUV(max)1 and

  8. Assessment of enamel-dentin caries lesions detection using bitewing PSP digital images

    PubMed Central

    TORRES, Marianna Guanaes Gomes; SANTOS, Aline da Silva; NEVES, Frederico Sampaio; ARRIAGA, Marcel Lautenschlager; CAMPOS, Paulo Sérgio Flores; CRUSOÉ-REBELLO, Iêda

    2011-01-01

    Objectives The aim of this study was to evaluate the detection of enamel-dentin occlusal caries using photostimulable phosphor plates. Material and Methods The ability to detect enamel-dentin occlusal caries in 607 premolars and molars from 47 patients between 10 and 18 years old, referred to the School of Dentistry of the Federal University of Bahia, Brazil, was evaluated based on clinical and radiographic examinations, using the criteria proposed in a previous study. A total of 156 bitewing digital images were obtained using Digora® (Soredex Medical Systems, Helsinki, Finland) phosphor plates. The plates were scanned and the images were captured and displayed on a computer screen. Image evaluation was done using Digora® for Windows 2.1 software, Soredex®. The radiologists were allowed to use enhancement tools to obtain better visibility during scoring of the teeth based on the radiographic criteria proposed in a previous study. Descriptive analysis and chi-squared proportion tests were done at 5% significance level. Results The results of clinical examination showed a higher prevalence of teeth with a straight dark line or demineralization of the occlusal fissure (score 1) and a lower prevalence of sealed teeth (score 5). In the bitewing digital images, 47 teeth presented visible radiolucency, circumscribed, in dentin under occlusal enamel (enamel-dentin caries lesions). Conclusions Correlating the clinical and radiographic findings, it was found that in the majority of teeth diagnosed by radiographic images as having enamel-dentin caries, no caries could be detected by clinical examination. PMID:21986650

  9. Immunohistochemical assessment of mitochondrial superoxide dismutase (MnSOD) in colorectal premalignant and malignant lesions

    PubMed Central

    Piecuch, Adam; Dziewit, Bartosz; Segiet, Oliwia; Kurek, Józef; Kowalczyk-Ziomek, Grażyna; Wojnicz, Romuald; Helewski, Krzysztof

    2016-01-01

    Introduction It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues. Aim To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions. Material and methods This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica). Results Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma. Conclusions Development

  10. Population Based Assessment of MHC Class I Antigens Down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from Benign Breast Lesions

    DTIC Science & Technology

    2007-01-01

    Class I Antigens down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from Benign Breast Lesions...Based Assessment of MHC Class I Antigens down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from 5b...subsequent development of breast cancer from precancerous lesions, and as prognostic markers for progression from primary to metastatic disease. The major

  11. Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells.

    PubMed

    Meng, Yujiao; Wang, Mingxing; Xie, Xiangjiang; Di, Tingting; Zhao, Jingxia; Lin, Yan; Xu, Xiaolong; Li, Ningfei; Zhai, Yating; Wang, Yan; Li, Ping

    2017-05-01

    Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll‑like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848. Mice were intragastrically administered 100 mg/kg (high), 50 mg/kg (medium) and 25 mg/kg (low) paeonol, respectively. We evaluated inflammation of psori-asis‑like lesions based on histological changes, protein levels of myeloid differentiation factor 88 (MyD88) and TLR8 in skin lesions by western blotting, and levels of CD11c+ DCs in skin by immunoassay and in spleens by flow cytometry. Inflammatory cytokines [interleukin (IL)-23, IL-12 and IL-1β] in skin lesions and BMDCs were also assessed by RT-PCR and ELISA. Application of paeonol decreased IMQ-induced keratinocyte proliferation, and infiltration of CD3+ cells, while the treatment ameliorated CD11c+ cells in the spleen and skin, and reduced MyD88 and TLR8 proteins in skin lesions. Paeonol inhibited IMQ-induced mRNA expression of IL-23, but not IL-12 and IL-1β in BMDCs, along with significantly lower levels of DCs expressing MHCⅡ, CD80 and CD86 in vitro. These results indicate that paeonol suppresses the maturation and activation of DCs by decreasing MyD88 and TLR8 proteins in the TLR7/8 signaling pathway which finally alleviates psoriasis‑like skin lesions. The TLR7/8 signaling pathway in DCs provides an important insight into the mechanism of psoriasis, and paeonol may be a potent therapeutic drug for psoriasis.

  12. Motor dysfunction and alterations in glutathione concentration, cholinesterase activity, and BDNF expression in substantia nigra pars compacta in rats with pedunculopontine lesion.

    PubMed

    Blanco-Lezcano, Lisette; Jimenez-Martin, Javier; Díaz-Hung, Mei-Li; Alberti-Amador, Esteban; Wong-Guerra, Maylin; González-Fraguela, Ma Elena; Estupiñán-Díaz, Bárbara; Serrano-Sánchez, Teresa; Francis-Turner, Liliana; Delgado-Ocaña, Susana; Núñez-Figueredo, Yanier; Vega-Hurtado, Yamilé; Fernández-Jiménez, Isabel

    2017-04-21

    Pedunculopontine nucleus (PPN) has been considered a critically important region in the regulation of some of the physiological functions that fail during the progression of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN [through the injection of N-methyl-d-aspartate (NMDA) solution (concentration: 0.1M; volume: 0.5µL)] in motor execution and gait disorders and the changes in cellular and molecular indicators in rat nigral tissue were evaluated. The motor execution was assessed using the beam test (BT) and the gait disorders by footprint test. Glutathione (GSH) concentrations, acetyl cholinesterase enzymatic activity (AChE EA), and brain-derived neurotrophic factor (BDNF) mRNA expression in nigral tissue were analyzed. NMDA-lesioned rats showed fine motor dysfunction with a significant increase in the slow (p≤0.01) and fast movement (p≤0.01) time and in path deviation (p≤0.01) on the smaller diameter beams. Moreover, NMDA-lesioned rats exhibited an imprecise path with moments of advances and setbacks, alternating with left and right deviations, suspensions, and inverted positions. Footprint test revealed slight gait disorders, which were manifested by a reduction in the left and right stride lengths, the intra-step distance, and the support area (p≤0.01). Biochemical studies showed that 48h after the PPN neurotoxic injury, the GSH concentrations and BDNF expression were significantly increased (p≤0.01). These variables returned to normal values 7days after the PPN lesion; the AChE EA showed a significant increase at this time. These functional changes in nigral tissue could be a plastic responses associated with early PD.

  13. Influence of cerebral white matter lesions on the activities of daily living of older patients with mild stroke.

    PubMed

    Yamashita, Yutaka; Wada, Ikuo; Horiba, Mitsuya; Sahashi, Kento

    2016-08-01

    Neurological symptom severity is a prognostic factor for post-stroke activities of daily living (ADL). Recently, it has been reported that white matter lesions indicate poor functional prognosis in patients with stroke. The present study investigated the influence of white matter lesions on the ADL of older patients with stroke who have mild neurological symptoms. We investigated ADL at discharge in 44 patients with stroke (men, n = 27; women, n = 17; mean age 78 years [range 71-85 years]) aged ≥65 years with National Institutes of Health Stroke Scale scores of ≤5 (cerebral infarction, n = 37; cerebral hemorrhage, n = 7). We used single correlation analysis and multiple regression analysis to investigate factors that correlated with ADL at discharge. ADL at discharge was also evaluated on the basis of white matter lesion severity (Fazekas classification, grades 0-3). Single correlation analysis showed that age (r = -0.36, P = 0.016), male sex (r = 0.362, P = 0.016), neurological symptom severity (r = -0.361, P = 0.016), ADL on starting rehabilitation (r = 0.685, P < 0.001) and white matter lesion severity (r = -0.361, P = 0.016) significantly correlated with ADL at discharge. Multiple regression analysis showed that ADL on starting rehabilitation (β = 0.519, t = 4.723, P < 0.001) and white matter lesion severity (β = -0.309, t = -3.057, P < 0.01) were statistically significant prognostic factors for ADL at discharge. ADL at discharge score was significantly lower in the group with high white matter lesion severity (Fazekas, grade 2) than in the other two groups (Fazekas, grade 0, P < 0.01; Fazekas, grade 1, P < 0.05). Severe white matter lesions are a prognostic factor for poor ADL at discharge in older patients with stroke who have mild neurological symptoms. Geriatr Gerontol Int 2016; 16: 942-947. © 2015 Japan Geriatrics Society.

  14. Early increase in DcR2 expression and late activation of caspases in the platelet storage lesion.

    PubMed

    Plenchette, S; Moutet, M; Benguella, M; N'Gondara, J P; Guigner, F; Coffe, C; Corcos, L; Bettaieb, A; Solary, E

    2001-10-01

    Platelet transfusion is widely used to prevent bleeding in patients with severe thrombocytopenia. The maximal storage duration of platelet concentrates is usually 5 days, due to the platelet storage lesion that impairs their functions when stored for longer times. Some of the morphological and biochemical changes that characterize this storage lesion are reminiscent of cell death by apoptosis. The present study analyzed whether proteins involved in nucleated cell apoptosis could play a role in the platelet storage lesion. Storage of leukocyte-depleted platelets obtained by apheresis is associated with a late and limited activation of caspases, mainly caspase-3. This event correlates with an increased expression of the pro-apoptotic BH3-only protein Bim in the particulate fraction and a slight and late release of the pro-apoptotic mitochondrial protein Diablo/Smac in the cytosol. Platelets do not express the death receptors Fas, DR4 and DR5 on their plasma membrane, while the expression of the decoy receptor DcR2 increases progressively during platelet storage. Addition of low concentrations of the cryoprotector dimethylsulfoxide accelerates platelet caspase activation during storage, an effect that is partially prevented by the caspase inhibitor z-VAD-fmk. Altogether, DcR2 expression on the plasma membrane is an early event while caspase activation is a late event during platelet storage. These observations suggest that caspases are unlikely to account for the platelet storage lesion. As a consequence, addition of caspase inhibitors may not improve the quality of platelet concentrates stored in standard conditions.

  15. Assessment of coincidence and defect sizes in Bankart and Hill-Sachs lesions after anterior shoulder dislocation: a radiological study.

    PubMed

    Horst, K; Von Harten, R; Weber, C; Andruszkow, H; Pfeifer, R; Dienstknecht, T; Pape, H C

    2014-02-01

    Bankart and Hill-Sachs lesions are often associated with anterior shoulder dislocation. The MRI technique is sensitive in diagnosing both injuries. The aim of this study was to investigate Bankart and Hill-Sachs lesions with MRI to determine the correlation in occurrence and defect sizes of these lesions. Between 2006 and 2013, 446 patients were diagnosed with an anterior shoulder dislocation and 105 of these patients were eligible for inclusion in the study. All patients were examined using MRI. Bankart lesions were classified as cartilaginous or bony lesions. Hill-Sachs lesions were graded I-III using a modified Calandra classification. The co-occurrence of injuries was high [odds ratio (OR) = 11.47; 95% confidence interval (CI) = 3.60-36.52; p < 0.001]. Patients older than 29 years more often presented with a bilateral injury (OR = 16.29; 95% CI = 2.71-97.73; p = 0.002). A correlation between a Bankart lesion and the grade of a Hill-Sachs lesion was found (ρ = 0.34; 95% CI = 0.16-0.49; p < 0.001). Bankart lesions co-occurred more often with large Hill-Sachs lesions (O  = 1.24; 95% CI = 1.02-1.52; p = 0.033). If either lesion is diagnosed, the patient is 11 times more likely to have suffered the associated injury. The size of a Hill-Sachs lesion determines the co-occurrence of cartilaginous or bony Bankart lesions. Age plays a role in determining the type of Bankart lesion as well as the co-occurrence of Bankart and Hill-Sachs lesions. This study is the first to demonstrate the use of high-quality MRI in a reasonably large sample of patients, a positive correlation of Bankart and Hill-Sachs lesions in anterior shoulder dislocations and an association between the defect sizes.

  16. OCT assessment of non-cavitated occlusal carious lesions by variation of incidence angle of probe light and refractive index matching.

    PubMed

    Park, Kyung-Jin; Haak, Rainer; Ziebolz, Dirk; Krause, Felix; Schneider, Hartmut

    2017-07-01

    This study evaluated (1) the detection and assessment of non-cavitated occlusal carious lesions by spectral domain optical coherence tomography (SD-OCT) and (2) the impact of varying angle of incidence (AI) of probe light and refractive index matching (RIM). Nine extracted human molars with 18 occlusal lesions (ICDAS code 2) were visually selected. 18 regions of interest (ROI) were imaged with SD-OCT under varying AI (0°, ±5°, ±10°, ±15°) and with/without application of glycerine at 0°. X-ray micro computed tomography (μCT) was used as a validation standard. μCT and OCT signals were categorized according to the lesion extent: 1-sound, 2-lesion limited to half of enamel, 3-lesion limited to enamel, 4-lesion into dentin. Agreement between both methods was assessed. Intra- and inter-examiner reproducibility analyses were conducted. Cohen's kappa coefficient (κ), Spearman's rho correlation (rs) and Wilcoxon test (α=0.05). Slight to moderate agreement (κ=0.153) between μCT and OCT was obtained at an AI of 0° (Wilcoxon: p=0.02). With variation of Al a substantial agreement (κ=0.607) was observed (p=0.74). Spearman's correlation between both methods was 0.428 at 0°, 0.75 with varying AI and 0.573 with glycerine. Kappa values for intra-and inter-examiner analysis ranged between 0.81 and 0.88 and between 0.25 and 0.73, respectively. Variation of AI improves the detectability of non-cavitated occlusal carious lesions. RIM can enhance signal-to-noise ratio. OCT could provide additional diagnostic information in single and longitudinal assessments of occlusal carious lesions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 3-D Electrochemical Impedance Spectroscopy Mapping of Arteries to Detect Metabolically Active but Angiographically Invisible Atherosclerotic Lesions

    PubMed Central

    Packard, René R. Sevag; Luo, Yuan; Abiri, Parinaz; Jen, Nelson; Aksoy, Olcay; Suh, William M.; Tai, Yu-Chong; Hsiai, Tzung K.

    2017-01-01

    We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes. PMID:28744325

  18. Pre- and postsurgical biomagnetic activity in malt-type gastric lesions. A case report.

    PubMed

    Simopoulos, C; Anninos, P; Polychronidis, A; Kotini, A; Adamopoulos, A; Tamiolakis, D

    2003-03-01

    To evaluate the biomagnetic activity of a low-grade mucosa-associated lymphoid tissue (MALT-) type gastric lymphoma, and to determine if this procedure could be an adjunct to endoscopic ultrasonography (EUS) in the assessment of the disease pre- and postsurgically. A 47-year-old female with a 2-year clinical history of a low-grade MALT-type gastric lymphoma associated with Helicobacter pylori was examined. The disease showed no histologic remission after eradication of the H. pylori infection and subsequent treatment with chemotherapy and the patient was classified as stage II EA. A decision for surgical resection was made. Biomagnetic waveform recordings were made in the target area before and after surgery and the Fourier analysis of these recordings was performed. The gastric lymphoma biomagnetic waveforms showed high amplitudes (1.8 pT) before and low amplitudes (0.6 pT) after resection. The corresponding Fourier analysis demonstrated that the maximum spectral power of the presurgical measurement was elevated (mean 235 +/- 847 pT2/Hz) compared with that obtained postsurgically (mean 725 +/- 89 pT2/Hz). The difference was of statistical significance ( p < 0.0001, t-test). Biomagnetic monitoring of gastric lymphoma, which is an entirely new diagnostic modality, could be a supplement to EUS for assessing remission or persistence of disease with medical treatment during follow up.

  19. A two-dimensional locally regularized strain estimation technique: preliminary clinical results for the assessment of benign and malignant breast lesions

    NASA Astrophysics Data System (ADS)

    Brusseau, Elisabeth; Detti, Valérie; Coulon, Agnès; Maissiat, Emmanuèle; Boublay, Nawèle; Berthezène, Yves; Fromageau, Jérémie; Bush, Nigel; Bamber, Jeffrey

    2011-03-01

    We previously developed a 2D locally regularized strain estimation technique that was already validated with ex vivo tissues. In this study, our technique is assessed with in vivo data, by examining breast abnormalities in clinical conditions. Method reliability is analyzed as well as tissue strain fields according to the benign or malignant character of the lesion. Ultrasound RF data were acquired in two centers on ten lesions, five being classified as fibroadenomas, the other five being classified as malignant tumors, mainly ductal carcinomas from grades I to III. The estimation procedure we developed involves maximizing a similarity criterion (the normalized correlation coefficient or NCC) between pre- and post-compression images, the deformation effects being considered. The probability of correct strain estimation is higher if this coefficient is closer to 1. Results demonstrated the ability of our technique to provide good-quality strain images with clinical data. For all lesions, movies of tissue strain during compression were obtained, with strains that can reach 15%. The NCC averaged over each movie was computed, leading for the ten cases to a mean value of 0.93, a minimum value of 0.87 and a maximum value of 0.98. These high NCC values confirm the reliability of the strain estimation. Moreover, lesions were clearly identified for the ten cases investigated. Finally, we have observed with malignant lesions that compared to ultrasound data, strain images can put in relief a more important lesion size, and can help in evaluating the lesion invasive character.

  20. Improving CCTA-based lesions' hemodynamic significance assessment by accounting for partial volume modeling in automatic coronary lumen segmentation.

    PubMed

    Freiman, Moti; Nickisch, Hannes; Prevrhal, Sven; Schmitt, Holger; Vembar, Mani; Maurovich-Horvat, Pál; Donnelly, Patrick; Goshen, Liran

    2017-03-01

    The goal of this study was to assess the potential added benefit of accounting for partial volume effects (PVE) in an automatic coronary lumen segmentation algorithm that is used to determine the hemodynamic significance of a coronary artery stenosis from coronary computed tomography angiography (CCTA). Two sets of data were used in our work: (a) multivendor CCTA datasets of 18 subjects from the MICCAI 2012 challenge with automatically generated centerlines and 3 reference segmentations of 78 coronary segments and (b) additional CCTA datasets of 97 subjects with 132 coronary lesions that had invasive reference standard FFR measurements. We extracted the coronary artery centerlines for the 97 datasets by an automated software program followed by manual correction if required. An automatic machine-learning-based algorithm segmented the coronary tree with and without accounting for the PVE. We obtained CCTA-based FFR measurements using a flow simulation in the coronary trees that were generated by the automatic algorithm with and without accounting for PVE. We assessed the potential added value of PVE integration as a part of the automatic coronary lumen segmentation algorithm by means of segmentation accuracy using the MICCAI 2012 challenge framework and by means of flow simulation overall accuracy, sensitivity, specificity, negative and positive predictive values, and the receiver operated characteristic (ROC) area under the curve. We also evaluated the potential benefit of accounting for PVE in automatic segmentation for flow simulation for lesions that were diagnosed as obstructive based on CCTA which could have indicated a need for an invasive exam and revascularization. Our segmentation algorithm improves the maximal surface distance error by ~39% compared to previously published method on the 18 datasets from the MICCAI 2012 challenge with comparable Dice and mean surface distance. Results with and without accounting for PVE were comparable. In contrast

  1. Nandrolone decanoate and resistance exercise training favor the occurrence of lesions and activate the inflammatory response in the ventral prostate.

