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Sample records for total lesion glycolysis

  1. Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib

    International Nuclear Information System (INIS)

    Lim, Yoojoo; Lee, Kyung-Hun; Bang, Ji-In; Paeng, Jin Chul; Han, Sae-Won; Kim, Jee Hyun; Kang, Gyeong Hoon; Jeong, Seung-Yong; Park, Kyu Joo; Kim, Tae-You

    2017-01-01

    This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC). Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome. A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG 40 % ). Further analysis using TLG 40 % showed significantly longer overall survival (OS) in patients with lower baseline TLG 40 % (<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG 40 % after treatment showed significantly longer progression-free survival (PFS) (p = 0.001, median 8.0 vs. 2.4 months in % ΔTLG 40 % < -9.6 % and ≥ -9.6 %, respectively) and OS (p = 0.002, median 16.4 vs. 9.1 months in % ΔTLG 40 % < -9.6 % and ≥ -9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5 months, p = 0.049). Measurement of TLG can predict treatment outcome of regorafenib in mCRC. (orig.)

  2. Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yoojoo; Lee, Kyung-Hun [Seoul National University Hospital, Department of Internal Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Bang, Ji-In; Paeng, Jin Chul [Seoul National University Hospital, Department of Nuclear Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Han, Sae-Won [Seoul National University Hospital, Department of Internal Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Kim, Jee Hyun [Seoul National University Bundang Hospital, Department of Internal Medicine, Geyonggi-do (Korea, Republic of); Kang, Gyeong Hoon [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Jeong, Seung-Yong; Park, Kyu Joo [Seoul National University Hospital, Department of Surgery, Seoul (Korea, Republic of); Kim, Tae-You [Seoul National University Hospital, Department of Internal Medicine, 101 Daehang-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of)

    2017-05-15

    This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC). Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome. A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG{sub 40} {sub %}). Further analysis using TLG{sub 40} {sub %} showed significantly longer overall survival (OS) in patients with lower baseline TLG{sub 40} {sub %} (<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG{sub 40} {sub %} after treatment showed significantly longer progression-free survival (PFS) (p = 0.001, median 8.0 vs. 2.4 months in % ΔTLG{sub 40} {sub %} < -9.6 % and ≥ -9.6 %, respectively) and OS (p = 0.002, median 16.4 vs. 9.1 months in % ΔTLG{sub 40} {sub %} < -9.6 % and ≥ -9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5 months, p = 0.049). Measurement of TLG can predict treatment outcome of regorafenib in mCRC. (orig.)

  3. Total Lesion Glycolysis and Sequential (90)Y-Selective Internal Radiation Therapy in Breast Cancer Liver Metastases: Preliminary Results.

    Science.gov (United States)

    Bagni, Oreste; Filippi, Luca; Pelle, Giuseppe; Cianni, Roberto; Schillaci, Orazio

    2015-12-01

    To assess the prognostic role of total lesion glycolysis (TLG) in patients with breast cancer liver metastases (BCLM) after sequential lobar (90)Y-radioembolization ((90)Y-RE). Seventeen patients with bilobar BCLM underwent FDG PET/CT and TLG calculation before (90)Y-RE. The hepatic lobe with the highest TLG was treated in the first session. PET was performed 6 weeks postprocedure and decrease in TLG (ΔTLG) in the treated lobe was calculated before the second (90)Y administration. Subjects were divided in two groups (group 1: ΔTLG >50%, group 2: ΔTLG 50% and seven had a ΔTLG value 50% and ΔTLG <50% had a mean OS of 16.4 ± 0.6 and 10.3 ± 0.4 months, respectively (p < 0.001). Cox regression analysis demonstrated hepatic tumor load (p = 0.048) and ΔTLG as the only significant (p = 0.005) predictors of survival. ΔTLG after the first (90)Y administration agrees with final outcome in BCLM patients after separate sequential lobar (90)Y-RE.

  4. Diagnostic importance of 18F-FDG PET/CT parameters and total lesion glycolysis in differentiating between benign and malignant adrenal lesions.

    Science.gov (United States)

    Ciftci, Esra; Turgut, Bulent; Cakmakcilar, Ali; Erturk, Seyit A

    2017-09-01

    Benign adrenal lesions are prevalent in oncologic imaging and make metastatic disease diagnoses difficult. This study evaluates the diagnostic importance of metabolic, volumetric, and metabolovolumetric parameters measured by fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in differentiating between benign and malignant adrenal lesions in cancer patients. In this retrospective study, we evaluated F-FDG PET/CT parameters of adrenal lesions of follow-up cancer patients referred to our clinic between January 2012 and November 2016. The diagnosis of adrenal malignant lesions was made on the basis of interval growth or reduction after chemotherapy. Patient demographics, analysis of metabolic parameters such as maximum standard uptake value (SUVmax), tumor SUVmax/liver SUVmean ratio (T/LR), morphologic parameters such as size, Hounsfield Units, and computed tomography (CT) volume, and metabolovolumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) of adrenal lesions were calculated. PET/CT parameters were assessed using the Mann-Whitney U-test and receiving operating characteristic analysis. In total, 186 adrenal lesions in 163 cancer patients (108 men/54 women; mean±SD age: 64±10.9 years) were subjected to F-FDG PET/CT for tumor evaluation. SUVmax values (mean±SD) were 2.8±0.8 and 10.6±6; TLG were 10.8±9.2 and 124.4±347.9; and T/LR were 1±0.3 and 4.1±2.6 in benign and malignant adrenal lesions, respectively. On the basis of the area under the curve, adrenal lesion SUVmax and T/LR had similar highest diagnostic performance for predicting malignant lesions (area under the curve: 0.993 and 0.991, respectively, P<0.001). Multivariate logistic regression analysis showed that T/LR, adrenal lesion SUVmax, and Hounsfield Units were independent predictive factors for malignancy rather than TLG. Irrespective of whether TLG was statistically highly significant for differentiating benign from malignant adrenal lesions, it did not reach the

  5. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

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    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  6. Prognostic value of total lesion glycolysis on preoperative {sup 18}F-FDG PET/CT in patients with uterine carcinosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong-Won [Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Sungkyunkwan University School of Medicine, Samsung Advanced Institute for Health Sciences and Technology, Seoul (Korea, Republic of); Heo, Eun Jin [Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Moon, Seung Hwan [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of)

    2016-11-15

    To investigate the relationship between functional tumour parameters measured during preoperative {sup 18}F-FDG PET/CT and clinical outcomes in patients with uterine carcinosarcoma. For patients with pathologically proven uterine carcinosarcoma, we determined the maximal and average standardized uptake values, cumulative total lesion glycolysis (TLG) and sum of all metabolic tumour volumes (MTVs). Their predictive value for recurrence and the effects of pretreatment functional tumour activity on patient survival were compared. Clinicopathological data from 28 eligible patients were reviewed. The median duration of progression-free survival was 18.6 months (range 6.1-84.5 months), and 10 (35.7 %) patients experienced recurrences. Univariate analyses showed significant associations between recurrence and tumour size, lymph node metastasis, high TLG and MTV values, and ovarian invasion. Multivariate analysis identified high TLG value as an independent risk factor for recurrence (p = 0.048, hazard ratio 115.261, 95 % confidence interval 1.041-12,765.483). Kaplan-Meier survival curves showed that progression-free survival significantly differed in groups categorized according to TLG (p = 0.007, log-rank test). Preoperative TLG measured with {sup 18}F-FDG PET/CT was statistically significantly associated with uterine carcinosarcoma recurrence. Metabolic parameters can provide useful quantitative criteria for disease prognostication in patients with uterine carcinosarcoma before treatment. (orig.)