    PubMed

    Gomes, F C; Chuffa, L G A; Scarano, W R; Pinheiro, P F F; Fávaro, W J; Domeniconi, R F

    2016-05-01

    Age is a key factor in the development of prostatic lesions. An increase in reactive oxygen species levels occurs during aging. Furthermore, the indiscriminate use of anabolic androgenic steroids and physical exercise alter the availability of hormones and may promote the appearance of lesions. This study examined whether the use of nandrolone decanoate (ND), associated or not with resistance exercise training, affects the pathways related to the inflammatory response in the ventral prostate of adult and aged rats. Sprague-Dawley rats were distributed into eight experimental groups: sedentary with ND, sedentary without ND, exercise with ND, and exercise without ND. The animals performed resistance exercise training and received ND two times/week (5 mg/kg, i.m.) for 8 weeks. Adult rats were killed immediately following treatment completion, and aged rats remained untreated until reaching 300 days of age. The adult animals that received ND and performed resistance exercise training showed a higher occurrence of lesions with TLR4 activation. Marked IL-6 expression occurred in the group that performed resistance exercise training. The group exposed to ND showed overexpression of TLR2, TLR4, NOX1, Nrf2, TNF-α, and P38MAPK. The animals that received ND and performed training showed increase levels of NFκB, IRF3, IL-6, TNF-α, and NOX1. TLR2 and TLR4 showed no upregulation in the aged animals. The groups exercise + ND showed lesions in the adult stage and after aging, followed by molecular alterations. We concluded that nandrolone decanoate and resistance exercise training can promote the onset of prostatic tumors in the adult stage, and during aging, activating pathways involved in the inflammatory response.

  2. Can dual-energy computed tomography improve visualization of hypoenhancing liver lesions in portal venous phase? Assessment of advanced image-based virtual monoenergetic images.

    PubMed

    Caruso, Damiano; De Cecco, Carlo N; Schoepf, U Joseph; Schaefer, Amanda R; Leland, Parker W; Johnson, Dustin; Laghi, Andrea; Hardie, Andrew D

    The purpose was to assess image quality of portal-venous phase dual-energy computed tomography (DECT) for liver lesions. We performed 120-kVp-equivalent linear-blended (LB) and monoenergetic reconstructions from 40 to 190 keV by standard (VMI) and advanced virtual monoenergetic (VMI+) methods. Diagnostic performance, and quantitative and qualitative image analyses were assessed and compared. Liver contrast to noise ratio peaked at 40 keV_VMI+, while image quality and reader preference peaked at 50 keV_VMI+. 50 keV_VMI+ scored overall higher diagnostic performance: lesion sensitivity 95.4% vs. 83.3% for both 75 keV_VMI and LB. DECT improves assessment of hypoenhancing liver lesions on portal venous phase. 50 keV_VMI+ demonstrated the highest image quality and diagnostic performance over VMI and LB. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Assessing physical activity using wearable monitors: measures of physical activity.

    PubMed

    Butte, Nancy F; Ekelund, Ulf; Westerterp, Klaas R

    2012-01-01

    Physical activity may be defined broadly as "all bodily actions produced by the contraction of skeletal muscle that increase energy expenditure above basal level." Physical activity is a complex construct that can be classified into major categories qualitatively, quantitatively, or contextually. The quantitative assessment of physical activity using wearable monitors is grounded in the measurement of energy expenditure. Six main categories of wearable monitors are currently available to investigators: pedometers, load transducers/foot-contact monitors, accelerometers, HR monitors, combined accelerometer and HR monitors, and multiple sensor systems. Currently available monitors are capable of measuring total physical activity as well as components of physical activity that play important roles in human health. The selection of wearable monitors for measuring physical activity will depend on the physical activity component of interest, study objectives, characteristics of the target population, and study feasibility in terms of cost and logistics. Future development of sensors and analytical techniques for assessing physical activity should focus on the dynamic ranges of sensors, comparability for sensor output across manufacturers, and the application of advanced modeling techniques to predict energy expenditure and classify physical activities. New approaches for qualitatively classifying physical activity should be validated using direct observation or recording. New sensors and methods for quantitatively assessing physical activity should be validated in laboratory and free-living populations using criterion methods of calorimetry or doubly labeled water.

  4. Nondestructive assessment of the severity of occlusal caries lesions with near-infrared imaging at 1310 nm

    NASA Astrophysics Data System (ADS)

    Lee, Chulsung; Lee, Dustin; Darling, Cynthia L.; Fried, Daniel

    2010-07-01

    The high transparency of dental enamel in the near-infrared (NIR) at 1310 nm can be exploited for imaging dental caries without the use of ionizing radiation. The objective of this study is to determine whether the lesion contrast derived from NIR imaging in both transmission and reflectance can be used to estimate lesion severity. Two NIR imaging detector technologies are investigated: a new Ge-enhanced complementary metal-oxide-semiconductor (CMOS)-based NIR imaging camera, and an InGaAs focal plane array (FPA). Natural occlusal caries lesions are imaged with both cameras at 1310 nm, and the image contrast between sound and carious regions is calculated. After NIR imaging, teeth are sectioned and examined using polarized light microscopy (PLM) and transverse microradiography (TMR) to determine lesion severity. Lesions are then classified into four categories according to lesion severity. Lesion contrast increases significantly with lesion severity for both cameras (p<0.05). The Ge-enhanced CMOS camera equipped with the larger array and smaller pixels yields higher contrast values compared with the smaller InGaAs FPA (p<0.01). Results demonstrate that NIR lesion contrast can be used to estimate lesion severity.

  5. Nondestructive assessment of the severity of occlusal caries lesions with near-infrared imaging at 1310 nm

    PubMed Central

    Lee, Chulsung; Lee, Dustin; Darling, Cynthia L.; Fried, Daniel

    2010-01-01

    The high transparency of dental enamel in the near-infrared (NIR) at 1310 nm can be exploited for imaging dental caries without the use of ionizing radiation. The objective of this study is to determine whether the lesion contrast derived from NIR imaging in both transmission and reflectance can be used to estimate lesion severity. Two NIR imaging detector technologies are investigated: a new Ge-enhanced complementary metal-oxide-semiconductor (CMOS)-based NIR imaging camera, and an InGaAs focal plane array (FPA). Natural occlusal caries lesions are imaged with both cameras at 1310 nm, and the image contrast between sound and carious regions is calculated. After NIR imaging, teeth are sectioned and examined using polarized light microscopy (PLM) and transverse microradiography (TMR) to determine lesion severity. Lesions are then classified into four categories according to lesion severity. Lesion contrast increases significantly with lesion severity for both cameras (p<0.05). The Ge-enhanced CMOS camera equipped with the larger array and smaller pixels yields higher contrast values compared with the smaller InGaAs FPA (p<0.01). Results demonstrate that NIR lesion contrast can be used to estimate lesion severity. PMID:20799842

  6. Graft-induced Recovery of Inhibitory Avoidance Conditioning in Striatal Lesioned Rats is Related to Choline Acetyltransferase Activity

    PubMed Central

    Piña, Ana Luisa; Ormsby, Christopher Edward; Miranda, María Isabel; Jiménez, Nicolás; Tapia, Ricardo; Bermúdez-Rattoni, Federico

    1994-01-01

    Four groups of male Wistar rats showing disrupted inhibitory avoidance conditioning due to striatal lesions received either striatal or ventral mesencephalic brain grafts. Two additional non-lesioned groups were used as controls. Half of the groups was retrained in an inhibitory avoidance task at fifteen days postgraft and the other half at sixty days postgraft. Those animals receiving striatal grafts significantly improved their ability to acquire the inhibitory avoidance task at fifteen and sixty days postgraft, as opposed to those receiving mesencephalic grafts, which did not show behavioral recovery. Choline acetyltransferase and glutamate decarboxylase activities, as well as dopamine content, were measured in the grafted tissue. Striatal grafts showed levels of choline acetyltransferase activity similar to the control group. Moreover, a positive correlation was found between the choline acetyltransferase activity and the behavioral recovery. In contrast, both glutamate decarboxylase activity and dopamine levels were significantly lower in striatal and in mesencephalic grafts, as compared to the controls. These results show that striatal but not mesencephalic grafts can promote the restoration of the ability to acquire an inhibitory avoidance task even at early stages (15 days) of the development of the grafts. The results also suggest that acetylcholine plays an important role in behavioral recovery. PMID:7819369

  7. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status.

    PubMed

    Araujo-Pires, Ana Claudia; Francisconi, Carolina Favaro; Biguetti, Claudia Cristina; Cavalla, Franco; Aranha, Andreza Maria Fabio; Letra, Ariadne; Trombone, Ana Paula Favaro; Faveri, Marcelo; Silva, Renato Menezes; Garlet, Gustavo Pompermaier

    2014-01-01

    Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05). There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions, hierarchical cluster analysis

  8. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status

    PubMed Central

    ARAUJO-PIRES, Ana Claudia; FRANCISCONI, Carolina Favaro; BIGUETTI, Claudia Cristina; CAVALLA, Franco; ARANHA, Andreza Maria Fabio; LETRA, Ariadne; TROMBONE, Ana Paula Favaro; FAVERI, Marcelo; SILVA, Renato Menezes; GARLET, Gustavo Pompermaier

    2014-01-01

    Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. Methods The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. Results The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05). Conclusion There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions

  9. Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models.

    PubMed

    Boyle, Glen M; D'Souza, Marjorie M A; Pierce, Carly J; Adams, Ryan A; Cantor, Aaron S; Johns, Jenny P; Maslovskaya, Lidia; Gordon, Victoria A; Reddell, Paul W; Parsons, Peter G

    2014-01-01

    Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-βI, -βII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer.

  10. Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models

    PubMed Central

    Pierce, Carly J.; Adams, Ryan A.; Cantor, Aaron S.; Johns, Jenny P.; Maslovskaya, Lidia; Gordon, Victoria A.; Reddell, Paul W.; Parsons, Peter G.

    2014-01-01

    Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-βI, -βII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer. PMID:25272271

  11. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

    PubMed

    Cooke, Gillian E; Wetter, Nathan C; Banducci, Sarah E; Mackenzie, Michael J; Zuniga, Krystle E; Awick, Elizabeth A; Roberts, Sarah A; Sutton, Brad P; McAuley, Edward; Kramer, Arthur F

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

  12. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors

    PubMed Central

    Cooke, Gillian E.; Wetter, Nathan C.; Banducci, Sarah E.; Mackenzie, Michael J.; Zuniga, Krystle E.; Awick, Elizabeth A.; Roberts, Sarah A.; Sutton, Brad P.; McAuley, Edward; Kramer, Arthur F.

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment. PMID:26915025

  13. Macroscopic, microscopic, and chemical assessment of gunshot lesions on decomposed pig skin.

    PubMed

    Gibelli, Daniele; Brandone, Alberto; Andreola, Salvatore; Porta, Davide; Giudici, Elena; Grandi, Marco Aurelio; Cattaneo, Cristina

    2010-07-01

    Very little literature exists on gunshot wounds on decomposed material. In this study, seven pig heads underwent a shooting test. Entrance wounds from the first head underwent neutron activation analysis (NAA) and histological testing immediately after the firing test; the other six heads were exposed to two different environments (open air and soil) and analyzed by radiochemical and histological tests every 15 days. Gunshot wounds in air maintained their morphological characteristics, and those in soil showed severe alteration after 5 weeks. Microscopic testing verified positive results for lead in all gunshot wounds in open air, whereas in most of those in soil lead could not be detected. Radiochemical analysis performed by NAA yielded for all gunshot wounds but one antimony quantities in the range of 0.07-13.89 microg. In conclusion, it may be possible to detect residues of antimony even in degraded tissues.

  14. Assessment of regeneration in meniscal lesions by use of mesenchymal stem cells derived from equine bone marrow and adipose tissue.

    PubMed

    González-Fernández, Maria L; Pérez-Castrillo, Saúl; Sánchez-Lázaro, Jaime A; Prieto-Fernández, Julio G; López-González, Maria E; Lobato-Pérez, Sandra; Colaço, Bruno J; Olivera, Elías R; Villar-Suárez, Vega

    2016-07-01

    OBJECTIVE To assess the ability to regenerate an equine meniscus by use of a collagen repair patch (scaffold) seeded with mesenchymal stem cells (MSCs) derived from bone marrow (BM) or adipose tissue (AT). SAMPLE 6 female Hispano-Breton horses between 4 and 7 years of age; MSCs from BM and AT were obtained for the in vitro experiment, and the horses were subsequently used for the in vivo experiment. PROCEDURES Similarities and differences between MSCs derived from BM or AT were investigated in vitro by use of cell culture. In vivo assessment involved use of a meniscus defect and implantation on a scaffold. Horses were allocated into 2 groups. In one group, defects in the medial meniscus were treated with MSCs derived from BM, whereas in the other group, defects were treated with MSCs derived from AT. Defects were created in the contralateral stifle joint but were not treated (control samples). RESULTS Both types of MSCs had universal stem cell characteristics. For in vivo testing, at 12 months after treatment, treated defects were regenerated with fibrocartilaginous tissue, whereas untreated defects were partially repaired or not repaired. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSCs derived from AT could be a good alternative to MSCs derived from BM for use in regenerative treatments. Results also were promising for a stem cell-based implant for use in regeneration in meniscal lesions. IMPACT FOR HUMAN MEDICINE Because of similarities in joint disease between horses and humans, these results could have applications in humans.

  15. Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets

    PubMed Central

    Baimukanova, Gyulnar; Miyazawa, Byron; Potter, Daniel R.; Muench, Marcus O.; Bruhn, Roberta; Gibb, Stuart L.; Spinella, Philip C.; Cap, Andrew P.; Cohen, Mitchell J.; Pati, Shibani

    2016-01-01

    BACKGROUND In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. STUDY DESIGN AND METHODS In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. RESULTS Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A–induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A–challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs CONCLUSIONS In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to

  16. Combined blockade of angiotensin II type 1 receptor and activation of peroxisome proliferator-activated receptor-γ by telmisartan effectively inhibits vascularization and growth of murine endometriosis-like lesions.

    PubMed

    Nenicu, A; Körbel, C; Gu, Y; Menger, M D; Laschke, M W

    2014-05-01

    Is telmisartan effective in the treatment of endometriosis? Combined blockade of angiotensin II type 1 receptor (AT1R) and activation of peroxisome proliferator-activated receptor (PPAR)-γ by telmisartan inhibits vascularization and growth of murine endometriosis-like lesions. AT1R and PPAR-γ are involved in the regulation of inflammation, proliferation and angiogenesis. These processes are also crucial for the pathogenesis of endometriosis and both receptors are expressed in endometrial tissue. Telmisartan is a partial agonist of PPAR-γ, which additionally blocks AT1R. This was a randomized study in the mouse dorsal skinfold chamber and peritoneal model of endometriosis. Endometriosis-like lesions were induced in dorsal skinfold chambers of 21 female C57BL/6 mice, and in the peritoneal cavity of 15 additional animals, which were daily treated with an i.p. injection of pioglitazone (10 mg/kg, n = 12), telmisartan (10 mg/kg, n = 12) or vehicle (5% dimethyl sulfoxide (DMSO), n = 12) throughout an observation period of 14 and 28 days, respectively. The anti-angiogenic actions of pioglitazone, a full PPAR-γ agonist, and telmisartan were firstly assessed in vitro by an aortic ring assay. Endometriosis-like lesions were induced in the dorsal skinfold chamber or peritoneal cavity and the effects of telmisartan and pioglitazone on their vascularization, immune cell content and growth were studied by intravital fluorescence microscopy, high-resolution ultrasound imaging as well as histological, immunohistochemical and immunofluorescent analyses. Additional quantitative real-time polymerase chain reaction (qRT-PCR) arrays served for gene expression profiling of the lesions. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate vehicle-treated controls. Statistical significance was accepted for a value of P < 0.05. Telmisartan inhibited vascular sprout formation of aortic rings more effectively than

  17. Longitudinal assessment of cyst-like lesions of the knee and their relation to radiographic osteoarthritis and MRI-detected effusion and synovitis in patients with knee pain

    PubMed Central

    2010-01-01

    Introduction The purpose of the present study was to determine the prevalence of cystic lesions and cyst-like bursitides in subjects with frequent knee pain and to assess their relation to radiographic osteoarthritis (OA) severity; to describe bilaterality and size fluctuation of the lesions over 6 months; and to assess relations between the prevalence of synovium-lined lesions communicating with the joint capsule and severity of magnetic resonance imaging (MRI)-detected effusion and synovitis. Methods One hundred and sixty-three subjects (total 319 knees) aged 35 to 65 with chronic, frequent knee pain were included. Imaging with 3 Tesla MRI was performed at baseline and 6-month follow-up with the same protocols as those used in the Osteoarthritis Initiative. Severity of radiographic OA was assessed using the Kellgren-Lawrence grade (0 to 4). Severity of effusion and synovitis was graded 0 to 3 based on the Whole Organ Magnetic Resonance Imaging Score system. The associations of cysts and cyst-like bursitides and severity of radiographic OA, MRI-detected effusion and synovitis were analyzed using logistic regression controlling for clustering by person. The Wilcoxon signed-rank test was used to determine whether there was a significant change in the size of lesions between baseline and follow-up. Results At least one lesion (any type) was present in 222 (70%) knees. The most prevalent lesions were popliteal cysts (40%, 128/319), followed by subgastrocnemius bursitis (15%, 49/319) and proximal tibiofibular joint cysts (8%, 26/319). Bilateral lesions were seen in 49% of the subjects. Only popliteal cysts and subgastrocnemius bursitis showed a significant change in size (P < 0.001). No trend was observed between prevalence of any of the cyst-like lesions analyzed and the increasing radiographic OA severity. Increasing prevalence of subgastrocnemius bursitis was associated with increasing severity of effusion (P = 0.0072) and synovitis (P = 0.0033). Conclusions None of

  18. The peroxisome proliferator-activated receptor (PPAR) α agonist fenofibrate suppresses chemically induced lung alveolar proliferative lesions in male obese hyperlipidemic mice.