  7. Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging.

    Science.gov (United States)

    Jiménez-Ballvé, A; García García-Esquinas, M; Salsidua-Arroyo, O; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Fuentes Ferrer, M E; Rodríguez Rey, C; Román-Santamaría, J M; Moreno, F; Carreras-Delgado, J L

    To determine whether metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are able to predict recurrence risk in locally advanced breast cancer (LABC) patients. Retrospective study of LABC patients who undertook neoadjuvant, local and adjuvant treatment and follow up. A 18 F-FDG PET/CT study for initial staging was performed analysing in this study different metabolic parameters (MTV, TLG, SUVmax and SUVmed) both in the primary tumour (T) as well as in axillary nodes (N) and whole-body (WB). Forty females were included between January 2010-2011; follow up until January 2015 was completed. The average follow-up was 46 months. Twenty percent presented recurrence: local disease (n=2) and distant metastasis (n=6); 3 patients died (38% of the patients which recurred and 7.5% from the total). SUVmax, MTV and TLG, in T, N and WB, were higher in those patients with recurrence. The MTV and TLG parameters in the tumour (T) were related to the recurrence rate (P=.020 and P=.028, respectively); whereas SUVmax in the lymph nodes (N) was significantly related (P=.008) to the recurrence rate. The best cut-off points to predict recurrence where: MTV T ≥19.3cm 3 , TLG T≥74.4g and SUVmax N≥13.8, being 10-12 times more likely to recidivate when these thresholds where exceeded. Tumour grade was the only clinical-pathological variable which was related to recurrence probability (p=.035). In this study of LABC patients the metabolic parameters which have a better relationship with recurrence rate are: MTV and TLG in the primary tumour, SUVmax in the regional lymph node disease and whole-body PET data. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  8. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

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    Dholakia, Avani S. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chaudhry, Muhammad; Leal, Jeffrey P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chang, Daniel T. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Raman, Siva P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Su, Zheng; Pai, Jonathan [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Oteiza, Katharine E.; Griffith, Mary E. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wahl, Richard L. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pawlik, Timothy [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Laheru, Daniel A. [Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wolfgang, Christopher L. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); and others

    2014-07-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in

  9. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Dholakia, Avani S.; Chaudhry, Muhammad; Leal, Jeffrey P.; Chang, Daniel T.; Raman, Siva P.; Hacker-Prietz, Amy; Su, Zheng; Pai, Jonathan; Oteiza, Katharine E.; Griffith, Mary E.; Wahl, Richard L.; Tryggestad, Erik; Pawlik, Timothy; Laheru, Daniel A.; Wolfgang, Christopher L.; Koong, Albert C.

    2014-01-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV max and SUV peak ) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver mean + [2 × Liver sd ]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm 3 or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy

  10. PET quantification with a histogram derived total activity metric: Superior quantitative consistency compared to total lesion glycolysis with absolute or relative SUV thresholds in phantoms and lung cancer patients

    International Nuclear Information System (INIS)

    Burger, Irene A.; Vargas, Hebert Alberto; Apte, Aditya; Beattie, Bradley J.; Humm, John L.; Gonen, Mithat; Larson, Steven M.; Ross Schmidtlein, C.

    2014-01-01

    Introduction: The increasing use of molecular imaging probes as biomarkers in oncology emphasizes the need for robust and stable methods for quantifying tracer uptake in PET imaging. The primary motivation for this research was to find an accurate method to quantify the total tumor uptake. Therefore we developed a histogram-based method to calculate the background subtracted lesion (BSL) activity and validated BSL by comparing the quantitative consistency with the total lesion glycolysis (TLG) in phantom and patient studies. Methods: A thorax phantom and a PET-ACR quality assurance phantom were scanned with increasing FDG concentrations. Volumes of interest (VOIs) were placed over each chamber. TLG was calculated with a fixed threshold at SUV 2.5 (TLG 2.5 ) and a relative threshold at 42% of SUV max (TLG 42% ). The histogram for each VOI was built and BSL was calculated. Comparison with the total injected FDG activity (TIA) was performed using concordance correlation coefficients (CCC) and the slope (a). Fifty consecutive patients with FDG-avid lung tumors were selected under an IRB waiver. TLG 42% , TLG 2.5 and BSL were compared to the reference standard calculating CCC and the slope. Results: In both phantoms, the CCC for lesions with a TIA ≤ 50 ml*SUV between TIA and BSL was higher and the slope closer to 1 (CCC = 0.933, a = 1.189), than for TLG 42% (CCC = 0.350, a = 0.731) or TLG 2.5 (CCC = 0.761, a = 0.727). In 50 lung lesions BSL had a slope closer to 1 compared to the reference activity than TLG 42% (a = 1.084 vs 0.618 – for high activity lesions) and also closer to 1 than TLG 2.5 (a = 1.117 vs 0.548 – for low activity lesions). Conclusion: The histogram based BSL correlated better with TIA in both phantom studies than TLG 2.5 or TLG 42% . Also in lung tumors, the BSL activity is overall more accurate in quantifying the lesion activity compared to the two most commonly applied TLG quantification methods

  11. Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on {sup 18}F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma

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    Kim, Choon-Young; Hong, Chae Moon; Kim, Do-Hoon; Son, Seung Hyun; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol [Kyungpook National University School of Medicine and Hospital, Department of Nuclear Medicine, Daegu (Korea, Republic of)

    2013-09-15

    The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment {sup 18}F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment {sup 18}F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV > 3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG). During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm{sup 3} and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS. Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes. (orig.)

  12. Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by {sup 18}F-FDG PET/CT in squamous cell carcinoma of the oral cavity

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    Ryu, In Sun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Cho, Kyung-Ja [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of); Kim, Sang Yoon [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Center, Seoul (Korea, Republic of); Biomedical Research Institute, Korean Institute of Science and Technology, Seoul (Korea, Republic of)

    2014-03-15

    Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from {sup 18}F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by {sup 18}F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Of 162 patients with OSCC evaluated preoperatively by {sup 18}F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUV{sub max}), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). The median (range) SUV{sub max}, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS. Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC. (orig.)

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

    Science.gov (United States)

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

    2016-11-15

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

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

    Science.gov (United States)

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

    2016-01-01

    Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered. To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH. The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival. These findings open perspectives for novel targeted therapies in pancreatic cancer. PMID:27494892

  15. The cyclops lesion after bicruciate-retaining total knee replacement

    Directory of Open Access Journals (Sweden)

    Mark A. Klaassen, MD, FACS

    2017-12-01

    Full Text Available The cyclops lesion is a localized anterior arthrofibrosis most commonly seen following anterior cruciate ligament reconstruction. The lesion forms at the anterior cruciate ligament insertion creating a painful extension block between femoral intercondylar notch and tibial plateau. We present 2 cases (3 knees in which cyclops lesions appeared atypically following bicruciate-retaining total knee replacement. Two lesions occurred in a single patient following bilateral knee replacement. One lesion occurred in an active sportswoman. All 3 resolved following arthroscopic debridement. We describe the presentation of this unusual complication and suggest keys to its diagnosis, treatment, and prevention. Keywords: Cyclops lesion, Bicruciate-retaining, Total knee arthroplasty, Extension deficit

  16. The cyclops lesion after bicruciate-retaining total knee replacement

    OpenAIRE

    Klaassen, Mark A.; Aikins, Jerry L.

    2017-01-01

    The cyclops lesion is a localized anterior arthrofibrosis most commonly seen following anterior cruciate ligament reconstruction. The lesion forms at the anterior cruciate ligament insertion creating a painful extension block between femoral intercondylar notch and tibial plateau. We present 2 cases (3 knees) in which cyclops lesions appeared atypically following bicruciate-retaining total knee replacement. Two lesions occurred in a single patient following bilateral knee replacement. One les...

  17. Prótesis totales y lesiones bucales en adultos mayores institucionalizados Total Prosthetics and Oral Lesions in Institutionalized Elderly

    Directory of Open Access Journals (Sweden)

    Beatriz García Alpízar

    2012-03-01

    Full Text Available Fundamento: las prótesis dentales constituyen una alternativa al perderse los dientes, pero no están exentas de provocar daños, que junto a la susceptibilidad de los tejidos, provocada por el envejecimiento e inadecuados estilos de vida, pueden llevar a la aparición de lesiones bucales. Objetivo: describir las características de pacientes portadores de prótesis totales y su relación con las lesiones bucales. Métodos: estudio descriptivo, con 93 ancianos institucionalizados portadores de prótesis total. Se utilizaron las pruebas de chi cuadrado y el riesgo relativo para determinar la asociación entre las variables: edad, sexo, higiene, estado de conservación, tiempo y frecuencia de uso de la prótesis, necesidades de prótesis, tipo de lesión, localización, hábito de fumar, enfermedades sistémicas y medicamentos empleados. Resultados: el 78,5 % de los ancianos presentó lesiones relacionadas con el uso de la prótesis. La estomatitis subprótesis fue la lesión más frecuente. La presencia de lesiones bucales fue significativa en aquellos con 80 años y más (100 %. El 95,8 % tenían prótesis deterioradas, y en la totalidad de ellos, las prótesis tenían 21 años y más de uso. El riesgo de desarrollar lesiones fue 2,98 veces superior en aquellos con una higiene bucal deficiente. El 100 % de los ancianos diabéticos y anémicos presentaron lesiones. Conclusiones: las lesiones bucales estuvieron muy relacionadas con los factores locales: estado de conservación, higiene, tiempo de uso de las prótesis; y con factores generales como: incremento de la edad, enfermedades sistémicas y uso de medicamentos para su tratamiento.Background: Prosthetics or dentures are an alternative to missing teeth. Nevertheless, they carry the risk of producing certain damage that, along with the susceptibility of the tissues caused by aging and inadequate lifestyles, can lead to the development of oral lesions. Objective: To describe the

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

    Science.gov (United States)

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

    2012-11-01

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

  19. Prótesis totales y lesiones bucales en adultos mayores institucionalizados

    Directory of Open Access Journals (Sweden)

    Beatriz García Alpízar

    2012-03-01

    Full Text Available Fundamento: las prótesis dentales constituyen una alternativa al perderse los dientes, pero no están exentas de provocar daños, que junto a la susceptibilidad de los tejidos, provocada por el envejecimiento e inadecuados estilos de vida, pueden llevar a la aparición de lesiones bucales. Objetivo: describir las características de pacientes portadores de prótesis totales y su relación con las lesiones bucales. Métodos: estudio descriptivo, con 93 ancianos institucionalizados portadores de prótesis total. Se utilizaron las pruebas de chi cuadrado y el riesgo relativo para determinar la asociación entre las variables: edad, sexo, higiene, estado de conservación, tiempo y frecuencia de uso de la prótesis, necesidades de prótesis, tipo de lesión, localización, hábito de fumar, enfermedades sistémicas y medicamentos empleados. Resultados: el 78,5 % de los ancianos presentó lesiones relacionadas con el uso de la prótesis. La estomatitis subprótesis fue la lesión más frecuente. La presencia de lesiones bucales fue significativa en aquellos con 80 años y más (100 %. El 95,8 % tenían prótesis deterioradas, y en la totalidad de ellos, las prótesis tenían 21 años y más de uso. El riesgo de desarrollar lesiones fue 2,98 veces superior en aquellos con una higiene bucal deficiente. El 100 % de los ancianos diabéticos y anémicos presentaron lesiones. Conclusiones: las lesiones bucales estuvieron muy relacionadas con los factores locales: estado de conservación, higiene, tiempo de uso de las prótesis; y con factores generales como: incremento de la edad, enfermedades sistémicas y uso de medicamentos para su tratamiento.

  20. Outcomes of the Endovascular Treatment of Stenotic Lesions versus Chronic Total Occlusions in the Iliac Sector.

    Science.gov (United States)

    Revuelta Suero, Sergio; Martínez López, Isaac; Hernández Mateo, Manuela; Marqués de Marino, Pablo; Cernuda Artero, Iñaki; Cabrero Fernández, Maday; Serrano Hernando, Francisco Javier

    2016-07-01

    This study compares outcomes of the endovascular treatment (EVT) of iliac artery occlusive disease according to whether the treated lesion is a stenosis or a chronic total occlusion (CTO). Patients undergoing EVT from 2003 to 2013 for iliac artery occlusive disease were identified and the lesions treated stratified into stenotic (Group 1, n = 375) or CTO (Group 2, n = 87). Patients were followed clinically and hemodynamically (thigh-brachial index, TBI). Comorbidities, procedural factors, and outcomes were compared between the 2 groups using Kaplan-Meier, Breslow, and Cox models. Four hundred sixty-two iliac endovascular procedures in 378 patients were included in a retrospective study. The 2 groups only differed in preprocedural TBI [0.77 (Group 1) vs. 0.67 (Group 2), P P2) patency rates [P1 93.0% and 85.8% vs. 83.1% and 74.7%, hazard ratio (HR) 1.90 (1.15-3.14), P = 0.018; P2 97.8% and 96.8% vs. 93.0% and 87.4%, HR 2.86 (1.39-5.90), P = 0.007] and freedom from reintervention (FFR) rates [91.6% and 83.5% vs. 84.1% and 78.9%, HR 1.51 (0.90-2.53), P = 0.132]. In a multivariate analysis, CTO showed a worse P2 than stenotic lesions [HR 2.81 (1.17-6.76), P = 0.021], yet no differences emerged in P1 [HR 1.41 (0.76-2.63), P = 0.277] or FFR [HR 1.43 (0.79-2.57), P = 0.237]. A lower preprocedural TBI was correlated with a greater risk of EVT failure in terms of patency and FFR (P 40 mm were related to a worse stent patency. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan

    2012-10-01

    Full Text Available Abstract Serum lactate dehydrogenase (LDH is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS, we subsequently determined using tissue microarray (TMA analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.