    PubMed

    Kuno, Toshiya; Hata, Kazuya; Takamatsu, Manabu; Hara, Akira; Hirose, Yoshinobu; Takahashi, Satoru; Imaida, Katsumi; Tanaka, Takuji

    2014-05-22

    Activation of peroxisome proliferator-activated receptor (PPAR) α disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARα agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously injected with 4-NQO to induce lung proliferative lesions, including adenocarcinomas. They were then fed a diet containing 0.01% or 0.05% fenofibrate for 29 weeks, starting 1 week after 4-NQO administration. At week 30, the incidence and multiplicity (number of lesions/mouse) of pulmonary proliferative lesions were lower in mice treated with 4-NQO and both doses of fenofibrate compared with those in mice treated with 4-NQO alone. The incidence and multiplicity of lesions were significantly lower in mice treated with 4-NQO and 0.05% fenofibrate compared with those in mice treated with 4-NQO alone (p<0.05). Both doses of fenofibrate significantly reduced the proliferative activity of the lesions in 4-NQO-treated mice (p<0.05). Fenofibrate also significantly reduced the serum insulin and insulin-like growth factor (IGF)-1 levels, and decreased the immunohistochemical expression of IGF-1 receptor (IGF-1R), phosphorylated Akt, and phosphorylated Erk1/2 in lung adenocarcinomas. Our results indicate that fenofibrate can prevent the development of 4-NQO-induced proliferative lesions in the lung by modulating the insulin-IGF axis.

  19. Assessment of coincidence and defect sizes in Bankart and Hill–Sachs lesions after anterior shoulder dislocation: a radiological study

    PubMed Central

    Von Harten, R; Weber, C; Andruszkow, H; Pfeifer, R; Dienstknecht, T; Pape, H C

    2014-01-01

    Objective: Bankart and Hill–Sachs lesions are often associated with anterior shoulder dislocation. The MRI technique is sensitive in diagnosing both injuries. The aim of this study was to investigate Bankart and Hill–Sachs lesions with MRI to determine the correlation in occurrence and defect sizes of these lesions. Methods: Between 2006 and 2013, 446 patients were diagnosed with an anterior shoulder dislocation and 105 of these patients were eligible for inclusion in the study. All patients were examined using MRI. Bankart lesions were classified as cartilaginous or bony lesions. Hill–Sachs lesions were graded I–III using a modified Calandra classification. Results: The co-occurrence of injuries was high [odds ratio (OR) = 11.47; 95% confidence interval (CI) = 3.60–36.52; p < 0.001]. Patients older than 29 years more often presented with a bilateral injury (OR = 16.29; 95% CI = 2.71–97.73; p = 0.002). A correlation between a Bankart lesion and the grade of a Hill–Sachs lesion was found (ρ = 0.34; 95% CI = 0.16–0.49; p < 0.001). Bankart lesions co-occurred more often with large Hill–Sachs lesions (OR = 1.24; 95% CI = 1.02–1.52; p = 0.033). Conclusion: If either lesion is diagnosed, the patient is 11 times more likely to have suffered the associated injury. The size of a Hill–Sachs lesion determines the co-occurrence of cartilaginous or bony Bankart lesions. Age plays a role in determining the type of Bankart lesion as well as the co-occurrence of Bankart and Hill–Sachs lesions. Advances in knowledge: This study is the first to demonstrate the use of high-quality MRI in a reasonably large sample of patients, a positive correlation of Bankart and Hill–Sachs lesions in anterior shoulder dislocations and an association between the defect sizes. PMID:24452107

  20. Spectral embedding based active contour (SEAC) for lesion segmentation on breast dynamic contrast enhanced magnetic resonance imaging

    PubMed Central

    Agner, Shannon C.; Xu, Jun; Madabhushi, Anant

    2013-01-01

    Purpose: Segmentation of breast lesions on dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) is the first step in lesion diagnosis in a computer-aided diagnosis framework. Because manual segmentation of such lesions is both time consuming and highly susceptible to human error and issues of reproducibility, an automated lesion segmentation method is highly desirable. Traditional automated image segmentation methods such as boundary-based active contour (AC) models require a strong gradient at the lesion boundary. Even when region-based terms are introduced to an AC model, grayscale image intensities often do not allow for clear definition of foreground and background region statistics. Thus, there is a need to find alternative image representations that might provide (1) strong gradients at the margin of the object of interest (OOI); and (2) larger separation between intensity distributions and region statistics for the foreground and background, which are necessary to halt evolution of the AC model upon reaching the border of the OOI. Methods: In this paper, the authors introduce a spectral embedding (SE) based AC (SEAC) for lesion segmentation on breast DCE-MRI. SE, a nonlinear dimensionality reduction scheme, is applied to the DCE time series in a voxelwise fashion to reduce several time point images to a single parametric image where every voxel is characterized by the three dominant eigenvectors. This parametric eigenvector image (PrEIm) representation allows for better capture of image region statistics and stronger gradients for use with a hybrid AC model, which is driven by both boundary and region information. They compare SEAC to ACs that employ fuzzy c-means (FCM) and principal component analysis (PCA) as alternative image representations. Segmentation performance was evaluated by boundary and region metrics as well as comparing lesion classification using morphological features from SEAC, PCA+AC, and FCM+AC. Results: On a cohort of 50

  1. Negative correlation between thyroperoxidase and dual oxidase H2O2-generating activities in thyroid nodular lesions.

    PubMed

    Ginabreda, Maria Gloria P; Cardoso, Luciene C; Nobrega, Flavia M; Ferreira, Andrea C F; Gonçalves, Manuel Domingos C; Vaisman, Mário; Carvalho, Denise P

    2008-02-01

    Iodine incorporation into thyroglobulin is dependent on the activities of both thyroperoxidase (TPO) and thyroid dual oxidase 2 (DuOx2). Although TPO expression is decreased in some thyroid nodular lesions, DuOx1 and 2 mRNA expressions are maintained, but DuOx H2O2-generating activity has never been evaluated in such tumors. Our goal was to determine DuOx activity in hypofunctioning lesions of the thyroid. We evaluated H2O2 generation by DuOx in 12 paranodular to cold nodule samples, 17 non-toxic multinodular goiters (MNG; 33 samples), 3 papillary carcinomas (PC; 4 samples), 3 follicular carcinomas (FC; 4 samples), and 10 follicular adenomas. DuOx activity was detected in all paranodular tissues (121+/-23 nmol H2O2/h per mg protein), but was undetectable (<1 nmol H2O2 generated) in all PC, two out of four FC samples and seven out of ten adenomas. In 11 MNG at least two different areas of the goiter have been evaluated, and in 5 of these goiters one of the samples had DuOx activity below the limit of detection. The coefficient of variation in MNG samples ranged from 11.3 to 57.2%. Interestingly, in all the adenomas studied, TPO activity (486+/-142 U/g protein, n=8) was well within the range found in paranodular tissues (414+/-116 U/g protein, n=3). We found a significant negative correlation between DuOx and TPO activities, suggesting that these enzymes are regulated in opposite directions, at least in thyroid tumors.

  2. Lesion of the Subfornical Organ attenuates Neuronal Activation of the Paraventricular Nucleus in response to Angiotensin II in normal rats.

    PubMed

    Meehan, Jessica; Collister, John P

    2011-09-23

    The subfornical organ, one of the central circumventricular organs, has been shown to mediate many of the effects of circulating angiotensin II (AngII). Where these signals are processed downstream is not fully understood. The SFO does indeed project to prominent cardiovascular regulatory centers such as the paraventricular nucleus (PVN), of whose neurons are activated by central AngII. We reasoned that AngII sensed at the SFO would cause neuronal activation at downstream hypothalamic areas such as the median preoptic nucleus and paraventricular nucleus, and as such would be diminished in animals with lesions of the SFO. To test this hypothesis, groups of rats underwent either SFO lesion (SFOx) or sham operation. Five days later rats were instrumented with radiotelemetry transducers for monitoring of mean arterial pressure (MAP) and venous catheters for infusions. MAP and heart rate were measured continuously. After a 4 day control period, infusion of AngII (0.575 µg/kg/min) was begun for a period of 2 hours. Rats were then sacrificed and brains were processed for neuronal Fos expression. AngII produced Fos expression in the SFO, MnPO and PVN of sham rats. Fos expression was greatly attenuated in the PVN of SFOx rats. These results support our hypothesis, suggesting that AngII sensitive neurons of the SFO can mediate neuronal activation in the PVN.

  3. Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the Nucleus Basalis Magnocellularis

    PubMed Central

    Sanchez-Alavez, Manuel; Ehlers, Cindy L.

    2015-01-01

    The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1K Hz tones and to release the lever upon hearing a 2 kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. PMID:25660307

  4. Physical activity assessment in children and adolescents.

    PubMed

    Sirard, J R; Pate, R R

    2001-01-01

    Chronic disease risk factors, including a sedentary lifestyle, may be present even in young children, suggesting that early prevention programmes may be critical to reducing the rates of chronic disease. Accurate assessment of physical activity in children is necessary to identify current levels of activity and to assess the effectiveness of intervention programmes designed to increase physical activity. This article summarises the strengths and limitations of the methods used to evaluate physical activity in children and adolescents. MEDLINE searches and journal article citations were used to locate 59 articles that validated physical activity measurement methods in children and adolescents. Only those methods that were validated against a more stringent measure were included in the review. Based on the definition of physical activity as any bodily movement resulting in energy expenditure (EE), direct observation of the individual's movement should be used as the gold standard for physical activity research. The doubly labelled water technique and indirect calorimetry can also be considered criterion measures for physical activity research, because they measure EE, a physiologic consequence closely associated with physical activity. Devices such as heart rate monitors, pedometers and accelerometers have become increasingly popular as measurement tools for physical activity. These devices reduce the subjectivity inherent in survey methods and can be used with large groups of individuals. Heart rate monitoring is sufficiently valid to use in creating broad physical activity categories (e.g. highly active, somewhat active, sedentary) but lacks the specificity needed to estimate physical activity in individuals. Laboratory and field validations of pedometers and accelerometers yield relatively high correlations using oxygen consumption (r = 0.62 to 0.93) or direct observation (r = 0.80 to 0.97) as criterion measures, although, they may not be able to capture all

  5. Assessment of BI-RADS category 4 lesions detected with screening mammography and screening US: utility of MR imaging.

    PubMed

    Strobel, Kevin; Schrading, Simone; Hansen, Nienke L; Barabasch, Alexandra; Kuhl, Christiane K

    2015-02-01

    To investigate the utility of magnetic resonance (MR) imaging according to different types of Breast Imaging Reporting and Data System (BI-RADS) category 4 findings from screening mammography and/or screening ultrasonography (US). This institutional review board-approved prospective study included 340 patients in whom 353 lesions were detected at screening mammography or US and were rated BI-RADS category 4 after appropriate conventional work-up. Written informed consent was obtained from all patients. Women underwent standard dynamic contrast material-enhanced MR imaging for further assessment. Women with negative or benign MR findings who did not proceed to biopsy underwent intensified follow-up for at least 18 months. Pure clustered microcalcifications were followed up for at least 24 months. Of the 353 study findings, 66 (18.7%) were finally shown to be true-positive (23 cases of ductal carcinoma in situ [DCIS], 43 invasive cancers) and 287 (81.3%) were false-positive. Assessment of MR imaging findings led to a correct diagnosis of no breast cancer in 264 of the 287 false-positive findings (92%) and helped confirm the presence of breast cancer in 63 of 66 malignancies. The false-negative rate for pure clustered microcalcifications was 12% (three of 25 cases) because of three nonenhancing low-grade DCIS cases; in turn, MR imaging depicted additional invasive cancers in three women with false-positive findings from mammography and US. For mammographic findings other than pure clustered microcalcifications, MR imaging increased the positive predictive value (PPV) from 17.5% (21 of 120 cases; 95% confidence interval [CI]: 10.7%, 24.3%) to 78% (21 of 27 cases; 95% CI: 62.1%, 93.5%), with a false-negative rate of 0%. For all US findings, MR imaging increased the PPV from 12.9% (20 of 155 cases; 95% CI: 7.6%, 18.2%) to 69% (20 of 29 cases; 95% CI: 52.2%, 85.8%), again with a false-negative rate of 0%. MR imaging resulted in false-positive findings that led to MR

  6. Oral lesions as clinical markers of highly active antiretroviral therapy failure: a nested case-control study in Mexico City.

    PubMed

    Ramírez-Amador, Velia; Ponce-de-León, Sergio; Anaya-Saavedra, Gabriela; Crabtree Ramírez, Brenda; Sierra-Madero, Juan

    2007-10-01

    Clinical markers that may predict virological failure during highly active antiretroviral therapy (HAART) have not been evaluated adequately. The aim of the present study was to evaluate the usefulness of human immunodeficiency virus (HIV)-related oral lesions as clinical predictors of virological failure in HIV-infected patients receiving HAART. A nested case-control study was conducted within a cohort of 1134 HIV-infected patients receiving HAART who attended the AIDS Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City during the period 1997-2005. Case patients were patients who, after achieving an undetectable viral load, had at least 1 viral load determination > or = 2000 copies/mL while receiving treatment. Control subjects were patients who, after achieving an undetectable viral load, continued to have undetectable viral loads during the follow-up period. There were 2-3 control subjects for each case patient, matched according to duration of follow-up. Oral examinations were blinded to viral loads and CD4+ lymphocyte counts. Analyses were performed with multivariate conditional logistic regression models, and associations were shown as odds ratios (ORs) with 95% confidence intervals (CI). Positive predictive values were calculated. The target cohort consisted of 431 HIV-infected individuals; 47 case patients and 132 control subjects underwent complete oral examinations and formed the basis of the analysis. At the visit at which an undetectable viral load was determined, case patients and control subjects showed a similar frequency of HIV-related oral lesions (21.3% vs. 17.4%) (OR, 1.39; 95% CI, 0.57-3.38; P=.47). At the visit at which virological failure was determined, case patients showed a higher risk for HIV-related oral lesions (OR, 14.5; 95% CI, 4.21-49.94; P<.001) and oral candidosis (OR, 26.2; 95% CI, 3.34-205.9; P<.001) than did control subjects. The positive predictive value of HIV-related oral lesions

  7. β-Defensin-2 Protein Is a Serum Biomarker for Disease Activity in Psoriasis and Reaches Biologically Relevant Concentrations in Lesional Skin

    PubMed Central

    Jansen, Patrick A. M.; Rodijk-Olthuis, Diana; Hollox, Edward J.; Kamsteeg, Marijke; Tjabringa, Geuranne S.; de Jongh, Gys J.; van Vlijmen-Willems, Ivonne M. J. J.; Bergboer, Judith G. M.; van Rossum, Michelle M.; de Jong, Elke M. G. J.; den Heijer, Martin; Evers, Andrea W. M.; Bergers, Mieke; Armour, John A. L.

    2009-01-01

    Background Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. Methodology/Principal Findings We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. Conclusions/Significance Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases. PMID:19266104

  8. Management guidelines for participation in collision activities with congenital, developmental, or post-injury lesions involving the cervical spine.

    PubMed

    Torg, J S; Ramsey-Emrhein, J A

    1997-01-01

    Conditions involving the cervical spine in the athlete requiring management decisions are numerous. The purpose of this paper is to present appropriate guidelines for return to collision activities in those with congenital, developmental, or post-injury lesions. Collision activities include boxing, football, ice hockey, lacrosse, rugby and wrestling. Information compiled from over 1200 cervical spine lesions documented by the National Football Head and Neck Injury Registry, an extensive literature review, as well as an understanding of injury mechanisms have resulted in reasonable management guidelines. Each of the congenital, developmental and post-traumatic conditions presented are identified as either no contraindication, relative contraindication, or an absolute contraindication on the basis of a variety of parameters. Conditions involved in the discussion include: odontoid anomalies, spina bifida occulta, atlanto-occipital fusion, K1ippel-Feil syndrome, cervical canal stenosis, spear tackler's spine; and traumatic conditions of the upper, middle and lower cervical spine including ligamentous injuries and fractures, intervertebral disc injuries and post-cervical spine fusion. It should be emphasized that the proposed guidelines should be used in the decision making process and in conjunction with other such factors as age, experience, ability of the individual, level of participation, position played, as well as the attitude and desires of the athlete and his parents, where applicable following an informed discussion of the problem with particular regard to potential risk.

  9. Aetiology of abfraction lesions.

    PubMed

    Lyons, K

    2001-09-01

    The aetiology of abfraction lesions is complex. Most evidence indicates that physical loading forces are a major contributing factor, although they are unlikely to be entirely responsible. Intraoral chemical influences and toothbrush abrasion, combined with the dynamics of inter-occlusal activity such as chewing, swallowing, and parafunction, lead to stress corrosion and may contribute to abfraction lesions. The multifactorial aetiology that operates in the initiation and progression of these lesions has made investigation difficult. Various theories have been proposed and numerous surveys and studies conducted, but the primary causal factor has yet to be definitively determined. This review concludes that occlusal loading is the initiating factor in the development of abfraction lesions.

  10. Depth and activity of carious lesions as indicators for the regenerative potential of dental pulp after intervention.

    PubMed

    Bjørndal, Lars; Demant, Sune; Dabelsteen, Sally

    2014-04-01

    Studies on dental regeneration involving interventions for pulp therapy such as regeneration and revascularization procedures are promising for the injured tooth; however, a complete replication of the original pulp tissue does not seem to take place. In cases in which we wish to preserve or maintain parts of the pulp during treatment, it is apparent that the effectiveness of healing or biological regeneration is dependent on the degree of inflammation of the pulp tissue. Thus, the control or prevention of a pulp infection is still a major issue for the clinicians. Data indicate that the typical reason for performing endodontic treatment is deep caries. The biological concept of vital pulp therapy associated with deep caries takes the treatment and evaluation of the unexposed as well as the exposed pulp into account. Interestingly, the clinical diagnosis is typically the same. Deep caries with reversible pulpitis may receive differing treatments such as excavation procedures aiming to avoid pulp exposure or more pulp invasive treatments such as pulp capping or pulpotomy. This should not be the case. Consequently, huge treatment variation is noted among clinicians based on the same caries diagnosis. Which treatment should be selected? High-quality trials are needed, and it is important to obtain information on the actual lesion depth and an estimate of the lesion activity before treatment. These may be basic indicators for the regenerative potential of dental pulp. Recent clinical trials dealing with the treatment of deep caries lesion are discussed, including pulp invasive and noninvasive concepts, to attempt to solve the task of getting the best clinical outcome for adult patients. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    PubMed

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all P<0.05). Multivariate analysis revealed that more MVPA was associated with less brain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.

  12. Effect of CPP-ACP Paste on Enamel Carious Lesion of Primary Upper Anterior Teeth Assessed by Quantitative Light-Induced Fluorescence: A One-Year Clinical Trial.