  2. Elemental concentration in normal skin and fibroepithelial polip lesions by synchrotron radiation total reflection X-ray fluorescence technique

    International Nuclear Information System (INIS)

    Soares, Julio C.A.C.R.; Canellas, Catarine G.L.; Lopes, Ricardo T.; Anjos, Marcelino J.

    2011-01-01

    In this work, the concentrations of trace elements were measured in acrochordon, a skin lesion also known as skin tag or fibroepithelial polyp, as well as in normal skin from the same patient. The samples were analysed by Synchrotron Radiation Total Reflection X- ray Fluorescence (SRTXRF) in the Synchrotron Light National Laboratory (LNLS) in Campinas/Sao Paulo-Brazil. The collection of lesion and healthy skin samples, including papillary dermis and epidermis, has involved 17 patients. It was evaluated the presence of P, S, Cl, K, Ca, Cr, Mn, Fe, Cu, Zn, Br and Rb in the paired samples, which were compared, and significant differences were found in some of them. (author)

  3. Methylglyoxal, the dark side of glycolysis

    KAUST Repository

    Allaman, Igor; Bé langer, Mireille; Magistretti, Pierre J.

    2015-01-01

    Glucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity

  4. Radiation exposure to patient's skin during percutaneous coronary intervention for various lesions, including chronic total occlusion

    International Nuclear Information System (INIS)

    Suzuki, Shigeru; Furui, Shigeru; Kohtake, Hiroshi; Yokoyama, Naoyuki; Kozuma, Ken; Yamamoto, Yoshito; Isshiki, Takaaki

    2006-01-01

    Radiation skin injuries have been reported as a result of various procedures, so in the present study the patients' entrance skin dose (ESD) during percutaneous coronary intervention (PCI) was evaluated. ESDs were assessed during 97 procedures (13 for chronic total occlusion (CTO), 14 for multivessel stenoses, 22 for single-vessel multiple stenoses, and 48 for single stenosis). The patients wore jackets that had 48 or 52 radiosensitive indicators placed on the back during the PCI procedures, with 8 other indicators placed on both upper arms. After the procedure, the color of the indicators was analyzed with a color measuring instrument, and the patients' ESDs were calculated from the color difference of the indicators. The average maximum ESDs of the patients were 4.5±2.8 Gy (median: 4.6 Gy) for CTO, 2.3±0.7 Gy (median: 2.4 Gy) for multi-vessel stenoses, 1.8±1.0 Gy (median: 1.5 Gy) for single-vessel multiple stenoses, and 1.4±0.9 Gy (median: 1.2 Gy) for single stenosis. Skin injury can occur during PCI, especially for CTO, so it is important to estimate each patient's ESD and attempt to reduce it. (author)

  5. The success of opening single chronic total occlusion lesions to improve myocardialviabilitytrial (SOS-COMEDY)

    Science.gov (United States)

    Huang, Rongchong; Song, Xiantao; Zhang, Haishan; Tian, Wen; Huang, Zheng; Zhang, Xingwei; Yang, Junqing; Zhang, Dongfeng; Wu, Jian; Zhong, Lei; Ting, Henry H.

    2018-01-01

    Abstract Aims: Success of opening single (SOS)-comedy is a prospective multicenter study to compare the improvement in the decrease of myocardial viability by percutaneous coronary intervention (PCI) with that by optimal medical therapy (OMT) alone in patients with chronic total occlusion (CTO) of a single coronary artery. Methods and results: The risks and the benefits of both options (PCI and OMT) were listed in a CTO decision aid (DA). Eligible participants detected by invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) were divided into PCI or OMT groups according to patients’ choice after shared-decision making process with DA. Participants will undergo positron emission tomography/computed tomography (PET/CT), cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE), and proceed to ICA and revascularization if possible. Blinded core laboratory interpretation will be performed for ICA, CCTA, PET/CT, CMR, and TTE. All participants will be followed up for 12 months. The primary endpoint is the improvement to the decrease of myocardial viability from baseline assessed with the use of PET/CT after 12-month follow-up. Conclusions: All of the patients are appropriately consented before enrolling in this study, which has been approved by the Ethics Committee. Results of SOS-COMEDY will be helpful to develop a strategy for single CTO patients. PMID:29668609

  6. Oscillations in glycolysis in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Kloster, Antonina; Olsen, Lars Folke

    2012-01-01

    also decreases by stimulating the ATPase activity, e.g. by FCCP or Amphotericin B. Thus, ATPase activity strongly affects the glycolytic oscillations. We discuss these data in relation to a simple autocatalytic model of glycolysis which can reproduce the experimental data and explain the role...... of membrane-bound ATPases . In addition we also studied a recent detailed model of glycolysis and found that, although thismodel faithfully reproduces the oscillations of glycolytic intermediates observed experimentally, it is not able to explain the role of ATPase activity on the oscillations....

  7. Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis

    Directory of Open Access Journals (Sweden)

    Qiong Li

    2017-06-01

    Full Text Available Objective The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. Methods A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR, a specific activator of AMPK, AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases. After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. Results Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates. Conclusion Protein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated.

  8. Long-Term Primary Patency Rate After Nitinol Self-Expandable Stents Implantation in Long, Totally Occluded Femoropopliteal (TASC II C & D) Lesions.

    Science.gov (United States)

    Elmahdy, Mahmoud Farouk; Buonamici, Piergiovanni; Trapani, Maurizio; Valenti, Renato; Migliorini, Angela; Parodi, Guido; Antoniucci, David

    2017-06-01

    Endovascular therapy for long femoropopliteal lesions using percutaneous transluminal balloon angioplasty or first-generation of peripheral stents has been associated with unacceptable one-year restenosis rates. However, with recent advances in equipment and techniques, a better primary patency rate is expected. This study was conducted to detect the long-term primary patency rate of nitinol self-expandable stents implanted in long, totally occluded femoropopliteal lesions TransAtlantic Inter-Society Census (TASC II type C & D), and determine the predictors of reocclusion or restenosis in the stented segments. The demographics, clinical, anatomical, and procedural data of 213 patients with 240 de novo totally occluded femoropopliteal (TASC II type C & D) lesions treated with nitinol self-expandable stents were retrospectively analysed. Of these limbs, 159 (66.2%) presented with intermittent claudication, while 81 (33.8%) presented with critical limb ischaemia. The mean-time of follow-up was 36±22.6 months, (range: 6.3-106.2 months). Outcomes evaluated were, primary patency rate and predictors of reocclusion or restenosis in the stented segments. The mean age of the patients was 70.9±9.3 years, with male gender 66.2%. Mean pre-procedural ABI was 0.45±0.53. One-hundred-and-seventy-five (73%) lesions were TASC II type C, while 65 (27%) were type D lesions. The mean length of the lesions was 17.9±11.3mm. Procedure related complications occurred in 10 (4.1%) limbs. There was no periprocedural mortality. Reocclusion and restenosis were detected during follow-up in 45 and 30 limbs respectively, and all were re-treated by endovascular approach. None of the patients required major amputation. Primary patency rates were 81.4±1.1%, 77.7±1.9% and 74.4±2.8% at 12, 24, and 36 months respectively. Male gender, severe calcification, and TASC II D lesion were independent predictors for reocclusion, while predictors of restenosis were DM, smoking and TASC II D lesions

  9. Mangiferin Accelerates Glycolysis and Enhances Mitochondrial Bioenergetics

    Directory of Open Access Journals (Sweden)

    Zhongbo Liu

    2018-01-01

    Full Text Available One of the main causes of hyperglycemia is inefficient or impaired glucose utilization by skeletal muscle, which can be exacerbated by chronic high caloric intake. Previously, we identified a natural compound, mangiferin (MGF that improved glucose utilization in high fat diet (HFD-induced insulin resistant mice. To further identify the molecular mechanisms of MGF action on glucose metabolism, we conducted targeted metabolomics and transcriptomics studies of glycolyic and mitochondrial bioenergetics pathways in skeletal muscle. These data revealed that MGF increased glycolytic metabolites that were further augmented as glycolysis proceeded from the early to the late steps. Consistent with an MGF-stimulation of glycolytic flux there was a concomitant increase in the expression of enzymes catalyzing glycolysis. MGF also increased important metabolites in the tricarboxylic acid (TCA cycle, such as α-ketoglutarate and fumarate. Interestingly however, there was a reduction in succinate, a metabolite that also feeds into the electron transport chain to produce energy. MGF increased succinate clearance by enhancing the expression and activity of succinate dehydrogenase, leading to increased ATP production. At the transcriptional level, MGF induced mRNAs of mitochondrial genes and their transcriptional factors. Together, these data suggest that MGF upregulates mitochondrial oxidative capacity that likely drives the acceleration of glycolysis flux.

  10. 1H-MRS evaluation of breast lesions by using total choline signal-to-noise ratio as an indicator of malignancy: a meta-analysis.

    Science.gov (United States)

    Wang, Xin; Wang, Xiang Jiang; Song, Hui Sheng; Chen, Long Hua

    2015-05-01

    The aim of this study was to evaluate the diagnostic performance of the use of total choline signal-to-noise ratio (tCho SNR) criteria in MRS studies for benign/malignant discrimination of focal breast lesions. We conducted (1) a meta-analysis based on 10 studies including 480 malignant breast lesions and 312 benign breast lesions and (2) a subgroup meta-analysis of tCho SNR ≥ 2 as cutoff for malignancy based on 7 studies including 371 malignant breast lesions and 239 benign breast lesions. (1) The pooled sensitivity and specificity of proton MRS with tCho SNR were 0.74 (95 % CI 0.69-0.77) and 0.76 (95 % CI 0.71-0.81), respectively. The PLR and NLR were 3.67 (95 % CI 2.30-5.83) and 0.25 (95 % CI 0.14-0.42), respectively. From the fitted SROC, the AUC and Q* index were 0.89 and 0.82. Publication bias was present (t = 2.46, P = 0.039). (2) Meta-regression analysis suggested that neither threshold effect nor evaluated covariates including strength of field, pulse sequence, TR and TE were sources of heterogeneity (all P value >0.05). (3) Subgroup meta-analysis: The pooled sensitivity and specificity were 0.79 and 0.72, respectively. The PLR and NLR were 3.49 and 0.20, respectively. The AUC and Q* index were 0.92 and 0.85. The use of tCho SNR criteria in MRS studies was helpful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated due to publication bias. A tCho SNR ≥ 2 as cutoff for malignancy resulted in higher diagnostic accuracy.

  11. Glycolysis-respiration relationships in a neuroblastoma cell line.

    Science.gov (United States)

    Swerdlow, Russell H; E, Lezi; Aires, Daniel; Lu, Jianghua

    2013-04-01

    Although some reciprocal glycolysis-respiration relationships are well recognized, the relationship between reduced glycolysis flux and mitochondrial respiration has not been critically characterized. We concomitantly measured the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of SH-SY5Y neuroblastoma cells under free and restricted glycolysis flux conditions. Under conditions of fixed energy demand ECAR and OCR values showed a reciprocal relationship. In addition to observing an expected Crabtree effect in which increasing glucose availability raised the ECAR and reduced the OCR, a novel reciprocal relationship was documented in which reducing the ECAR via glucose deprivation or glycolysis inhibition increased the OCR. Substituting galactose for glucose, which reduces net glycolysis ATP yield without blocking glycolysis flux, similarly reduced the ECAR and increased the OCR. We further determined how reduced ECAR conditions affect proteins that associate with energy sensing and energy response pathways. ERK phosphorylation, SIRT1, and HIF1a decreased while AKT, p38, and AMPK phosphorylation increased. These data document a novel intracellular glycolysis-respiration effect in which restricting glycolysis flux increases mitochondrial respiration. Since this effect can be used to manipulate cell bioenergetic infrastructures, this particular glycolysis-respiration effect can practically inform the development of new mitochondrial medicine approaches. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Methylglyoxal, the dark side of glycolysis

    KAUST Repository

    Allaman, Igor

    2015-02-09

    Glucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity for glycolytic glucose processing in astrocytes compared to neurons. Methylglyoxal, a highly reactive dicarbonyl compound, is inevitably formed as a by-product of glycolysis. Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs), which are associated with several pathologies including diabetes, aging and neurodegenerative diseases. In normal situations, cells are protected against methylglyoxal toxicity by different mechanisms and in particular the glyoxalase system, which represents the most important pathway for the detoxification of methylglyoxal. While the neurotoxic effects of methylglyoxal and AGEs are well characterized, our understanding the glyoxalase system in the brain is more scattered. Considering the high energy requirements (i.e., glucose) of the brain, one should expect that the cerebral glyoxalase system is adequately fitted to handle methylglyoxal toxicity. This review focuses on our actual knowledge on the cellular aspects of the glyoxalase system in brain cells, in particular with regard to its activity in astrocytes and neurons. A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.