    PubMed

    Sitthisettapong, Thanya; Doi, Takashi; Nishida, Yuhei; Kambara, Masaki; Phantumvanit, Prathip

    2015-01-01

    The purpose of this clinical trial was to evaluate the effect of 1 year of daily application of 10% w/v CPP-ACP (casein phosphopeptide-amorphous calcium phosphate) paste in addition to regular toothbrushing with fluoridated toothpaste on the remineralization of enamel carious lesions in preschool children using quantitative light-induced fluorescence (QLF). A total of 103 Thai children (aged 2(1)/2-3(1)/2 years) with high caries risk who had at least 1 enamel carious lesion (ICDAS 1-3) on the labial surface of the upper anterior teeth were assigned to receive either CPP-ACP paste (n = 53) or placebo control (n = 50) following toothbrushing with fluoridated toothpaste after lunch at school. QLF measurement was performed at baseline, 6 months and 1 year. At 1 year, a significant reduction in fluorescence loss (ΔF), lesion area and lesion volume (ΔQ; p ≤ 0.001) of the lesions were found over time in both groups. However, no significant difference was observed between the groups (p = 0.79, 0.98 and 0.88, respectively). There was no statistically significant difference between the odds of ΔQ transition to a stage of regression or arrest compared with progression from baseline to 1 year between the two groups (OR = 1.03, 95% CI 0.31-3.39). The daily application of 10% w/v CPP-ACP paste on a school day for 1 year resulted in no improvement of enamel carious lesion remineralization in the primary upper anterior teeth as assessed by QLF. The lesion improvement was not superior to remineralization from regular toothbrushing with fluoridated toothpaste alone in these children. © 2015 S. Karger AG, Basel.

  13. Quantitative assessment of growth plate activity

    SciTech Connect

    Harcke, H.T.; Macy, N.J.; Mandell, G.A.; MacEwen, G.D.

    1984-01-01

    In the immature skeleton the physis or growth plate is the area of bone least able to withstand external forces and is therefore prone to trauma. Such trauma often leads to premature closure of the plate and results in limb shortening and/or angular deformity (varus or valgus). Active localization of bone seeking tracers in the physis makes bone scintigraphy an excellent method for assessing growth plate physiology. To be most effective, however, physeal activity should be quantified so that serial evaluations are accurate and comparable. The authors have developed a quantitative method for assessing physeal activity and have applied it ot the hip and knee. Using computer acquired pinhole images of the abnormal and contralateral normal joints, ten regions of interest are placed at key locations around each joint and comparative ratios are generated to form a growth plate profile. The ratios compare segmental physeal activity to total growth plate activity on both ipsilateral and contralateral sides and to adjacent bone. In 25 patients, ages 2 to 15 years, with angular deformities of the legs secondary to trauma, Blount's disease, and Perthes disease, this technique is able to differentiate abnormal segmental physeal activity. This is important since plate closure does not usually occur uniformly across the physis. The technique may permit the use of scintigraphy in the prediction of early closure through the quantitative analysis of serial studies.

  14. Different imaging methods in the comparative assessment of vascular lesions: color-coded duplex sonography, laser Doppler perfusion imaging, and infrared thermography

    NASA Astrophysics Data System (ADS)

    Urban, Peter; Philipp, Carsten M.; Weinberg, Lutz; Berlien, Hans-Peter

    1997-12-01

    Aim of the study was the comparative investigation of cutaneous and subcutaneous vascular lesions. By means of color coded duplex sonography (CCDS), laser doppler perfusion imaging (LDPI) and infrared thermography (IT) we examined hemangiomas, vascular malformations and portwine stains to get some evidence about depth, perfusion and vascularity. LDI is a helpful method to get an impression of the capillary part of vascular lesions and the course of superficial vessels. CCDS has disadvantages in the superficial perfusion's detection but connections to deeper vascularizations can be examined precisely, in some cases it is the only method for visualizing vascular malformations. IT gives additive hints on low blood flow areas or indicates arterial-venous-shunts. Only the combination of all imaging methods allows a complete assessment, not only for planning but also for controlling the laser treatment of vascular lesions.

  15. Expression of OASIS, a CREB/ATF family transcription factor, in CNS lesion and its transcriptional activity.

    PubMed

    Nikaido, Takuya; Iseki, Ken; Mori, Tetsuji; Takaki, Hiromi; Yokoya, Sachihiko; Hagino, Seita; Takeda, Junko; Zhang, Yuxiang; Takeuchi, Mayumi; Kikuchi, Shin-ichi; Wanaka, Akio

    2002-12-01

    We reported the expression patterns of a novel member of the CREB/ATF family, OASIS, in central nervous system (CNS) lesions and its transcriptional activity. OASIS gene expression was upregulated in the stab-injured spinal cord. Double labeling experiments revealed that the distribution of OASIS mRNA-positive cells overlapped with a population of GFAP-immunoreactive cells. This finding suggested that OASIS might regulate expression of important downstream molecules in certain subset of the reactive astrocytes (e.g. inhibitory substances in injured brain). In gel shift assays, OASIS was able to specifically bind to CRE as CREB family members were. We then examined transcriptional activity of full-length OASIS with GAL4-UAS-luciferase reporter assay in COS7 cells. OASIS protein activated transcription, but did not inhibit basal transcription driven by AdML promoter. To determine critical portion(s) of the OASIS protein in transcriptional activation, we examined the activity of various deletion constructs of OASIS gene. The assay revealed that a strong transcriptional activation domain lay in the N-terminal region where acidic amino acids clustered and a possible repression domain, which had not been reported for other CREB/ATF family members, lay in the more C-terminal region. We therefore proposed that OASIS protein positively regulated gene transcription in a subset of reactive astrocytes, and thereby influenced the reaction of injured CNS tissues.

  16. Evaluation of plasma muscle enzyme activity as an indicator of lesion characteristics and prognosis in horses undergoing celiotomy for acute gastrointestinal pain

    PubMed Central

    2014-01-01

    Background In horses undergoing celiotomy for acute gastrointestinal pain, identification of variables correlating with lesion severity and location, and survival provide veterinarians and owners with information that aids in making informed decisions regarding appropriate treatment. Muscle enzyme activity is often increased in horses undergoing celiotomy for acute gastrointestinal pain and it is not known if muscle enzyme activity increase is specific to lesion type or impacts prognosis for survival. The objective of this study was to evaluate the relationship of pre-operative increase in muscle enzyme activities with intestinal lesion characteristics, specifically lesion location (large versus small intestine) and whether it was strangulating versus nonstrangulating, and case survival in horses undergoing celiotomy for acute gastrointestinal pain. Methods Records of 241 horses undergoing exploratory laparotomy for colic were reviewed retrospectively. Evaluation of preoperative plasma aspartate aminotransferase (AST), creatine kinase (CK), sorbitol dehydrogenase (SDH), and gamma-glutamyltransferase (GGT) activities, fibrinogen and glucose concentrations, and hematocrit (HCT) and their association with gastrointestinal lesion characteristics and survival was performed. Results Pre-operative increase in plasma CK and AST activity, and HCT and decrease in plasma bilirubin concentration were significantly associated with presence of lesions resulting in intestinal ischemia. Increase in plasma CK activity and HCT were significantly associated with a decreased probability of survival to hospital discharge. Plasma GGT and SDH activity, and glucose and fibrinogen concentration were not significantly associated with survival or severity of disease in multivariate analysis. Conclusions Plasma muscle enyzme activity may be useful as a prognostic indicator in equine colic cases. Given that increases in plasma CK and AST activity were significantly associated with nonsurvival

  17. Environmental Impact Assessment and Space Activities

    NASA Astrophysics Data System (ADS)

    Viikari, L.

    Environmental Impact Assessment (EIA) is a common tool for environment a l protection and management on Earth today, as prior assessment of the environmental consequences of planned activities. It is meant to provide the decision-makers with as comprehensive as possible information about the different environmental effects the proposed activity would entail, including alternative courses of action and the zero-alternative (i.e. the no action alternative). Additionally, plans for mitigation in respect of each alternative are to be outlined. The assessments take account of i.a. environmental impacts on ecosystems, diminution of aesthetic and scientific values, long-term or cumulative effects, as well as transfrontier implications. They also consider issues such as pollution control, environmental protection measures, reporting, post-project analysis, rehabilitation and so on. Also uncertainties in the assessment process are to be expressly presented. Most importantly, a common requirement also is that the results of the impact studies are presented in a way comprehensible to the g neral public,e too. Although the central aspect of the EIA is to provide the decision-makers with scientific information, the process also has other important implications. One of the most relevant of them is the involvement of those people potentially affected in some way by the proposed activity: most EIA systems require in some way the participation of the public, alongside with the relevant governmental authorities and other stake-holders. Such public involvement has various aims and goals: it may serve as a testimony to good governance in general, or be considered in more practical terms as improved planning, due to the concrete contribution of the public to the decision-making process. Obviously, it also is a tool for reducing conflict and developing wider support for the eventual decisions. In short, it enables the public to gain information about planned activities and influence

  18. Clinical Significance of A Single Multi-Slice CT Assessment in Patients with Coronary Chronic Total Occlusion Lesions Prior to Revascularization

    PubMed Central

    Qu, Xinkai; Fang, Weiyi; Gong, Kaizheng; Ye, Jianding; Guan, Shaofeng; Li, Ruogu; Xu, Yingjia; Shen, Yan; Zhang, Min; Liu, Hua; Xie, Wenhui

    2014-01-01

    Accurate assessment of coronary chronic total occlusion (CTO) lesion is essential to design an appropriate procedural strategy before revascularization. The present study aims to evaluate the significance of a single multislice computed tomography (MSCT) examination in patients with CTO lesion. We retrospectively analyzed the clinical data of 23 CTO lesions in twenty patients underwent computed tomography coronary angiography (CTCA) and SPECT. The CTCA was more powerful and sensitive to determine the CTO lesion length (100% v.s 47.8%) and to identify the length and location of calcification in occluded vessels compared with the coronary angiography (CAG). The LVEF measured by MSCT was comparable to that from the gated SPECT. Myocardial perfusion imaging showed that the location of the early defect region identified by MSCT was corresponded to the nuclide filling defect on the stressed 201thallium-SPECT imaging. The late hyperenhancement on MSCT was presented as incomplete nuclide filling on the 99mTc-MIBI imaging. The results suggested that a single MSCT examination in previous myocardial infarction without revascularization facilitates to provide some valuable information on the nature of the occluded lesion, myocardial perfusion and globe cardiac function, which would be helpful to design appropriate revascularization strategy in these subjects. PMID:24905494

  19. Prospective application of pre-defined intravascular ultrasound criteria for assessment of intermediate left main coronary artery lesions results from the multicenter LITRO study.

    PubMed

    de la Torre Hernandez, Jose M; Hernández Hernandez, Felipe; Alfonso, Fernando; Rumoroso, Jose R; Lopez-Palop, Ramon; Sadaba, Mario; Carrillo, Pilar; Rondan, Juan; Lozano, Iñigo; Ruiz Nodar, Juan M; Baz, Jose A; Fernandez Nofrerias, Eduard; Pajin, Fernando; Garcia Camarero, Tamara; Gutierrez, Hipolito

    2011-07-19

    This study is a prospective validation of 6 mm(2) as a minimum lumen area (MLA) cutoff value for revascularization of left main coronary artery (LMCA) lesions. Lesions involving the LMCA are prognostically relevant. Angiography has important limitations in the evaluation of LMCA lesions with intermediate severity. An MLA of 6 mm(2) assessed by intravascular ultrasound has been proposed as a cutoff value to determine lesion severity, but there are no large studies evaluating the prospective application and safety of this approach. We have designed a multicenter, prospective study. Consecutive patients with intermediate lesions in unprotected LMCA were evaluated with intravascular ultrasound. An MLA <6 mm(2) was used as criterion for revascularization. A total of 354 patients were included in 22 centers. LMCA revascularization was performed in 90.5% (152 of 168) of patients with an MLA <6 mm(2) and was deferred in 96% (179 of 186) of patients with an MLA of 6 mm(2) or more. A large scatter was observed between both groups regarding angiographic parameters. In a 2-year follow-up period, cardiac death-free survival was 97.7% in the deferred group versus 94.5% in the revascularized group (p = 0.5), and event-free survival was 87.3% versus 80.6%, respectively (p = 0.3). In the 2-year period, only 8 (4.4%) patients in the deferred group required subsequent LMCA revascularization, none with an infarction. Angiographic measurements are not reliable in the assessment of intermediate LMCA lesions. An MLA of 6 mm(2) or more is a safe value for deferring revascularization of the LMCA, given the application of the clinical and angiographic inclusion criteria used in this study. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice.

    PubMed

    Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

    2017-01-01

    Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque.

  1. Topographical Organization of Mu and Beta Band Activity Associated with Hand and Foot Movements in Patients with Perirolandic Lesions

    PubMed Central

    Willemse, Ronald B; de Munck, Jan C; Verbunt, Jeroen P.A; van ’t Ent, Dennis; Ris, Peterjan; Baayen, Johannes C; Stam, Cornelis J; Vandertop, W. Peter

    2010-01-01

    To study the topographical organization of mu and beta band event-related desynchronization (ERD) associated with voluntary hand and foot movements, we used magnetoencephalographic (MEG) recordings from 19 patients with perirolandic lesions. Synthetic aperture magnetometry (SAM) was used to detect and localize changes in the mu (7 - 11 Hz) and beta (13 - 30 Hz) frequency bands associated with repetitive movements of the hand and foot and overlaid on individual coregistered magnetic resonance (MR) images. Hand movements showed homotopic and contralateral ERD at the sensorimotor (S/M) cortex in the majority of cases for mu and to a lesser extent for beta rhythms. Foot movements showed an increased heterotopic distribution with bilateral and ipsilateral ERD compared to hand movements. No systematic topographical segregation between mu and beta ERD could be observed. In patients with perirolandic lesions, the mu and beta band spatial characteristics associated with hand movements retain the expected functional-anatomical boundaries to a large extent. Foot movements have altered patterns of mu and beta band ERD, which may give more insight into the differential functional role of oscillatory activity in different voluntary movements. PMID:21347203

  2. Topographical organization of mu and Beta band activity associated with hand and foot movements in patients with perirolandic lesions.

    PubMed

    Willemse, Ronald B; de Munck, Jan C; Verbunt, Jeroen P A; van 't Ent, Dennis; Ris, Peterjan; Baayen, Johannes C; Stam, Cornelis J; Vandertop, W Peter

    2010-08-02

    To study the topographical organization of mu and beta band event-related desynchronization (ERD) associated with voluntary hand and foot movements, we used magnetoencephalographic (MEG) recordings from 19 patients with perirolandic lesions. Synthetic aperture magnetometry (SAM) was used to detect and localize changes in the mu (7 - 11 Hz) and beta (13 - 30 Hz) frequency bands associated with repetitive movements of the hand and foot and overlaid on individual coregistered magnetic resonance (MR) images. Hand movements showed homotopic and contralateral ERD at the sensorimotor (S/M) cortex in the majority of cases for mu and to a lesser extent for beta rhythms. Foot movements showed an increased heterotopic distribution with bilateral and ipsilateral ERD compared to hand movements. No systematic topographical segregation between mu and beta ERD could be observed. In patients with perirolandic lesions, the mu and beta band spatial characteristics associated with hand movements retain the expected functional-anatomical boundaries to a large extent. Foot movements have altered patterns of mu and beta band ERD, which may give more insight into the differential functional role of oscillatory activity in different voluntary movements.

  3. Alpha1-adrenoceptors mediate dihydroxyphenylalanine-induced activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaques.

    PubMed

    Visanji, N P; Fox, S H; Johnston, T H; Millan, M J; Brotchie, J M

    2009-01-01

    The mechanisms underlying actions of dihydroxyphenylalanine (L-DOPA) in Parkinson's disease remain to be fully elucidated. Noradrenaline formed from L-DOPA may stimulate alpha(1)-adrenoceptors. We assessed the involvement of alpha(1)-adrenoceptors in actions of L-DOPA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaques. In each animal, the minimal dose of L-DOPA required to alleviate parkinsonian symptoms was defined (12.5-25 mg/kg p.o.). The effects of coadministration of the alpha(1)-adrenoceptor antagonist prazosin ([4-(4-amino-6,7-dimethoxy-quinazolin-2-yl) piperazin-1-yl]-(2-furyl)methanone) on motor activity, parkinsonism, and dyskinesia were assessed. Antiparkinsonian benefit was accompanied by mild dyskinesia. L-DOPA also elicited hyperactivity, i.e., activity greater than that seen in normal animals. Coadministration of prazosin (0.16-0.63 mg/kg p.o.) with L-DOPA did not significantly affect either its antiparkinsonian actions or dyskinesia. However, prazosin significantly and dose-dependently attenuated L-DOPA-induced activity, reducing it to a level equivalent to that of normal animals. More specifically, during periods of pronounced L-DOPA-induced activity, prazosin attenuated the total and duration of activity by 80 and 76%, respectively. These actions of prazosin were expressed in the absence of sedation. Although activation of alpha(1)-adrenoceptors plays no major role in the antiparkinsonian and dyskinetic effects of L-DOPA per se, it does contribute to the induction of hyperactivity. alpha(1)-Adrenoceptors may be involved in pathological responses to L-DOPA treatment, including the dopamine dysregulation syndrome.

  4. Follow-up of cortical activity and structure after lesion with laser speckle imaging and magnetic resonance imaging in nonhuman primates

    NASA Astrophysics Data System (ADS)

    Peuser, Jörn; Belhaj-Saif, Abderraouf; Hamadjida, Adjia; Schmidlin, Eric; Gindrat, Anne-Dominique; Völker, Andreas Charles; Zakharov, Pavel; Hoogewoud, Henri-Marcel; Rouiller, Eric M.; Scheffold, Frank

    2011-09-01

    The nonhuman primate model is suitable to study mechanisms of functional recovery following lesion of the cerebral cortex (motor cortex), on which therapeutic strategies can be tested. To interpret behavioral data (time course and extent of functional recovery), it is crucial to monitor the properties of the experimental cortical lesion, induced by infusion of the excitotoxin ibotenic acid. In two adult macaque monkeys, ibotenic acid infusions produced a restricted, permanent lesion of the motor cortex. In one monkey, the lesion was monitored over 3.5 weeks, combining laser speckle imaging (LSI) as metabolic readout (cerebral blood flow) and anatomical assessment with magnetic resonance imaging (T2-weighted MRI). The cerebral blood flow, measured online during subsequent injections of the ibotenic acid in the motor cortex, exhibited a dramatic increase, still present after one week, in parallel to a MRI hypersignal. After 3.5 weeks, the cerebral blood flow was strongly reduced (below reference level) and the hypersignal disappeared from the MRI scan, although the lesion was permanent as histologically assessed post-mortem. The MRI data were similar in the second monkey. Our experiments suggest that LSI and MRI, although they reflect different features, vary in parallel during a few weeks following an excitotoxic cortical lesion.

  5. Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the nucleus basalis magnocellularis.

    PubMed

    Sanchez-Alavez, Manuel; Ehlers, Cindy L

    2016-05-01

    The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1kHz tones and to release the lever upon hearing a 2kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands, (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Assessment of Independent Risk Factors of Developing Pneumothorax During Percutaneous Core Needle Lung Biopsy: Focus on Lesion Depth

    PubMed Central

    Lee, Ha-Yeon; Lee, In Jae

    2016-01-01

    Background Previous studies identifying risk factors for pneumothorax in percutaneous core needle lung biopsies reported inconsistent and contradictory results. Objectives We aimed to identify independent risk factors for pneumothorax associated with computed tomography (CT)-guided percutaneous core needle lung biopsy (PCNB). Patients and Methods We retrospectively reviewed 591 biopsy procedures for focal lung lesions. Risk factors for pneumothorax as a complication after lung biopsy were determined by univariate and multivariate analyses of variables including the patient’s age, gender, lesion depth from the pleural surface, lesion size, lesion location, presence or absence of fissure crossing by the needle, emphysema in the same lobe where the biopsy was performed, and the final diagnosis of the biopsy lesion. Results Pneumothorax occurred in 100 (16.9%) of 591 procedures. Based on univariate analyses, significant risk factors affecting the incidence of pneumothorax were patient gender (P = 0.039), lesion depth from the pleural surface (P < 0.001), fissure crossing by the needle (P = 0.002), and the presence of emphysema (P = 0.009). From the multivariate analysis, an increased rate of pneumothorax was strongly correlated with lesion depth from the pleural surface (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.50 - 1.96; P < 0.001) and the presence of emphysema (OR, 2.95; 95% CI, 1.73 - 5.04; P < 0.001). Conclusion Lesion depth from the pleural surface and the presence of emphysema were strongly correlated with the increasing incidence of pneumothorax after CT-guided PCNB. Our results may be applicable for the risk management of PCNBs to reduce pneumothorax as a complication. PMID:27895865

  7. Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats.

    PubMed

    Angioni, Laura; Cocco, Cristina; Ferri, Gian-Luca; Argiolas, Antonio; Melis, Maria Rosaria; Sanna, Fabrizio

    2016-07-01

    Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Loading and composite restoration assessment of various non-carious cervical lesions morphologies - 3D finite element analysis.

    PubMed

    Soares, P V; Machado, A C; Zeola, L F; Souza, P G; Galvão, A M; Montes, T C; Pereira, A G; Reis, B R; Coleman, T A; Grippo, J O

    2015-09-01

    The present study analysed the effects of different occlusal loading on premolars displaying various non-carious cervical lesions morphologies, restored (or not) with composites, by 3D finite element analysis. A three-dimensional digital model of a maxillary premolar was generated using CAD software. Three non-carious cervical lesions morphological types were simulated: wedged-shaped, saucer and mixed. All virtual models underwent three loading types (100 N): vertical, buccal and palatal loading. The simulated non-carious cervical lesions morphologies were analysed with and without restorations to consider specific regions, such as the occlusal and gingival walls as well as the depth of the lesions. Data summarizing the stress distribution were obtained in MPa using Maximum Principal Stress. Palatal loads were responsible for providing the highest values of accumulated tensile stress on the buccal wall; 27.66 MPa and 25.76 MPa for mixed and wedged-shaped morphologies, respectively. The highest tensile values found on non-carious cervical lesions morphologies restored with composite resin were 5.9 MPa in the mixed morphology, similar to those found on sound models despite their morphologies and occlusal loading. The various non-carious cervical lesions morphologies had little effect on stress distribution patterns, whereas the loading type and presence of composite restorations influenced the biomechanical behaviour of the maxillary premolars. © 2015 Australian Dental Association.

  9. Assessing Elementary Lesions in Gout by Ultrasound: Results of an OMERACT Patient-based Agreement and Reliability Exercise.

    PubMed

    Terslev, Lene; Gutierrez, Marwin; Christensen, Robin; Balint, Peter V; Bruyn, George A; Delle Sedie, Andrea; Filippucci, Emilio; Garrido, Jesus; Hammer, Hilde B; Iagnocco, Annamaria; Kane, David; Kaeley, Gurjit S; Keen, Helen; Mandl, Peter; Naredo, Esperanza; Pineda, Carlos; Schicke, Bernd; Thiele, Ralf; D'Agostino, Maria Antonietta; Schmidt, Wolfgang A

    2015-11-01

    To test the reliability of the consensus-based ultrasound (US) definitions of elementary gout lesions in patients. Eight patients with microscopically proven gout were evaluated by 16 sonographers for signs of double contour (DC), aggregates, erosions, and tophi in the first metatarsophalangeal joint and the knee bilaterally. The patients were examined twice using B-mode US to test agreement and inter- and intraobserver reliability of the elementary components. The prevalence of the lesions were DC 52.8%, tophus 61.1%, aggregates 29.8%, and erosions 32.4%. The intraobserver reliability was good for all lesions except DC, where it was moderate. The best reliability per lesion was seen for tophus (κ 0.73, 95% CI 0.61-0.85) and lowest for DC (κ 0.53, 95% CI 0.38-0.67). The interobserver reliability was good for tophus and erosions, but fair to moderate for aggregates and DC, respectively. The best reliability was seen for erosions (κ 0.74, 95% CI 0.65-0.81) and lowest for aggregates (κ 0.21, 95% CI 0.04-0.37). This is the first step to test consensus-based US definitions on elementary lesions in patients with gout. High intraobserver reliability was found when applying the definition in patients on all elementary lesions while interobserver reliability was moderate to low. Further studies are needed to improve the interobserver reliability, particularly for DC and aggregates.

  10. Operationalization Of The Professional Risks Assessment Activity

    NASA Astrophysics Data System (ADS)

    Ivascu, Victoria Larisa; Cirjaliu, Bianca; Draghici, Anca

    2015-07-01

    Professional risks assessment approach (integration of analysis and evaluation processes) is linked with the general concerns of nowadays companies for their employees' health and safety assurances, in the context of organizations sustainable development. The paper presents an approach for the operationalization of the professional risk assessment activity in companies through the implementation and use of the OnRisk platform (this have been tested in some industrial companies). The short presentation of the relevant technical reports and statistics on OSH management at the European Union level underlines the need for the development of a professional risks assessment. Finally, there have been described the designed and developed OnRisk platform as a web platform together with some case studies that have validate the created tool.

  11. Needs assessment activity report: Fiscal year 1995

    SciTech Connect

    1995-09-01

    The Needs Assessment program has assessed the packaging requirements of many U.S. Department of Energy (DOE) sites. These assessments have involved site visits and meetings with personnel involved with transportation and packaging of hazardous materials. By September 1995, 24 DOE facilities had been visited, with 14 site visits occurring in fiscal year 1995. As a result, these sites have been informed of some of the packaging activities that DOE has sponsored and is sponsoring, have been apprised of the affects of upcoming changes to transportation regulations, have discussed their near-term packaging needs, and have shared unique packaging they have developed, which may be of use to other DOE facilities. Program successes include discovery of a need for a reusable Type A liquid sample packaging and its development within another DOE task and establishing communications pathways between DOE sites that have similar transportation and packaging needs. This report recommends that the Needs Assessment activity continue to pursue the strategy of visiting DOE sites to meet with their transportation and packaging personnel. These visits will ensure that DOE needs are met, communications pathways between DOE sites are established and cultivated, and redundant packaging development is identified. The site visits should be expanded to include meetings with the long-range and strategic planners at each site, and at the DOE-Headquarters level, to ensure that all future transportation and packaging needs are identified early enough to allow adequate transportation assessment and packaging development. This activity could become a permanent conduit for information and will ensure that all future DOE transportation and packaging needs are satisfied in a cost-effective, timely, and efficient manner.

  12. Global increase in task-related fronto-parietal activity after focal frontal lobe lesion.

    PubMed

    Woolgar, Alexandra; Bor, Daniel; Duncan, John

    2013-09-01

    A critical question for neuropsychology is how complex brain networks react to damage. Here, we address this question for the well-known executive control or multiple-demand (MD) system, a fronto-parietal network showing increased activity with many different kinds of cognitive demand, including standard tests of fluid intelligence. Using fMRI, we ask how focal frontal lobe damage affects MD activity during a standard fluid intelligence task. Despite poor behavioral performance, frontal patients showed increased fronto-parietal activity relative to controls. The activation difference was not accounted for by difference in IQ. Moreover, rather than specific focus on perilesional or contralesional cortex, additional recruitment was distributed throughout the MD regions and surrounding cortex and included parietal MD regions distant from the injury. The data suggest that, following local frontal lobe damage, there is a global compensatory recruitment of an adaptive and integrated fronto-parietal network.

  13. Comparison of frequency domain optical coherence tomography and quantitative coronary angiography for the assessment of coronary lesions

    NASA Astrophysics Data System (ADS)

    Zafar, Haroon; Sharif, Faisal; Leahy, Martin J.

    2014-03-01

    Quantitative coronary angiography (QCA) has been used as a standard technique for the evaluation of coronary artery disease for many years. Intracoronary optical coherence tomography (OCT) offers higher resolution, faster image acquisition speeds and greater sensitivity than the intravascular ultrasound (IVUS). Recently developed frequency domain OCT (FD-OCT) systems overcome many technical limitations of conventional time domain OCT systems (TDOCT). The main objective of this study was to compare the FD-OCT and QCA measurements for the assessment of coronary lesions. A total of 21 stenoses in 18 patients were analysed using QCA and FD-OCT. The average minimum lumen diameter (MLD) and percent lumen area stenosis (%AS) by QCA were 1.52+/-0.44 mm and 68+/-9% respectively. The average MLD and %AS by FD-OCT were 1.32+/-0.38 mm and 63+/-14% respectively. There was a moderate but significant correlation between QCA and FD-OCT measured MLD (r = 0.5, p < 0.01) and %AS (r = 0.56, p < 0.01). Bland-Altman analysis showed that the mean differences between the QCA and FD-OCT measurements were 0.18+/-0.81 (limits of agreement: -0.63 to 0.99) for MLD and 4.4+/-22.8 (limits of agreement: -18.4 to 27.2) for %AS. The root mean square error (RMSE) between the QCA and FD-OCT measured MLD and %AS was +/-0.44 mm and +/-12.1% respectively.

  14. The assessment of tumor response by measuring the single largest lesion per organ in metastatic tumors: a pooled analysis of previously reported data.

    PubMed

    Jang, Hyun Joo; Cho, Ji Woong; Park, Bumjung; Choi, Hyun Chang; Kim, Hyeong Su; Kim, Jung Han

    2015-01-01

    The RECIST 1.1 adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. Recently, we reported that the modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a high level of concordance with the original RECIST 1.1 in patients with advanced or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and colorectal cancer (CRC). However, each study had a major limitation of a small number of patients. We conducted a pooled analysis using the data from the three individual studies to improve statistical power. Tumor responses were compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1). A total of 153 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51 with GC, and 38 with CRC. Regardless of primary sites, the number of target lesions according to the mRECIST 1.1 was significantly lower than that according to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high concordance between the two criteria (k = 0.908). Only eight patients (5.2%) showed disagreement in the tumor response assessment between the two criteria. The overall response rates of chemotherapy were not significantly different between the two criteria (33.3% versus 33.3%, P=1.0). The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response in clinical practice.

  15. Lesion remyelinating activity of GSK239512 versus placebo in patients with relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II study.

    PubMed

    Schwartzbach, Caryl J; Grove, Richard A; Brown, Robert; Tompson, Debra; Then Bergh, Florian; Arnold, Douglas L

    2017-02-01

    Histamine H3 receptor blockade may enhance lesion remyelination in multiple sclerosis (MS). The efficacy (using a magnetic resonance imaging marker of myelination, magnetisation transfer ratio [MTR]), safety and pharmacokinetics of GSK239512, a potent and brain penetrant H3 receptor antagonist/inverse agonist on lesion remyelination in relapsing-remitting MS (RRMS) were assessed. This was a phase II, randomised, parallel-group, placebo-controlled, double-blind (sponsor-unblinded), international, multicentre study (NCT01772199). Patients aged 18-50 with RRMS, receiving intramuscular interferon-β1a or glatiramer acetate, were randomised 1:1 to once-daily oral GSK239512 or placebo, up-titrated over 4-5 weeks to a maximum tolerable dose up to 80 µg and maintained until Week 48. The co-primary endpoints were mean changes in post-lesion MTR in gadolinium-enhanced (GdE) or Delta-MTR defined lesions from pre-lesion values. Adverse events (AE) and withdrawals were monitored. Of the 131 patients randomised, 114 patients completed the study (GSK239512, n = 51; placebo, n = 63) and 27 (GSK239512) and 28 (placebo) patients contributed lesions to the primary analysis. GSK239512 was associated with positive effect sizes of 0.344 [90% confidence interval (CI) 0.018, 0.671] and 0.243 (90% CI -0.112, 0.598) for adjusted mean changes in the normalised MTR for GdE and Delta-MTR lesions, respectively. The overall incidence of AEs was similar between GSK239512 and placebo during the treatment phase although some AEs including insomnia were more common with GSK239512, particularly during the titration period. A small but positive effect of GSK239512 on remyelination was observed. MTR assessment represents a promising method for detecting lesion remyelination in RRMS.

  16. EADB: An Estrogenic Activity Database for Assessing ...

    EPA Pesticide Factsheets

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/ BioinformaticsTools/EstrogenicActivityDatabaseEADB/default. htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of

  17. Relative contributions of local cell and passing fiber activation and silencing to changes in thalamic fidelity during deep brain stimulation and lesioning: a computational modeling study.

    PubMed

    So, Rosa Q; Kent, Alexander R; Grill, Warren M

    2012-06-01

    Deep brain stimulation (DBS) and lesioning are two surgical techniques used in the treatment of advanced Parkinson's disease (PD) in patients whose symptoms are not well controlled by drugs, or who experience dyskinesias as a side effect of medications. Although these treatments have been widely practiced, the mechanisms behind DBS and lesioning are still not well understood. The subthalamic nucleus (STN) and globus pallidus pars interna (GPi) are two common targets for both DBS and lesioning. Previous studies have indicated that DBS not only affects local cells within the target, but also passing axons within neighboring regions. Using a computational model of the basal ganglia-thalamic network, we studied the relative contributions of activation and silencing of local cells (LCs) and fibers of passage (FOPs) to changes in the accuracy of information transmission through the thalamus (thalamic fidelity), which is correlated with the effectiveness of DBS. Activation of both LCs and FOPs during STN and GPi-DBS were beneficial to the outcome of stimulation. During STN and GPi lesioning, effects of silencing LCs and FOPs were different between the two types of lesioning. For STN lesioning, silencing GPi FOPs mainly contributed to its effectiveness, while silencing only STN LCs did not improve thalamic fidelity. In contrast, silencing both GPi LCs and GPe FOPs during GPi lesioning contributed to improvements in thalamic fidelity. Thus, two distinct mechanisms produced comparable improvements in thalamic function: driving the output of the basal ganglia to produce tonic inhibition and silencing the output of the basal ganglia to produce tonic disinhibition. These results show the importance of considering effects of activating or silencing fibers passing close to the nucleus when deciding upon a target location for DBS or lesioning.

  18. Clinical performance of two visual scoring systems in detecting and assessing activity status of occlusal caries in primary teeth.

    PubMed

    Braga, M M; Ekstrand, K R; Martignon, S; Imparato, J C P; Ricketts, D N J; Mendes, F M

    2010-01-01

    This study aimed to compare the clinical performance of two sets of visual scoring criteria for detecting caries severity and assessing caries activity status in occlusal surfaces. Two visual scoring systems--the Nyvad criteria (NY) and the ICDAS-II including an adjunct system for lesion activity assessment (ICDAS-LAA)--were compared using 763 primary molars of 139 children aged 3-12 years. The examinations were performed by 2 calibrated examiners. A subsample (n = 50) was collected after extraction and histology with 0.1% red methyl dye was performed to validate lesion depth and activity. The reproducibility of the indices was calculated (kappa test) and ROC analysis was performed to assess their validity and related parameters were compared using McNemar's test. The association between the indices and with the histological examination was evaluated using Spearman's correlation coefficient (r(s)). Visual criteria showed excellent reproducibility both regarding severity (NY: 0.94; ICDAS-II: 0.91) and activity (NY: 0.90; LAA: 0.91). The NY and LAA showed good association in caries activity assessment (r(s) = 0.88; 95% CI = 0.86-0.89; p < 0.001). Nevertheless, considering only cavitated lesions, this association was not significant (p > 0.05). Concerning the severity, both indices presented similar validity parameters. At D2 threshold, the sensitivity was higher for NY (NY = 0.87; ICDAS = 0.61, p < 0.05). Regarding activity status, NY showed higher specificities and accuracies. In conclusion, NY and ICDAS-II criteria are comparable and present good reproducibility and validity to detect caries lesions and estimate their severities, but the LAA seems to overestimate the caries activity assessment of cavitated lesions compared to NY. Copyright 2010 S. Karger AG, Basel.

  19. Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

    PubMed

    Berchtold, Lena; Ponte, Belen; Moll, Solange; Hadaya, Karine; Seyde, Olivia; Bachtler, Matthias; Vallée, Jean-Paul; Martin, Pierre-Yves; Pasch, Andreas; de Seigneux, Sophie

    2016-01-01

    Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

  20. Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve

    PubMed Central

    2016-01-01

    Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86–0.95 (n = 330), group 3: 0.81–0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1–4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary. PMID:27822931

  1. Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve.

    PubMed

    Won, Ki Bum; Nam, Chang Wook; Cho, Yun Kyeong; Yoon, Hyuck Jun; Park, Hyoung Seob; Kim, Hyungseop; Han, Seongwook; Hur, Seung Ho; Kim, Yoon Nyun; Park, Sang Hyun; Han, Jung Kyu; Koo, Bon Kwon; Kim, Hyo Soo; Doh, Joon Hyung; Lee, Sung Yun; Yang, Hyoung Mo; Lim, Hong Seok; Yoon, Myeong Ho; Tahk, Seung Jea; Kim, Kwon Bae

    2016-12-01

    Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86-0.95 (n = 330), group 3: 0.81-0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1-4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.

  2. Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients

    PubMed Central

    Berchtold, Lena; Ponte, Belen; Moll, Solange; Hadaya, Karine; Seyde, Olivia; Bachtler, Matthias; Vallée, Jean-Paul; Martin, Pierre-Yves; Pasch, Andreas; de Seigneux, Sophie

    2016-01-01

    Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance. PMID:28036331

  3. Role of mast cells, stem cell factor and protease-activated receptor-2 in tubulointerstitial lesions in IgA nephropathy.