  13. Methylglyoxal, the dark side of glycolysis

    Directory of Open Access Journals (Sweden)

    Igor eAllaman

    2015-02-01

    Full Text Available Glucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity for glycolytic glucose processing in astrocytes compared to neurons. Methylglyoxal, a highly reactive dicarbonyl compound, is inevitably formed as a by-product of glycolysis. Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs, which are associated with several pathologies including diabetes, aging and neurodegenerative diseases. The glyoxalase system is the most important pathway for the detoxification of methylglyoxal, and although the neurotoxic effects of methylglyoxal and AGEs are well characterized, less is known about the glyoxalase system in the brain. Considering the high energy requirements (i.e. glucose of the brain, one should expect that the cerebral glyoxalase system is adequately fitted to handle methylglyoxal toxicity. This review focuses on our actual knowledge on the cellular aspects of the glyoxalase system in brain cells, in particular with regards to its activity in astrocytes and neurons. A main emerging concept is that a neuroenergetic specialization is taking place between these two cell types which may serve as a protective mechanism against methylglyoxal-induced toxicity.

  14. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Feasibility study of FDG PET/CT-derived primary tumour glycolysis as a prognostic indicator of survival in patients with non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Mehta, G.; Chander, A.; Huang, C.; Kelly, M.; Fielding, P.

    2014-01-01

    Aim: To assess the feasibility and prognostic value of measuring total lesion glycolysis of the primary tumour (TLG primary ) using combined 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in patients with proven or suspected non-small-cell lung cancer (NSCLC) in the routine diagnostic setting. Materials and methods: At the All wales Research and Diagnostic Positron Emission Tomography Centre in Cardiff (PETIC), in the calendar year 2011, 288 consecutive patients were identified with a single pulmonary mass in whom NSCLC was confirmed or clinically diagnosed following multidisciplinary team review. In a retrospective analysis, for each patient the PET-derived volume of the primary tumour and SUV MEAN was calculated using adaptive thresholds of 40% and 50% of the SUV MAX of the primary tumour. The TLG primary (calculated by volume x SUV MEAN ) was calculated at these two thresholds and was used to predict survival in a multivariate analysis with TNM (tumour, node, metastasis) stage, age, sex, and SUV MAX . The primary endpoint was overall survival over a minimum follow-up of at least 7 months. Results: In virtually every case, the primary tumour could be measured using the automated software with minimal use of manual adjustments. In multivariate analysis, TNM clinical stage, log(TLG primary ) and sex were independent predictors of overall survival. Conclusion: Measurements of primary tumour total lesion glycolysis are simple to perform and provide additional prognostic information over and above that provided by TNM staging

  16. Reducing the genetic complexity of glycolysis in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Solis Escalante, D.

    2015-01-01

    Glycolysis, a biochemical pathway that oxidizes glucose to pyruvate, is at the core of sugar metabolism in Saccharomyces cerevisiae (bakers’ yeast). Glycolysis is not only a catabolic route involved in energy conservation, but also provides building blocks for anabolism. From an applied perspective,

  17. Lysine Deacetylases and Regulated Glycolysis in Macrophages.

    Science.gov (United States)

    Shakespear, Melanie R; Iyer, Abishek; Cheng, Catherine Youting; Das Gupta, Kaustav; Singhal, Amit; Fairlie, David P; Sweet, Matthew J

    2018-06-01

    Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis

    NARCIS (Netherlands)

    Slavov, Nikolai; Budnik, Bogdan A; Schwab, David; Airoldi, Edoardo M; van Oudenaarden, Alexander

    2014-01-01

    Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such

  19. Increased epicardial fat volume quantified by 64-multidetector computed tomography is associated with coronary atherosclerosis and totally occlusive lesions

    International Nuclear Information System (INIS)

    Ueno, Koji; Anzai, Toshihisa; Jinzaki, Masahiro

    2009-01-01

    The relationship between the epicardial fat volume measured by 64-slice multidetector computed tomography (MDCT) and the extension and severity of coronary atherosclerosis was investigated. Both MDCT and conventional coronary angiography (CAG) were performed in 71 consecutive patients who presented with effort angina. The volume of epicardial adipose tissue (EAT) was measured by MDCT. The severity of coronary atherosclerosis was assessed by evaluating the extension of coronary plaques in 790 segments using MDCT data, and the percentage diameter stenosis in 995 segments using CAG data. The estimated volume of EAT indexed by body surface area was defined as VEAT. Increased VEAT was associated with advanced age, male sex, degree of metabolic alterations, a history of acute coronary syndrome (ACS) and the presence of total occlusions, and showed positive correlation with the stenosis score r=0.28, P=0.02) and the atheromatosis score (r=0.67, P 3 /m 2 ) to be the strongest independent determinant of the presence of total occlusions odds ratio 4.64. P=0.02). VEAT correlates with the degree of metabolic alterations and coronary atheromatosis. Excessive accumulation of EAT might contribute to the development of ACS and coronary total occlusions. (author)

  20. Restricting glycolysis impairs brown adipocyte glucose and oxygen consumption

    DEFF Research Database (Denmark)

    Winther, Sally; Isidor, Marie Sophie; Basse, Astrid Linde

    2018-01-01

    During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated kn......During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using si...... of glycolysis, i.e., hexokinase 2 (HK2) and pyruvate kinase M (PKM), respectively, decreased glucose uptake and ISO-stimulated oxygen consumption. HK2 knockdown had a more severe effect, which, in contrast to PKM knockdown, could not be rescued by supplementation with pyruvate. Hence, brown adipocytes rely...... on glucose consumption and glycolytic flux to achieve maximum thermogenic output, with glycolysis likely supporting thermogenesis not only by pyruvate formation but also by supplying intermediates for efferent metabolic pathways....