    PubMed

    Liu, Hong; Liu, Fuyou; Peng, Youming; Liu, Yinghong; Li, Lingyan; Tu, Xiwen; Cheng, Meichu; Xu, Xiangqing; Chen, Xing; Ling, Guanghui; Sun, Lin

    2010-07-01

    To elucidate the role of mast cells (MCs) in the pathogenesis of tubulointerstitial lesions in IgA nephropathy (IgAN), we investigated the number of MCs, serum stem cell factor (SCF), protease-activated receptor-2 (PAR-2) and alpha-smooth-muscle actin (alpha-SMA) in the kidney and the correlation between MC number, SCF, PAR-2, alpha-SMA and tubulointerstitial lesions in biopsy specimens and serum creatinine levels, urinary protein excretion in patients with IgA nephropathy. Thirty-five patients with IgA nephropathy were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining. Monoclonal antibodies to human tryptase, alpha-SMA, and SCF and polyclonal antibody to PAR-2 were used as primary antibodies. Ten cortical interstitial fields were randomly selected and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. In all of the control subjects, few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions, the expression of SCF, PAR-2 and alpha-SMA were positively correlated with the degree of interstitial fibrosis. A close correlation between MCs, alpha-SMA, PAR-2 and SCF was found (r = 0.887 for alpha-SMA, r = 0.844 for PAR-2, r = 0.853 for SCF, P < 0.01). Also a close correlation between alpha-SMA, PAR-2 and SCF was found (r = 0.874 for PAR-2, r = 0.862 for SCF, P < 0.01). PAR-2 was correlated with SCF (r = 0.893, P < 0.01). Moreover, a significant positive correlation was observed between the number of interstitial MCs, the expression of SCF, PAR-2 and alpha-SMA and the serum

  4. Radiopaque Tagging Masks Caries Lesions following Incomplete Excavation in vitro.

    PubMed

    Schwendicke, F; Meyer-Lueckel, H; Schulz, M; Dörfer, C E; Paris, S

    2014-06-01

    One-step incomplete excavation seals caries-affected dentin under a restoration and appears to be advantageous in the treatment of deep lesions. However, it is impossible to discriminate radiographically between intentionally left, arrested lesions and overlooked or active lesions. This diagnostic uncertainty decreases the acceptance of minimally invasive excavation and might lead to unnecessary re-treatment of incompletely excavated teeth. Radiopaque tagging of sealed lesions might mask arrested lesions and assist in discrimination from progressing lesions. Therefore, we microradiographically screened 4 substances (SnCl2, AgNO3, CsF, CsCH3COO) for their effect on artificial lesions. Since water-dissolved tin chloride (SnCl2×Aq) was found to stably mask artificial lesions, we then investigated its radiographic effects on progressing lesions. Natural lesions were incompletely excavated and radiopaque tagging performed. Grey-value differences (△GV) between sound and carious dentin were determined and radiographs assessed by 20 dentists. While radiographic effects of SnCl2×Aq were stable for non-progressing lesions, they significantly decreased during a second demineralization (p < .001, t test). For natural lesions, tagging with SnCl2×Aq significantly reduced △GV (p < .001, Wilcoxon). Tagged lesions were detected significantly less often than untagged lesions (p < .001). SnCl2×Aq was suitable to mask caries-affected dentin and discriminate between arrested and progressing lesions in vitro. Radiopaque tagging could resolve diagnostic uncertainties associated with incomplete excavation.

  5. EADB: an estrogenic activity database for assessing potential endocrine activity.

    PubMed

    Shen, Jie; Xu, Lei; Fang, Hong; Richard, Ann M; Bray, Jeffrey D; Judson, Richard S; Zhou, Guangxu; Colatsky, Thomas J; Aungst, Jason L; Teng, Christina; Harris, Steve C; Ge, Weigong; Dai, Susie Y; Su, Zhenqiang; Jacobs, Abigail C; Harrouk, Wafa; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2013-10-01

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.

  6. Acute bony bankart lesion and surgical fixation.

    PubMed

    Rosenthal, Michael D; Provencher, Matthew T

    2009-10-01

    The patient was a 25-year-old man who sustained a traumatic left anterior shoulder dislocation. After self-reducing the first time, as well as in subsequent repeated dislocations over the following 2-day period, the patient reported his injury to the medical staff, who sent him to the physical therapist for evaluation. Anterior-posterior, scapular outlet, and axillary radiographic views demonstrated a bony glenoid lesion consistent with a bony Bankart lesion, which was best seen on the scapular outlet view. A 3-dimensional computed tomography scan was performed to assess the size and displacement of the bony Bankart lesion. Six days following injury, the patient underwent operative fixation of the bony Bankart lesion. Following surgery, the patient completed 5 months of physical therapy and subsequently returned to high-demand upper body activities. At 3 years following surgery, the patient reported full functional ability without shoulder instability or pain.

  7. PS-OCT of natural pigmented and nonpigmented interproximal caries lesions

    NASA Astrophysics Data System (ADS)

    Ngaotheppitak, Patara; Darling, Cynthia L.; Fried, Daniel

    2005-03-01

    Previous studies have demonstrated that Polarization Sensitive Optical Coherence Tomography (PS-OCT) can be used to image early dental caries. The purpose of this study was to compare the measured reflectivity of natural caries lesions with the mineral loss measured using digital microradiography. An all polarization-maintaining fiber based PS-OCT system operating at 1310-nm was used to acquire polarization resolved images of natural white spot lesions and pigmented lesions on the smooth surfaces of extracted teeth. There was a strong positive correlation between the increase in the integrated reflectivity in the perpendicular polarization axis of the PS-OCT system and the increase in the integrated mineral loss or lesion severity for both white-spot and pigmented lesions, P <0.001. Therefore, PS-OCT is well-suited to assess the severity of natural caries lesions and resolve the internal structure of early caries lesions for the potential assessment of the lesion activity.

  8. DNA double-strand breaks and ATM activation by transcription-blocking DNA lesions.

    PubMed

    Sordet, Olivier; Nakamura, Asako J; Redon, Christophe E; Pommier, Yves

    2010-01-15

    A taxia telangiectasia mutated (ATM), the deficiency of which causes a severe neurodegenerative disease, is a crucial mediator for the DNA double-strand break (DSB) response. We recently showed that transcription-blocking topoisomerase I cleavage complexes (TOP1cc) produce DSBs related to R-loop formation and activate ATM in post-mitotic neurons and lymphocytes. Here we discuss how TOP1cc can produce transcription arrest with R-loop formation and generate DSBs that activate ATM, as well as data suggesting that those transcription-dependent DSBs tend to form at the IgH locus and at specific genomic sites. We also address the potential roles of ATM in response to transcription-blocking TOP1cc.

  9. Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals

    PubMed Central

    2014-01-01

    Background Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural “intent”. A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of “intent” may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. Methods We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called “Motolink”, which detects these neural patterns and triggers a “spinal” stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for “Motolink” hardware. Results We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the “Motolink” system to detect the neural “intent” of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. Conclusion We present a direct cortical “intent”-driven electronic spinal

  10. Reversal of active glomerular lesions after immunosuppressive therapy in patients with IgA nephropathy: a repeat-biopsy based observation.

    PubMed

    Shen, Xia-Hong; Liang, Shao-Shan; Chen, Hui-Mei; Le, Wei-Bo; Jiang, Song; Zeng, Cai-Hong; Zhou, Min-Lin; Zhang, Hai-Tao; Liu, Zhi-Hong

    2015-08-01

    Reversal of active glomerular lesions after immunosuppressive treatment in patients with IgA nephropathy (IgAN) and their association with prognosis have not been well established. Sixty patients with IgAN who received repeat biopsies after immunosuppressive treatment were recruited. Reversal of renal pathological lesions was evaluated between the first and second biopsy. The end-point was defined as a 30% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease after the second biopsy. Active glomerular lesions, i.e. endocapillary hypercellularity (E), crescents (C) and necrosis (N) were markedly decreased at the second biopsy after immunosuppressive therapy (36.7 vs. 8.3%, p < 0.001; 85.0 vs. 25.0%, p < 0.001; and 51.7 vs. 3.3%, p < 0.001). Patients with E, C or N at the first biopsy but reversed at the second biopsy showed significantly decreased median levels of proteinuria and hematuria. Such clinical changes were not observed in those with active lesions at both biopsies. After a median follow-up of 32 months, 25.0% of patients reached the end-point. Repeat biopsy confirmed that only tubular atrophy/interstitial fibrosis was associated with the renal outcome. Active glomerular lesions can be reversed by immunosuppressive treatment in patients with IgAN. The reversal is accompanied by improvement in proteinuria and hematuria. The reversal of these lesions during the disease process may explain the lack of significant correlation of these lesions with clinical outcomes in the present study as well as in previous evaluation studies of the Oxford classification of IgAN.

  11. The relative contribution of magnetic resonance imaging to the assessment and differential diagnosis of cerebellopontine angle mass lesions.

    PubMed

    Worthington, B S; Mawhinney, R R; Holland, I M; Lowe, J; Punt, J; Bydder, G; Young, I R

    1986-01-01

    Forty-nine patients with a space occupying lesion in the cerebellopontine angle cistern were examined by computed tomography (CT), magnetic imaging (MRI) and, where appropriate, conventional neuroradiologic techniques. The presence of an intracanalicular extension and a high signal on T2 weighted sequences were typical of acoustic neuroma and allowed separation from meningioma. Contrast enhancement with gadolinium DTPA was particularly valuable in recurrent acoustic neuroma. Typically epidermoids had long T1 and T2 values. Sequences which highlight flow allow vascular lesions to be identified without the use of contrast media. In separating the several pathologies MRI was superior to CT and also gave information on tissue composition in acoustic neuroma.

  12. Endonuclease and Exonuclease Activities on Oligodeoxynucleotides Containing Spiroiminodihydantoin Depend on the Sequence Context and the Lesion Stereochemistry

    PubMed Central

    Chen, Xin; Fleming, Aaron M.; Muller, James G.; Burrows, Cynthia J.

    2013-01-01

    8-Oxo-7,8-dihydro-2′-deoxyguanosine (dOG), a well-studied oxidation product of 2′-deoxyguanosine (dG), is prone to facile further oxidation forming spiroiminodihydantoin 2′-deoxyribonucleoside (dSp) in the nucleotide pool and in single-stranded oligodeoxynucleotides (ODNs). Many methods for quantification of damaged lesions in the genome rely on digestion of DNA with exonucleases or endonucleases and dephosphorylation followed by LC-MS analysis of the resulting nucleosides. In this study, enzymatic hydrolysis of dSp-containing ODNs was investigated with snake venom phosphodiesterase (SVPD), spleen phosphodiesterase (SPD) and nuclease P1. SVPD led to formation of a dinucleotide, 5′-d(Np[Sp])-3′ (N = any nucleotide) that included the undamaged nucleotide on the 5′ side of dSp as the final product. This dinucleotide was a substrate for both SPD and nuclease P1. A kinetic study of the activity of SPD and nuclease P1 showed a sequence dependence on the nucleotide 5′ to the lesion with rates in the order dG>dA>dT>dC. In addition, the two diastereomers of dSp underwent digestion at significantly different rates with dSp1>dSp2; nuclease P1 hydrolyzed the 5′-d(Np[Sp1])-3′ dinucleotide two- to six-fold faster than the corresponding 5′-d(Np[Sp2])-3′, while for SPD the difference was two-fold. These rates are chemically reasoned based on dSp diastereomer differences in the syn vs. anti glycosidic bond orientation. A method for the complete digestion of dSp-containing ODNs is also outlined based on treatment with nuclease P1 and SVPD. These findings have significant impact on the development of methods to detect dSp levels in cellular DNA. PMID:24563606

  13. Mutant of herpes simplex virus type 2 with temperature-sensitive lesions affecting virion thermostability and DNase activity: identification of the lethal mutation and physical mapping of the nuc-lesion.

    PubMed Central

    Chartrand, P; Timbury, M C; Hay, J; Moss, H

    1979-01-01

    We had previously shown that a temperature-sensitive (ts) mutant of herpes simplex virus type 2 strain HG52, ts13, induced a heat-labile DNase activity in infected cells (B. Francke, H. Moss, M. C. Timbury, and J. Hay, J. Virol. 26:209-213, 1978). Earlier work indicated that the mutant also possessed temperature-sensitive infectivity (I. W. Halliburton and M. C. Timbury, J. Gen. Virol. 30:207-221, 1976). In this study temperature-stable revertants of ts13 have been isolated; examination of them revealed that ts13 is a double mutant, with genetically distinct temperature-sensitive lesions affecting nuclease activity and particle stability. The lethal mutation, in the cell system studied, is the latter. Revertants, which all maintain the nuclease lesion, grew well at a high temperature. Physical mapping of the nuclease lesion placed it between 0.12 and 0.21 (fractional length) on the virus genome, quite distant from the lethal mutation at 0.64 to 0.70. PMID:232166

  14. Aging assessment for active fire protection systems

    SciTech Connect

    Ross, S.B.; Nowlen, S.P.; Tanaka, T.

    1995-06-01

    This study assessed the impact of aging on the performance and reliability of active fire protection systems including both fixed fire suppression and fixed fire detection systems. The experience base shows that most nuclear power plants have an aggressive maintenance and testing program and are finding degraded fire protection system components before a failure occurs. Also, from the data reviewed it is clear that the risk impact of fire protection system aging is low. However, it is assumed that a more aggressive maintenance and testing program involving preventive diagnostics may reduce the risk impact even further.

  15. Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: an animal model of motor disorders in sleep.

    PubMed

    Lai, Y-Y; Hsieh, K-C; Nguyen, D; Peever, J; Siegel, J M

    2008-06-23

    There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.

  16. A randomized trial to evaluate the effect of a trace mineral premix on the incidence of active digital dermatitis lesions in cattle.

    PubMed

    Gomez, A; Bernardoni, N; Rieman, J; Dusick, A; Hartshorn, R; Read, D H; Socha, M T; Cook, N B; Döpfer, D

    2014-10-01

    A balanced, parallel-group, single-blinded randomized efficacy study divided into 2 periods was conducted to evaluate the effect of a premix containing higher than typically recommended levels of organic trace minerals and iodine (HOTMI) in reducing the incidence of active digital dermatitis (DD) lesions acquired naturally and induced by an experimental infection challenge model. For the natural exposure phase of the study, 120 healthy Holstein steers 5 to 7 mo of age without signs of hoof disease were randomized into 2 groups of 60 animals. The control group was fed a standard trace mineral supplement and the treatment group was fed the HOTMI premix, both for a period of 60 d. On d 60, 15 steers free of macroscopic DD lesions were randomly selected from each group for the challenge phase and transported to an experimental facility, where they were acclimated and then challenged within a DD infection model. The same diet group allocation was maintained during the 60 d of the challenge phase. The primary outcome measured was the development of an active DD lesion greater than 20mm in diameter across its largest dimension. No lesions were identified during the natural exposure phase. During the challenge phase, 55% (11/20) and 30% (6/20) of feet were diagnosed with an active DD lesion in the control and treatment groups, respectively. Diagnosis of DD was confirmed by histopathologic demonstration of invasive Treponema spp. within eroded and hyperplastic epidermis and ulcerated papillary dermis. All DD confirmed lesions had dark-field microscopic features compatible with DD and were positive for Treponema spp. by PCR. As a secondary outcome, the average DD lesion size observed in all feet was also evaluated. Overall mean (standard deviation) lesion size was 17.1 (2.36) mm and 11.1 (3.33) mm for the control and treatment groups, respectively, with this difference being driven by acute DD lesions >20mm. A trend existed for the HOTMI premix to reduce the total DD

  17. Activated myeloid dendritic cells accumulate and co-localize with CD3+ T cells in coronary artery lesions in patients with Kawasaki disease.

    PubMed

    Yilmaz, Atilla; Rowley, Anne; Schulte, Danica J; Doherty, Terence M; Schröder, Nicolas W J; Fishbein, Michael C; Kalelkar, Mitra; Cicha, Iwona; Schubert, Katja; Daniel, Werner G; Garlichs, Christoph D; Arditi, Moshe

    2007-08-01

    Emerging evidence implicating the participation of dendritic cells (DCs) and T cells in various vascular inflammatory diseases such as giant cell arteritis, Takayasu's arteritis, and atherosclerosis led us to hypothesize that they might also participate in the pathogenesis of coronary arteritis in Kawasaki disease (KD). Coronary artery specimens from 4 patients with KD and 6 control patients were obtained. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect all myeloid DCs (S-100(+), fascin(+)), all plasmacytoid DCs (CD123(+)) as well as specific DC subsets (mature myeloid DCs [CD83(+)], myeloid [BDCA-1(+)] and plasmacytoid DC precursors [BDCA-2(+)]), T cells (CD3(+)), and all antigen-presenting cells (HLA-DR(+)). Co-localization of DCs with T cells was assessed using double immunostaining. Significantly more myeloid DCs at a precursor, immature or mature stage were found in coronary lesions of KD patients than in controls. Myeloid DC precursors were distributed equally in the intima and adventitia. Mature myeloid DCs were particularly abundant in the adventitia. There was a significant correlation between mature DCs and HLA-DR expression. Double immunostaining demonstrated frequent contacts between myeloid DCs and T cells in the outer media and adventitia. Plasmacytoid DC precursors were rarely found in the adventitia. In conclusion, coronary artery lesions of KD patients contain increased numbers of mature myeloid DCs with high HLA-DR expression and frequent T cell contacts detected immunohistochemically. This suggests that mature arterial myeloid DCs might be activating T cells in situ and may be a significant factor in the pathogenesis of coronary arteritis in KD.

  18. Effective staining method with iodine for leukoplakia and lesions surrounding squamous cell carcinomas of the tongue assessed by colorimetric analysis.

    PubMed

    Maeda, Keiko; Yamashiro, Masashi; Michi, Yasuyuki; Suzuki, Tetsuo; Ohyama, Yoshio; Okada, Norihiko; Amagasa, Teruo

    2009-12-01

    To determine whether staining with iodine solution provides an efficient criterion for determining the area of resection for the lesions surrounding squamous cell carcinoma (SCC) and leukoplakia of the tongue, we determined the optimum density of iodine solution and staining procedure and analyzed the color of lightly stained lesions (LSLs) in relation to the histopathologic findings. Sixty-five patients with SCC or leukoplakia of the tongue were divided into two groups: lesions stained with 3% Lugol solution and restained with either 5% Lugol solution (n=38) or 10% iodine glycerin (n=27). Among the lesions stained with 5% Lugol solution, significant differences were found in all color values. Color difference values (DeltaE*ab) using 3% and 5% Lugol solutions were significantly different between epithelial hyperplasia/mild epithelial dysplasia and moderate to severe dysplasia (P < 0.05). According to the evaluations of five clinicians in 46 LSLs, a distinctive boundary was most often obtained using 5% Lugol solution. These results suggest that the most effective method for obtaining a clear boundary and distinguishing moderate to severe dysplasia from mild or no epithelial dysplasia according to the measured color value was to stain with 3% followed by 5% Lugol solution.

  19. Effect of ibotenate lesions of the ventromedial hypothalamus on the water and salt intake induced by activation of the median preoptic nucleus in sodium-depleted rats.

    PubMed

    do Vale, C F; Camargo, G M; Saad, W A; Menani, J V; Renzi, A; Luiz, A C; Cerri, P S; Camargo, L A

    1997-09-10

    In this study we investigated the influence of a ventromedial hypothalamus (VMH) lesion with ibotenic acid on water and sodium intake and pressor responses induced by combined treatment of the median preoptic nucleus (MnPO) with angiotensin II (ANG II) and adrenergic agonists (phenylephrine, norepinephrine, isoproterenol and clonidine). Male Holtzman rats with a stainless steel cannula implanted into the MnPO and bilateral sham (vehicle) or VMH lesions with ibotenic acid were used. The ingestion of water and sodium and mean arterial pressure (MAP) were determined in separate groups submitted to sodium depletion with the diuretic furosemide (20 mg/rat). ANG II (10 pmol) injection into the MnPO of sham-lesioned rats induced water and sodium intake and pressor responses. VMH-lesion reduced ANG II-induced water intake and increased saline intake. In sham rats phenylephrine (80 nmol) into MnPO increased, whereas norepinephrine (80 nmol) and clonidine (40 nmol) reduced ANG II-induced water intake while sodium intake was reduced only by clonidine into MnPO. In VMH-lesioned rats, phenylephrine reduced, noradrenaline increased and clonidine produced no effect on ANG II-induced water intake. In lesioned rats ANG II-induced sodium intake was reduced by phenylephrine and noradrenaline, whereas clonidine produced no change. ANG II-induced pressor response was reduced in VMH-lesioned rats, but the pressor response combining ANG II and phenylephrine or noradrenaline in VMH-lesioned rats was bigger than sham rats. These results show that the VMH is important for the changes in water and sodium intake and cardiovascular responses induced by angiotensinergic and adrenergic activation of the MnPO.

  20. Comparison and Combination of Strain and Shear Wave Elastography of Breast Masses for Differentiation of Benign and Malignant Lesions by Quantitative Assessment: Preliminary Study.

    PubMed

    Seo, Mirinae; Ahn, Hye Shin; Park, Sung Hee; Lee, Jong Beum; Choi, Byung Ihn; Sohn, Yu-Mee; Shin, So Youn

    2017-07-08

    To compare the diagnostic performance of strain and shear wave elastography of breast masses for quantitative assessment in differentiating benign and malignant lesions and to evaluate the diagnostic accuracy of combined strain and shear wave elastography. Between January and February 2016, 37 women with 45 breast masses underwent both strain and shear wave ultrasound (US) elastographic examinations. The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) final assessment on B-mode US imaging was assessed. We calculated strain ratios for strain elastography and the mean elasticity value and elasticity ratio of the lesion to fat for shear wave elastography. Diagnostic performances were compared by using the area under the receiver operating characteristic curve (AUC). The 37 women had a mean age of 47.4 years (range, 20-79 years). Of the 45 lesions, 20 were malignant, and 25 were benign. The AUCs for elasticity values on strain and shear wave elastography showed no significant differences (strain ratio, 0.929; mean elasticity, 0.898; and elasticity ratio, 0.868; P > .05). After selectively downgrading BI-RADS category 4a lesions based on strain and shear wave elastographic cutoffs, the AUCs for the combined sets of B-mode US and elastography were improved (B-mode + strain, 0.940; B-mode + shear wave; 0.964; and B-mode, 0.724; P < .001). Combined strain and shear wave elastography showed significantly higher diagnostic accuracy than each individual elastographic modality (P = .031). These preliminary results showed that strain and shear wave elastography had similar diagnostic performance. The addition of strain and shear wave elastography to B-mode US improved diagnostic performance. The combination of strain and shear wave elastography results in a higher diagnostic yield than each individual elastographic modality. © 2017 by the American Institute of Ultrasound in Medicine.

  1. Studies of intestinal lymphoid tissue. VII. The secondary nature of lymphoid cell "activation" in the jejunal lesion of tropical sprue.

    PubMed Central

    Marsh, M. N.; Mathan, M.; Mathan, V. I.

    1983-01-01

    Morphometric techniques were used in the evaluation of lymphocyte morphology and activity in tropical sprue. jejunal biopsies from control subjects (8), patients with epidemic disease (7), patients with endemic disease (11), and subjects who had recovered from sprue (4) were analyzed blindly. In patients with sprue, lymphocytes were increased significantly within crypt (but not surface) epithelium. Immunoblasts (greater than 6 mu in diameter) were increased by 5% over control subjects. Group means for lymphocytic mitotic indexes were also significantly raised, while flux ratios only differed significantly between endemic sprue patients and control subjects. The lymphocytic infiltration was distributed focally in the upper crypt and crypt-villus interzones. Analysis of epidemic cases (presenting within 4-28 days) revealed detectable changes in lymphocyte behavior only after 3 weeks' illness, whereas mucosal lesions and malabsorption were already established during the first week. These data indicate that lymphocyte activation, suggestive of a local cell-mediated immune reaction, does occur in tropical sprue but is secondary to damage already inflicted on enterocytes and their function. Images Figure 3 Figure 4 Figure 5 PMID:6614143

  2. Targeted expression of activated Rac3 in mammary epithelium leads to defective postlactational involution and benign mammary gland lesions.

    PubMed

    Leung, Karen; Nagy, Andre; Gonzalez-Gomez, Ignacio; Groffen, John; Heisterkamp, Nora; Kaartinen, Vesa

    2003-01-01

    Rac3, a novel member of the Rho subfamily of the small GTPases, is frequently activated in cultured breast cancer cells and has been shown to mediate its effect via the p21-activated kinase (Pak) pathway. In order to evaluate these findings in vivo, we generated transgenic mice that express human constitutively active V12Rac under the control of the mouse mammary tumor virus (MMTV) promoter, which targets the transgene expression to the mammary epithelium. V12Rac3 expression could be detected during the first pregnancy, and the transgenic mammary gland tissues displayed an elevated Pak1 phosphorylation. Although milk proteins, beta-casein and whey acidic protein were expressed and milk fat globules accumulated normally during pregnancy, 60% of transgenic mothers failed to nurse their pups. Surprisingly, although full lactational differentiation was never achieved in transgenic mice, gland involution was incomplete. For 5 days after weaning, involution was normal, but thereafter, epithelial islands characteristic of this early stage of involution persisted for months. The apoptotic index decreased after 5 days, and these glands were associated with increased p38 MAPK phosphorylation. Nine months postpartum, the transgenic mammary glands still demonstrated a large amount of persistent epithelial islands and abnormally large ducts with lymphocyte infiltration, whereas the tissues of non-transgenic controls had returned to their normal 'virgin-like' phenotype. These data show that sustained activation of Rac3 in the mammary epithelium leads to impaired mammary gland physiology and results in the formation of mammary gland lesions. Copyright 2003 S. Karger AG, Basel

  3. How to assess sympathetic activity in humans.

    PubMed

    Grassi, G; Esler, M

    1999-06-01

    Sympathetic factors play a central role not only in cardiovascular homeostatic control but also in the pathogenesis and/or in the progression of several cardiovascular diseases, such as essential hypertension, myocardial infarction, cardiac arrhythmias and congestive heart failure. This explains why assessment of adrenergic neural function in humans has been, and certainly still remains, one of the major fields in cardiovascular research. The present paper will review in detail the haemodynamic, pharmacological, biochemical, neurophysiological, neurochemical and neural imaging techniques by which sympathetic activity is assessed in humans, highlighting the main advantages and limitations of each of them. Although plasma noradrenaline measurement represents a useful guide to assess sympathetic neural function, direct recording of sympathetic nerve traffic via microneurography and noradrenaline radiotracer methods have in recent years largely supplanted the plasma noradrenaline approach. This is because they allow (1) discrimination between the central or peripheral nature of increased plasma noradrenaline levels, and (2) precise estimation of the behaviour of regional sympathetic neural function both under physiological and pathological conditions. In contrast, the approach based on spectral analysis of heart rate and blood pressure signals has been shown to have important limitations which prevent the method from faithfully reflecting sympathetic cardiovascular drive. Neural imaging techniques, which require expensive technical support, allow direct visualization of sympathetic enervation of human organs, thus providing information on the 'in vivo' metabolism of noradrenaline in different cardiovascular districts. Although technical improvements have allowed a more precise assessment of human adrenergic function, no technique so far available can be viewed as a 'gold standard' with which the others might be compared. Limitations and disadvantages of the various

  4. Evaluation of methods to assess physical activity

    NASA Astrophysics Data System (ADS)

    Leenders, Nicole Y. J. M.

    Epidemiological evidence has accumulated that demonstrates that the amount of physical activity-related energy expenditure during a week reduces the incidence of cardiovascular disease, diabetes, obesity, and all-cause mortality. To further understand the amount of daily physical activity and related energy expenditure that are necessary to maintain or improve the functional health status and quality of life, instruments that estimate total (TDEE) and physical activity-related energy expenditure (PAEE) under free-living conditions should be determined to be valid and reliable. Without evaluation of the various methods that estimate TDEE and PAEE with the doubly labeled water (DLW) method in females there will be eventual significant limitations on assessing the efficacy of physical activity interventions on health status in this population. A triaxial accelerometer (Tritrac-R3D, (TT)), an uniaxial (Computer Science and Applications Inc., (CSA)) activity monitor, a Yamax-Digiwalker-500sp°ler , (YX-stepcounter), by measuring heart rate responses (HR method) and a 7-d Physical Activity Recall questionnaire (7-d PAR) were compared with the "criterion method" of DLW during a 7-d period in female adults. The DLW-TDEE was underestimated on average 9, 11 and 15% using 7-d PAR, HR method and TT. The underestimation of DLW-PAEE by 7-d PAR was 21% compared to 47% and 67% for TT and YX-stepcounter. Approximately 56% of the variance in DLW-PAEE*kgsp{-1} is explained by the registration of body movement with accelerometry. A larger proportion of the variance in DLW-PAEE*kgsp{-1} was explained by jointly incorporating information from the vertical and horizontal movement measured with the CSA and Tritrac-R3D (rsp2 = 0.87). Although only a small amount of variance in DLW-PAEE*kgsp{-1} is explained by the number of steps taken per day, because of its low cost and ease of use, the Yamax-stepcounter is useful in studies promoting daily walking. Thus, studies involving the

  5. Effect of vessel size on creation of hepatic radiofrequency lesions in pigs: assessment of the "heat sink" effect.

    PubMed

    Lu, David S K; Raman, Steven S; Vodopich, Darko J; Wang, Michael; Sayre, James; Lassman, Charles

    2002-01-01

    The effect of vessels and their size on radiofrequency lesion creation in the liver was evaluated with respect to potential for vascular injury and perfusion-mediated "heat sink" effect. Radiofrequency lesions targeted to tissue adjacent to a variety of vessels were created in vivo in the liver of 10 Yorkshire pigs. Postablation contrast-enhanced CT and then histopathologic analysis of the vessels and lesions were performed after sacrifice of the pigs. Degree of vascular injury and viability of perivascular hepatocytes were recorded and tabulated according to vessel size for both CT and histologic data sets. At CT, 42 (95%) of 44 veins greater than 3 mm remained patent, and four (20%) of 20 veins less than 3 mm were occluded. Heat sink effect, indicated by invagination of enhancing tissue between vessel and radiofrequency lesion, was observed in 32 (73%) of 44 veins greater than 3 mm and in zero of 20 veins less than 3 mm. On histopathology, 111 (100%) of 111 vessels less than 3 mm showed at least partial vessel wall injury, characterized by endothelial cell necrosis and luminal thrombus. In 24 vessels greater than 3 mm, the extent of vessel wall injury decreased with increasing vessel diameter. Viable perivascular tissue indicative of heat sink effect was identified in 12 of 24 veins greater than 3 mm, increasing to seven of seven veins greater than 5 mm. None of 96 vessels less than 2 mm and three of 111 vessels less than 3 mm showed any heat sink effect. There appears to be a narrow transition zone for hepatic vessels at 2-4 mm, beyond which the heat sink effect was seen consistently and substantial vascular injury was rare.

  6. Pink lesions.

    PubMed

    Giacomel, Jason; Zalaudek, Iris

    2013-10-01

    Dermoscopy (dermatoscopy or surface microscopy) is an ancillary dermatologic tool that in experienced hands can improve the accuracy of diagnosis of a variety of benign and malignant pigmented skin tumors. The early and more accurate diagnosis of nonpigmented, or pink, tumors can also be assisted by dermoscopy. This review focuses on the dermoscopic diagnosis of pink lesions, with emphasis on blood vessel morphology and pattern. A 3-step algorithm is presented, which facilitates the timely and more accurate diagnosis of pink tumors and subsequently guides the management for such lesions.

  7. A modeling-based assessment of acousto-optic sensing for monitoring high-intensity focused ultrasound lesion formation

    NASA Astrophysics Data System (ADS)

    Adams, Matthew Tyler

    Real-time acousto-optic (AO) sensing---a dual-wave modality that combines ultrasound with diffuse light to probe the optical properties of turbid media---has been demonstrated to non-invasively detect changes in ex vivo tissue optical properties during high-intensity focused ultrasound (HIFU) exposure. The AO signal indicates the onset of lesion formation and predicts resulting lesion volumes. Although proof-of-concept experiments have been successful, many of the underlying parameters and mechanisms affecting thermally induced optical property changes and the AO detectability of HIFU lesion formation are not well understood. In thesis, a numerical simulation was developed to model the AO sensing process and capture the relevant acoustic, thermal, and optical transport processes. The simulation required data that described how optical properties changed with heating. Experiments were carried out where excised chicken breast was exposed to thermal bath heating and changes in the optical absorption and scattering spectra (500 nm--1100 nm) were measured using a scanning spectrophotometer and an integrating sphere assembly. Results showed that the standard thermal dose model currently used for guiding HIFU treatments needs to be adjusted to describe thermally induced optical property changes. To model the entire AO process, coupled models were used for ultrasound propagation, tissue heating, and diffusive light transport. The angular spectrum method was used to model the acoustic field from the HIFU source. Spatial-temporal temperature elevations induced by the absorption of ultrasound were modeled using a finite-difference time-domain solution to the Pennes bioheat equation. The thermal dose model was then used to determine optical properties based on the temperature history. The diffuse optical field in the tissue was then calculated using a GPU-accelerated Monte Carlo algorithm, which accounted for light-sound interactions and AO signal detection. The simulation was

  8. 42 CFR 460.140 - Additional quality assessment activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Additional quality assessment activities. 460.140... FOR THE ELDERLY (PACE) Quality Assessment and Performance Improvement § 460.140 Additional quality assessment activities. A PACE organization must meet external quality assessment and reporting requirements...

  9. 42 CFR 460.140 - Additional quality assessment activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Additional quality assessment activities. 460.140... FOR THE ELDERLY (PACE) Quality Assessment and Performance Improvement § 460.140 Additional quality assessment activities. A PACE organization must meet external quality assessment and reporting requirements...

  10. Successful Nonoperative Management of HAGL (Humeral Avulsion of Glenohumeral Ligament) Lesion With Concurrent Axillary Nerve Injury in an Active-Duty US Navy SEAL.

    PubMed

    Ernat, Justin J; Bottoni, Craig R; Rowles, Douglas J

    2016-01-01

    Humeral avulsion of the glenohumeral ligament (HAGL) is a lesion that has been recognized as a cause of recurrent shoulder instability. To our knowledge there are no reports of successful return to full function in young, competitive athletes or return to manual labor following nonoperative management of a HAGL lesion. A 26-year-old Navy SEAL was diagnosed with a HAGL injury, and associated traction injury of the axillary nerve as well as a partial tear of the rotator cuff. Operative intervention was recommended; however, due to issues with training and with inability to properly rehab with the axillary nerve injury, surgical plans were delayed. Interestingly, the patient demonstrated both clinical and radiographic magnetic resonance imaging healing of his lesion over an 18-month period. At 18 months the patient had returned to full active duty without pain or instability as a Navy SEAL.

  11. Assessment of a Diagnostic Predictive Probability Model Provided by a Multispectral Digital Skin Lesion Analysis Device for Melanoma and Other High-risk Pigmented Lesions and its Impact on Biopsy Decisions

    PubMed Central

    Yoo, Jane; Tucker, Natalie; White, Richard; Rigel, Darrell S.

    2014-01-01

    Objective: Risk prediction models for primary malignant melanoma thus far have relied on qualitative patient information. The authors propose a quantitative diagnostic predictive probability model using Multispectral Digital Skin Lesion Analysis for melanoma and other high-risk pigmented lesions and evaluate its effectiveness optimizing biopsy decisions by dermatologists. Design: Data from 1,632 pigmented lesions analyzed by a Multispectral Digital Skin Lesion Analysis device were used to perform a logistic regression analysis. This new quantitative melanoma or melanoma/atypical melanocytic hyperplasia/high-grade dysplastic nevus probability model was then evaluated to determine its impact on dermatologist decisions to biopsy pigmented lesions clinically suggestive of melanoma. Participants were given an electronic keypad and answered “yes” or “no” if they would biopsy each of 12 pigmented lesions when presented first with patient history, clinical images, and dermoscopic images and again when subsequently shown Multispectral Digital Skin Lesion Analysis data. Setting/participants: Study of 191 dermatologists at a medical conference. Measurements: Sensitivity, specificity, biopsy accuracy, overall biopsy rate, and percentage dermatologists biopsying all five melanomas. Results: Dermatologists were significantly more sensitive, specific, and accurate while decreasing overall biopsy rates with Multispectral Digital Skin Lesion Analysis probability information. Conclusion: Integration of Multispectral Digital Skin Lesion Analysis probability information in the biopsy evaluation and selection process of pigmented lesions has the potential to improve melanoma sensitivity of dermatologists without the concomitant costs associated with additional biopsies being performed. PMID:25584133

  12. A Method for Extracting Suspected Parotid Lesions in CT Images using Feature-based Segmentation and Active Contours based on Stationary Wavelet Transform

    NASA Astrophysics Data System (ADS)

    Wu, T. Y.; Lin, S. F.