  1. Impact of lesion morphology on angiographic and clinical outcomes in patients with chronic total occlusion after recanalization with drug-eluting stents: a multislice computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tsuyoshi [Toyohashi Heart Center, Toyohashi (Japan); Nagoya City University Graduate School of Medical Sciences, Department of Cardio-Renal Medicine and Hypertension, Nagoya (Japan); Tsuchikane, Etsuo; Nasu, Kenya; Kimura, Masashi; Terashima, Mitsuyasu; Kinoshita, Yoshihisa; Habara, Maoto; Suzuki, Takahiko [Toyohashi Heart Center, Toyohashi (Japan); Suzuki, Yoriyasu; Ehara, Mariko [Nagoya Heart Center, Nagoya (Japan); Ohte, Nobuyuki [Nagoya City University Graduate School of Medical Sciences, Department of Cardio-Renal Medicine and Hypertension, Nagoya (Japan)

    2015-10-15

    The aim of this study was to investigate the multislice computed tomography (MSCT) parameters associated with adverse outcomes after chronic total occlusion percutaneous coronary intervention (CTO-PCI) with drug-eluting stents. A total of 285 patients who underwent MSCT before CTO-PCI were analyzed. Lesion morphology was assessed with MSCT. Angiographic restenosis, reocclusion, and MACE (a composite of cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization) were analyzed. MACE was observed in 36 patients (13.6 %). Occlusion length was greater (39.5 ± 19.9 mm vs. 22.3 ± 13.7 mm, p < 0.01), minimal vessel area smaller (11.2 ± 5.7 mm{sup 2} vs. 14.5 ± 5.6 mm{sup 2}, p < 0.01), and severe calcification more common (36 % vs. 12 %, p < 0.01) in the MACE group compared to the non-MACE group. We defined occluded length >25.4 mm, minimal vessel area <11.9 mm{sup 2}, which were identified by receiver operating characteristic analysis, and severe calcification as CT-derived risk factors. Angiographic restenosis (60 % vs. 12 % vs. 7 %, p < 0.01), reocclusion (29 % vs. 2 % vs. 2 %, p < 0.01), and MACE (43 % vs. 6 % vs. 3 %, p < 0.01) were more common in patients with 2 or more risk factors than in those with 1 or 0. MSCT characteristics associated with adverse outcomes after CTO-PCI were occlusion length, minimal vessel area, and severe calcification. (orig.)

  2. Glycolysis of poly(3-hydroxybutyrate) via enzyme catalysis

    International Nuclear Information System (INIS)

    Paula, Everton Luiz de; Campos, Tiago Ferreira; Mano, Valdir

    2014-01-01

    Poly(3-hydroxybutyrate), PHB, is a polymer with broad potential applications because of its biodegradability and biocompatibility. However, its high crystallinity is a limiting factor for many applications. To overcome this drawback, one strategy currently employed involves the reduction of the molecular weight of PHB with the concomitant formation of end-functionalized chains, such as those obtained via glycolysis. The glycolysis of PHB can be catalyzed by acid, base, or organometallic compounds. However, to our knowledge, there are no reports regarding PHB glycolysis catalyzed enzymatically. Among the major types of enzymes used in biocatalysis, the lipases stand out because they have the ability to catalyze reactions in both aqueous and organic media. Thus, in this study, we performed the enzymatic glycolysis of PHB using the lipase Amano PS (Pseudomonas cepacia) with ethane-1,2-diol (ethylene glycol) as the functionalizing agent. The results indicated that the glycolysis was successful and afforded hydroxyl-terminated oligomeric PHB polyols. Nuclear magnetic resonance spectra of the products showed characteristic signals for the terminal hydroxyl groups of the polyols, while thermogravimetric and differential scanning calorimetry analyses confirmed an increase in the thermal stability and a decrease in the crystallinity of the polyols compared with the starting PHB polymer, which were both attributed to the reduction in the molecular weight due to glycolysis. (author)

  3. Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat.

    Science.gov (United States)

    Park, Thomas J; Reznick, Jane; Peterson, Bethany L; Blass, Gregory; Omerbašić, Damir; Bennett, Nigel C; Kuich, P Henning J L; Zasada, Christin; Browe, Brigitte M; Hamann, Wiebke; Applegate, Daniel T; Radke, Michael H; Kosten, Tetiana; Lutermann, Heike; Gavaghan, Victoria; Eigenbrod, Ole; Bégay, Valérie; Amoroso, Vince G; Govind, Vidya; Minshall, Richard D; Smith, Ewan St J; Larson, John; Gotthardt, Michael; Kempa, Stefan; Lewin, Gary R

    2017-04-21

    The African naked mole-rat's ( Heterocephalus glaber ) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease. Copyright © 2017, American Association for the Advancement of Science.

  4. [Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

    Science.gov (United States)

    Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

    To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

  5. Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jian-Li Gao

    2015-01-01

    Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

  6. Inhibition of glycolysis by misonidazole in hypoxic cells

    International Nuclear Information System (INIS)

    Ling, L.; Sutherland, R.

    1984-01-01

    Inhibition of glycolysis has been postulated to be a mechanism of misonidazole (MISO) toxicity in hypoxic cells. To investigate the effect of MISO on glycolysis, glucose transport and its consumption and lactate formation were measured. Exponential EMT6 cells (10/sup 6/ cells/ml) were made hypoxix by continuous gassing in 3% CO/sub 2/ in N/sub 2/. They were then treated with 5mM MISO for various times, then washed and analysed for their rates of anaerobic glycolysis. Glucose and lactate content were determined enzymatically. The rates of both glucose consumption and lactate formation decreased after 30 min hypoxic incubation with MISO. After 90 min, the rates were not measurable even though the cells still excluded Trypan Blue. There was, however, a parallel decrease in plating efficiency. These data suggest that the inhibition of glycolysis is an important mechanism of hypoxic toxicity of MISO. To locate the site of inhibition, studies were initiated to look at glucose transport by following the uptake of /sup 14/-C-3-0-methyl-glucose, a nonmetabolised glucose analog. Results obtained so far indicate that up to 90 min of hypoxic incubation with MISO, there was no change in the kinetics of the uptake of his analog. Therefore, the results showed that in hypoxic cells treated with MISO, the glucose transport system was unaffected. However, there was a rapid decrease in anaerobic glycolysis

  7. Glycolysis of poly (3-hydroxybutyrate) catalyzed by an enzyme system

    International Nuclear Information System (INIS)

    Campos, T.F.; Mano, V.

    2010-01-01

    In this work we report the studies of PHB glycolysis catalyzed by lipase Amano PS (Pseudomonas cepacia) in the presence of 1,2-ethanediol (ethylene glycol). The reactions were performed in toluene:dichloroethane 3:1 (v/v) at 60 deg C, varying reaction time and concentration of ethylene glycol. PHB and the products of glycolysis (polyols) were characterized by FTIR, 1 H-NMR, and TG. The FTIR spectra of polyols showed no significant change compared to the spectrum of PHB. The 1 H-NMR spectra of the products of glycolysis showed signs of interest between 3 and 4.7 ppm, related to the ethylene glycol protons inserted in the polymer chain. By analyzing the thermograms we observed that the polyols are more thermally stable than PHB. (author)

  8. Understanding start-up problems in yeast glycolysis.

    Science.gov (United States)

    Overal, Gosse B; Teusink, Bas; Bruggeman, Frank J; Hulshof, Josephus; Planqué, Robert