    2013-10-01

    Automatic suspected lesion extraction is an important application in computer-aided diagnosis (CAD). In this paper, we propose a method to automatically extract the suspected parotid regions for clinical evaluation in head and neck CT images. The suspected lesion tissues in low contrast tissue regions can be localized with feature-based segmentation (FBS) based on local texture features, and can be delineated with accuracy by modified active contour models (ACM). At first, stationary wavelet transform (SWT) is introduced. The derived wavelet coefficients are applied to derive the local features for FBS, and to generate enhanced energy maps for ACM computation. Geometric shape features (GSFs) are proposed to analyze each soft tissue region segmented by FBS; the regions with higher similarity GSFs with the lesions are extracted and the information is also applied as the initial conditions for fine delineation computation. Consequently, the suspected lesions can be automatically localized and accurately delineated for aiding clinical diagnosis. The performance of the proposed method is evaluated by comparing with the results outlined by clinical experts. The experiments on 20 pathological CT data sets show that the true-positive (TP) rate on recognizing parotid lesions is about 94%, and the dimension accuracy of delineation results can also approach over 93%.

  13. Characterization of Lesion Formation and Bubble Activities during High Intensity Focused Ultrasound Ablation using Temperature-Derived Parameters

    PubMed Central

    Hsiao, Yi-Sing; Kumon, Ronald E.; Deng, Cheri X.

    2013-01-01

    Successful high-intensity focused ultrasound (HIFU) thermal tissue ablation relies on accurate information of the tissue temperature and tissue status. Often temperature measurements are used to predict and monitor the ablation process. In this study, we conducted HIFU ablation experiments with ex vivo porcine myocardium tissue specimens to identify changes in temperature associated with tissue coagulation and bubble/cavity formation. Using infrared (IR) thermography and synchronized bright-field imaging with HIFU applied near the tissue surface, parameters derived from the spatiotemporal evolution of temperature were correlated with HIFU-induced lesion formation and overheating, of which the latter typically results in cavity generation and/or tissue dehydration. Emissivity of porcine myocardium was first measured to be 0.857 ± 0.006 (n = 3). HIFU outcomes were classified into non-ablative, normal lesion, and overheated lesion. A marked increase in the rate of temperature change during HIFU application was observed with lesion formation. A criterion using the maximum normalized second time derivative of temperature change provided 99.1% accuracy for lesion identification with a 0.05 s−1 threshold. Asymmetric temperature distribution on the tissue surface was observed to correlate with overheating and/or bubble generation. A criterion using the maximum displacement of the spatial location of the peak temperature provided 90.9% accuracy to identify overheated lesion with a 0.16 mm threshold. Spatiotemporal evolution of temperature obtained using IR imaging allowed determination of the cumulative equivalent minutes at 43 °C (CEM43) for lesion formation to be 170 min. Similar temperature characteristics indicative of lesion formation and overheating were identified for subsurface HIFU ablation. These results suggest that parameters derived from temperature changes during HIFU application are associated with irreversible changes in tissue and may provide useful

  14. Performance assessment of HIFU lesion detection by Harmonic Motion Imaging for Focused Ultrasound (HMIFU): A 3D finite-element-based framework with experimental validation

    PubMed Central

    Hou, Gary Y.; Luo, Jianwen; Marquet, Fabrice; Maleke, Caroline; Vappou, Jonathan; Konofagou, Elisa E.

    2014-01-01

    Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on Amplitude-modulated (AM) - Harmonic Motion Imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module, and an image-formation model. The objective of this study is to develop such a framework in order to 1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young's modulus, and the HIFU lesion size with respect to the HIFU exposure time and 2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young's modulus ratio of 3, 6, and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69, 5.39 and 1.65, 3.19, 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28, and 1.78 at 10-s, 20-s, and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was also found in both simulations (16.2, 73.1 and 334.7 mm2) and experiments (26.2, 94.2 and 206.2 mm2). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo. PMID:22036637

  15. Performance assessment of HIFU lesion detection by harmonic motion imaging for focused ultrasound (HMIFU): a 3-D finite-element-based framework with experimental validation.

    PubMed

    Hou, Gary Y; Luo, Jianwen; Marquet, Fabrice; Maleke, Caroline; Vappou, Jonathan; Konofagou, Elisa E

    2011-12-01

    Harmonic motion imaging for focused ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on amplitude-modulated (AM) - harmonic motion imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module and an image-formation model. The objective of this study is to develop such a framework to (1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young's modulus, and the HIFU lesion size with respect to the HIFU exposure time and (2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young's modulus ratio of 3, 6 and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69 and 5.39 and 1.65, 3.19 and 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28 and 1.78 at 10-s, 20-s and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was found in both simulations (16.2, 73.1 and 334.7 mm(2)) and experiments (26.2, 94.2 and 206.2 mm(2)). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo.

  16. Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity.

    PubMed

    van de Hoef, Tim P; Nolte, Froukje; Damman, Peter; Delewi, Ronak; Bax, Matthijs; Chamuleau, Steven A J; Voskuil, Michiel; Siebes, Maria; Tijssen, Jan G P; Spaan, Jos A E; Piek, Jan J; Meuwissen, Martijn

    2012-08-01

    The assessment of functional coronary lesion severity using intracoronary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice. A total of 232 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20-40 µg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of baseline SR (area under the curve, 0.77; 95% CI, 0.71-0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71-0.83 and area under the curve, 0.75; 95% CI, 0.68-0.81 respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76-0.87; P<0.05 compared with all other parameters). Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the

  17. The evaluation of intraarticular lesions accompanying ACL ruptures in military personnel who elected not to restrict their daily activities: the effect of age and time from injury.

    PubMed

    Yüksel, Halil Yalçin; Erkan, Serkan; Uzun, Macit

    2006-11-01

    The purpose of this study was to evaluate arthroscopically the type, localization and prevalence of the meniscal and chondral lesions accompanying complete rupture of the anterior cruciate ligament (ACL) in patients who elected not to restrict their daily activities after the initial trauma. The size of the chondral lesions was also evaluated. Our second aim is to analyze the effects of age, time from injury, and both age and time from injury in the presence or absence of accompanying lesions in these patients. The localization and type of the accompanying lesions of 317 knees with complete rupture of the ACL were recorded by the same observer. We applied therapeutic arthroscopy to all patients after their first visit to our clinic. All of the patients were military personnel and their history revealed that they had elected to not restrict their occupational activities after the first trauma causing ACL insufficiency. We defined the first 6 week period after the initial trauma as the acute, 6 weeks to 12 months as the subchronic and 12 months or longer as the chronic period. The average time from injury to arthroscopy for these patients, who were all male, was 19.4 +/- 20.3 months. Eighty-one percent of the patients had at least one meniscal tear, and 45.1% had at least one chondral lesion. The mean ages at the time of surgery of patient groups with or without medial and lateral menisci lesions were compared, and no statistically significant difference was determined. In the chronic period, the relative risk (RR) values of meniscal tears were 7.75 for medial and 2.40 for lateral. The group consisting of patients with chondral lesions was compared with the group of patients without chondral lesions in terms of their ages and the time from injury to arthroscopy, and the difference was statistically significant. The RR value for patients with co-existence of at least two lesions was 1.761 for more than 30 years of age. The RR values for at least two lesions were 2

  18. Assessment of FDG retention differences between the FDG-avid benign pulmonary lesion and primary lung cancer using dual-time-point FDG-PET imaging.

    PubMed

    Kaneko, Koichiro; Sadashima, Eiji; Sadashima, Shinji; Irie, Koji; Hayashi, Akihiro; Masunari, Satoru; Yoshida, Tsuyoshi; Omagari, Junichi

    2013-05-01

    The aim of this study was to clarify FDG retention differences between FDG-avid benign pulmonary lesions (BPLs) and primary lung cancers (PLCs), and between tuberculous and non-tuberculous BPLs using dual-time-point FDG-PET imaging. Thirty-four BPLs and 47 PLCs with a maximal standardized uptake value (SUVmax) >2.5 and a maximal axial diameter >10 mm were enrolled. We compared the retention index (RI) among different types of lesions, and evaluated the relationship between RI and SUVmax at 1 h (SUV1). Glucose transporter-1 (Glut-1) and hexokinase (HK)-2 expression was assessed in eight non-tuberculous BPLs. BPLs and PLCs showed similar high RIs (mean ± SD 33.6 ± 22.6 and 32.5 ± 23.7, respectively; p = 0.95). In BPLs, both tuberculous and non-tuberculous lesions showed high RIs (39.1 ± 25.8 and 30.3 ± 20.3, respectively; p = 0.43). However, BPLs and PLCs exhibited a different relationship between RI and SUV1. BPLs tended to show lower RIs with higher SUV1s, and a mild negative correlation, whereas PLCs showed persistent high RIs and no significant correlation. Glut-1 and HK-2 expression was found in 75 and 12.5 % of non-tuberculous BPLs, respectively. FDG-avid BPLs could show high RIs regardless of their being tuberculous and non-tuberculous lesions, and no significant difference with PLC RIs was found. FDG-avid BPLs and PLCs showed different relationships between RI and SUV1, and it seemed to be related with different mechanisms of high FDG retention. However, the mechanisms of high FDG retention in FDG-avid BPLs remain unclear, and this matter requires further investigation.

  19. Metabolic assessments during extra-vehicular activity

    NASA Astrophysics Data System (ADS)

    Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  20. Metabolic assessments during extra-vehicular activity.

    PubMed

    Osipov YuYu; Spichkov, A N; Filipenkov, S N

    1998-01-01

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha' (ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  1. Assessment of p53 protein expression in normal mucosa and benign and malignant lesions of the nasal cavity.

    PubMed

    Fang, S Y; Yan, J J; Ohyama, M

    1998-01-01

    p53 gene mutation is documented in head and neck cancer. No reports exist relating this mutation to normal mucosa or benign and malignant lesions of the nasal cavity. We investigate p53 overexpression using immunohistochemical techniques improved by an antigen retrieval method. p53 protein was analyzed in the following cases: normal, benign [papilloma and inverted papilloma (IP)] and malignant [squamous-cell carcinoma (SCC) arising in IP, SCC alone, adenocarcinoma and small-cell carcinoma]. Both the intensity and rate of positive p53 immunostaining were evaluated using a quantitative Auto-CAD program. Overexpression of p53 protein was not identified in normal mucosa, benign or premalignant lesions; however, approximately 60% is correlated to nasal cancer. p53 overexpression correlates with heavy smoking. Both the IP and SCC portions of SCC synchronous with IP showed similar p53 immunoreactivity. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Thus, smoking along with a p53 mutation may be a mutagenic agent in nasal cancers. Alteration of the p53 protein may play an important role in the early stages of the malignant transformation of IP. A low p53 immunoreactivity indicates the presence of wild-type p53 protein. This may show a better response to radiation therapy yielding a better prognosis for SCC arising in IP compared to SCC alone. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.

  2. Reliability of Peak Exercise Stroke Volume Assessment by Impedance Cardiography in Patients with Residual Right Outflow Tract Lesions After Congenital Heart Disease Repair.

    PubMed

    Legendre, Antoine; Bonnet, D; Bosquet, L

    2017-09-25

    Global ventricular response to exercise may be useful in follow-up of patients with residual right outflow tract lesions after congenital heart disease repair. In this context, impedance cardiography is considered accurate for stroke volume (SV) measurement during exercise testing, however, to date, only partial assessment of its reliability has been reported. We retrospectively evaluated relative and absolute reliability of peak SV by impedance cardiography during exercise using intraclass correlation (ICC) and standard error of measurement (SEM) in this population. Peak SV was measured in 30 young patients (mean age 14.4 years ± 2.1) with right ventricular outflow tract reconstruction who underwent two cardiopulmonary exercise tests at a mean one-year interval. SV was measured using a signal morphology impedance cardiography analysis device (PhysioFlow(®)) and was indexed to body surface area. ICC of peak indexed SV measurement was 0.80 and SEM was 10.5%. High heterogeneity was seen when comparing patients according to peak indexed SV; in patients with peak SV < 50 ml/m(2) (15 patients), ICC rose to 0.95 and SEM dropped to 2.7%, while in patients with a peak SV > 50 ml/m(2) relative and absolute reliability decreased (ICC = 0.45, SEM = 12.2%). Peak exercise SV assessment by a PhysioFlow(®) device represents a highly reliable method in patients with residual right outflow tract lesions after congenital heart disease repair, especially in patients with peak SV < 50 ml/m(2). In this latter group, a peak SV decrease > 7.3% (corresponding to the minimum "true" difference) should be considered a clinically-relevant decrease in global ventricular performance and taken into account when deciding whether to perform residual lesion removal.

  3. The Werner syndrome protein limits the error-prone 8-oxo-dG lesion bypass activity of human DNA polymerase kappa.

    PubMed

    Maddukuri, Leena; Ketkar, Amit; Eddy, Sarah; Zafar, Maroof K; Eoff, Robert L

    2014-10-29

    Human DNA polymerase kappa (hpol κ) is the only Y-family member to preferentially insert dAMP opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) during translesion DNA synthesis. We have studied the mechanism of action by which hpol κ activity is modulated by the Werner syndrome protein (WRN), a RecQ helicase known to influence repair of 8-oxo-dG. Here we show that WRN stimulates the 8-oxo-dG bypass activity of hpol κ in vitro by enhancing the correct base insertion opposite the lesion, as well as extension from dC:8-oxo-dG base pairs. Steady-state kinetic analysis reveals that WRN improves hpol κ-catalyzed dCMP insertion opposite 8-oxo-dG ∼10-fold and extension from dC:8-oxo-dG by 2.4-fold. Stimulation is primarily due to an increase in the rate constant for polymerization (kpol), as assessed by pre-steady-state kinetics, and it requires the RecQ C-terminal (RQC) domain. In support of the functional data, recombinant WRN and hpol κ were found to physically interact through the exo and RQC domains of WRN, and co-localization of WRN and hpol κ was observed in human cells treated with hydrogen peroxide. Thus, WRN limits the error-prone bypass of 8-oxo-dG by hpol κ, which could influence the sensitivity to oxidative damage that has previously been observed for Werner's syndrome cells.

  4. The Werner syndrome protein limits the error-prone 8-oxo-dG lesion bypass activity of human DNA polymerase kappa

    PubMed Central

    Maddukuri, Leena; Ketkar, Amit; Eddy, Sarah; Zafar, Maroof K.; Eoff, Robert L.

    2014-01-01

    Human DNA polymerase kappa (hpol κ) is the only Y-family member to preferentially insert dAMP opposite 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG) during translesion DNA synthesis. We have studied the mechanism of action by which hpol κ activity is modulated by the Werner syndrome protein (WRN), a RecQ helicase known to influence repair of 8-oxo-dG. Here we show that WRN stimulates the 8-oxo-dG bypass activity of hpol κ in vitro by enhancing the correct base insertion opposite the lesion, as well as extension from dC:8-oxo-dG base pairs. Steady-state kinetic analysis reveals that WRN improves hpol κ-catalyzed dCMP insertion opposite 8-oxo-dG ∼10-fold and extension from dC:8-oxo-dG by 2.4-fold. Stimulation is primarily due to an increase in the rate constant for polymerization (kpol), as assessed by pre-steady-state kinetics, and it requires the RecQ C-terminal (RQC) domain. In support of the functional data, recombinant WRN and hpol κ were found to physically interact through the exo and RQC domains of WRN, and co-localization of WRN and hpol κ was observed in human cells treated with hydrogen peroxide. Thus, WRN limits the error-prone bypass of 8-oxo-dG by hpol κ, which could influence the sensitivity to oxidative damage that has previously been observed for Werner's syndrome cells. PMID:25294835

  5. Simulations as Active Assessment?: Typologizing by Purpose and Source

    ERIC Educational Resources Information Center

    Kollars, Nina A.; Rosen, Amanda M.

    2013-01-01

    Assessment through simulation is something that political science pedagogy has yet to explore in a robust manner. This article advances analysis of social science simulation and assessment by laying out a typology of active-learning activities that isolates and examines their potential for assessment. In short, we argue that there are essentially…

  6. Simulations as Active Assessment?: Typologizing by Purpose and Source

    ERIC Educational Resources Information Center

    Kollars, Nina A.; Rosen, Amanda M.

    2013-01-01

    Assessment through simulation is something that political science pedagogy has yet to explore in a robust manner. This article advances analysis of social science simulation and assessment by laying out a typology of active-learning activities that isolates and examines their potential for assessment. In short, we argue that there are essentially…

  7. Diagnostic yield of ink-jet prints from digital radiographs for the assessment of approximal carious lesions: ROC-analysis.

    PubMed

    Schulze, Ralf K W; Grimm, Stefanie; Schulze, Dirk; Voss, Kai; Keller, Hans-Peter; Wedel, Matthias

    2011-08-01

    To investigate the diagnostic quality of different quality, individually calibrated ink-jet printers for the very challenging dental radiographic task of approximal carious lesion detection. A test-pattern evaluating resolution, contrast and homogeneity of the ink-jet prints was developed. 50 standardized dental radiographs each showing two neighbouring teeth in natural contact were printed on glossy paper with calibrated, randomly selected ink-jet printers (Canon S520 and iP4500, Epson Stylus Photo R2400). Printing size equalled the viewing size on a 17″ cathode-ray-tube monitor daily quality-tested according to German regulations. The true caries status was determined from serial sectioning and microscopic evaluation. 16 experienced observers evaluated the radiographs on a five-point confidence scale on all prints plus the viewing monitor with respect to the visibility of a carious lesion. A non-parametric Receiver-Operating Characteristics (ROC-) analysis was performed explicitly designed for the evaluation of readings stemming from identical samples but different modality. Significant differences are expressed by a critical ratio z exceeding ±2. Diagnostic accuracy was determined by the area (Az) underneath the ROC-curves. Average Az-values ranged between 0.62 (S520 and R2400) and 0.64 (monitor, iP4500), with no significant difference between modalities (P=0.172). Neither significant (range mean z: -0.40 (S520) and -0.11 (iP4500)) nor clinically relevant differences were found between printers and viewing monitor. Our results for a challenging task in dental radiography indicate that calibrated, off-the-shelf ink-jet printers are able to reproduce (dental) radiographs at quality levels sufficient for radiographic diagnosis in a typical dental working environment. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from the Kuwait oil fires

    SciTech Connect

    Moeller, R.B. Jr.; Dick, E.J.; Pletcher, J.M.

    1994-12-31

    Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively smoke-free area, and 14 from the city of Ahmadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Tracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined. 36 refs., 3 figs., 7 tabs.

  9. Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from Kuwait oil fires

    SciTech Connect

    Moeller, R.B.; Kalasinsky, V.F.; Razzaque, M.; Centeno, J.A.; Dick, E.J.

    1994-12-31

    Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively Co smoke-free area, and 14 from the city of Alimadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all 0 major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Iracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems (a) were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined.

  10. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

    PubMed Central

    Azevedo, Michelle de C. S.; Rosa, Patricia S.; Soares, Cleverson T.; Fachin, Luciana R. V.; Baptista, Ida Maria F. D.; Woods, William J.; Garlet, Gustavo P.

    2015-01-01

    Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  11. Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

    PubMed

    Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

    2017-12-01

    Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-i