    2018-05-01

    Yeast glycolysis has been the focus of research for decades, yet a number of dynamical aspects of yeast glycolysis remain poorly understood at present. If nutrients are scarce, yeast will provide its catabolic and energetic needs with other pathways, but the enzymes catalysing upper glycolytic fluxes are still expressed. We conjecture that this overexpression facilitates the rapid transition to glycolysis in case of a sudden increase in nutrient concentration. However, if starved yeast is presented with abundant glucose, it can enter into an imbalanced state where glycolytic intermediates keep accumulating, leading to arrested growth and cell death. The bistability between regularly functioning and imbalanced phenotypes has been shown to depend on redox balance. We shed new light on these phenomena with a mathematical analysis of an ordinary differential equation model, including NADH to account for the redox balance. In order to gain qualitative insight, most of the analysis is parameter-free, i.e., without assigning a numerical value to any of the parameters. The model has a subtle bifurcation at the switch between an inviable equilibrium state and stable flux through glycolysis. This switch occurs if the ratio between the flux through upper glycolysis and ATP consumption rate of the cell exceeds a fixed threshold. If the enzymes of upper glycolysis would be barely expressed, our model predicts that there will be no glycolytic flux, even if external glucose would be at growth-permissable levels. The existence of the imbalanced state can be found for certain parameter conditions independent of the mentioned bifurcation. The parameter-free analysis proved too complex to directly gain insight into the imbalanced states, but the starting point of a branch of imbalanced states can be shown to exist in detail. Moreover, the analysis offers the key ingredients necessary for successful numerical continuation, which highlight the existence of this bistability and the

  9. Experimental determination of control of glycolysis in Lactococcus lactis

    DEFF Research Database (Denmark)

    Købmann, Brian Jensen; Andersen, Heidi Winterberg; Solem, Christian

    2002-01-01

    ), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK) and lactate dehydrogenase (LDH) are shown to have no significant control on the glycolytic flux in exponentially growing cells of L. lactis MG1363. Introduction of an uncoupled ATPase activity results in uncoupling of glycolysis from biomass...... production. With MG1363 growing in defined medium supplemented with glucose, the ATP demanding processes do not have a significant control on the glycolytic flux; it appears that glycolysis is running at maximal rate. It is likely that the flux control is distributed over many enzymes in L. lactis...

  10. Trehalose-6-phosphate synthase and stabilization of yeast glycolysis

    DEFF Research Database (Denmark)

    Fraenkel, Dan; Nielsen, Jens

    2016-01-01

    ‘Lost in transition: Startup of glycolysis yields subpopulations of nongrowing cells…’ (‘LIT’, van Heerden et al. 2014) is a massive paper from groups in Amsterdam and Delft, which deals with broad issues in metabolism and cell heterogeneity, as addressed for the predominant metabolic pathway......, glycolysis, in the context of a long studied but incompletely understood yeast mutant which is impaired in use of glucose without evident direct defects in the pathway. The primary approach is the quite original one of predicting, for the mutant, the dynamics of metabolism upon glucose addition, based...

  11. Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

    NARCIS (Netherlands)

    Chang, Chih-Hao; Curtis, Jonathan D.; Maggi, Leonard B.; Faubert, Brandon; Villarino, Alejandro V.; O'Sullivan, David; Huang, Stanley Ching-Cheng; van der Windt, Gerritje J. W.; Blagih, Julianna; Qiu, Jing; Weber, Jason D.; Pearce, Edward J.; Jones, Russell G.; Pearce, Erika L.

    2013-01-01

    A "switch'' from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete

  12. Discrete event simulations for glycolysis pathway and energy balance

    NARCIS (Netherlands)

    Zwieten, van D.A.J.; Rooda, J.E.; Armbruster, H.D.; Nagy, J.D.

    2010-01-01

    In this report, the biological network of the glycolysis pathway has been modeled using discrete event models (DEMs). The most important feature of this pathway is that energy is released. To create a stable steady-state system an energy molecule equilibrating enzyme and metabolic reactions have

  13. Regulation of glycolysis and level of the Crassulacean acid metabolism.

    Science.gov (United States)

    Pierre, J N; Queiroz, O

    1979-01-01

    Glycolysis shows different patterns of operation and different control steps, depending on whether the level of Crassulacean acid metabolism (CAM) is low or high in the leaves of Kalanchoe blossfeldiana v.Poelln., when subjected to appropriate photoperiodic treatments: at a low level of CAM operation all the enzymes of glycolysis and phosphoenol pyruvate (PEP) carboxylase present a 12 h rhythm of capacity, resulting from the superposition of two 24h rhythms out of phase; phosphofructokinase appears to be the main regulation step; attainment of high CAM level involves (1) an increase in the peak of capacity occurring during the night of all the glycolytic enzymes, thus achieving an over-all 24h rhythm, in strict allometric coherence with the increase in PEP carboxylase capacity, (2) the establishment of different phase relationships between the rhythms of enzyme capacity, and (3) the control of three enzymic steps (phosphofructokinase, the group 3-P-glyceraldehyde dehydrogenase - 3-P-glycerate kinase, and PEP carboxylase). Results show that the hypothesis of allosteric regulation of phosphofructokinase (by PEP) and PEP carboxylase (by malate and glucose-6-P) cannot provide a complete explanation for the temporal organization of glycolysis and that changes in the phase relationships between the rhythms of enzyme capacity along the pathway and a strict correlation between the level of PEP carboxylase capacity and the levels of capacity of the glycolytic enzymes are important components of the regulation of glycolysis in relation to CAM.

  14. Tumor cells and memory T cells converge at glycolysis

    Science.gov (United States)

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-01-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8+ memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate that glycolytic inhibition during the ex vivo clonal expansion of tumor-specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy. PMID:24556820

  15. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Meliana Riwanto

    Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

  16. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    Science.gov (United States)

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

  17. Regulation of glycolysis in brown adipocytes by HIF-1α

    DEFF Research Database (Denmark)

    Basse, Astrid L; Isidor, Marie S; Winther, Sally

    2017-01-01

    Brown adipose tissue takes up large amounts of glucose during cold exposure in mice and humans. Here we report an induction of glucose transporter 1 expression and increased expression of several glycolytic enzymes in brown adipose tissue from cold-exposed mice. Accordingly, these genes were also...... with glucose as the only exogenously added fuel. These data suggest that HIF-1α-dependent regulation of glycolysis is necessary for maximum glucose metabolism in brown adipocytes....

  18. Radiation induces aerobic glycolysis through reactive oxygen species

    International Nuclear Information System (INIS)

    Zhong, Jim; Rajaram, Narasimhan; Brizel, David M.; Frees, Amy E.; Ramanujam, Nirmala; Batinic-Haberle, Ines; Dewhirst, Mark W.

    2013-01-01

    Background and purpose: Although radiation induced reoxygenation has been thought to increase radiosensitivity, we have shown that its associated oxidative stress can have radioprotective effects, including stabilization of the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to promote treatment resistance. Thus, we hypothesized that reoxygenation after radiation would increase glycolysis. We previously showed that blockade of oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation can downregulate HIF-1 activity. Here we tested whether concurrent use of this drug with radiotherapy would reduce the switch to a glycolytic phenotype. Materials and methods: 40 mice with skin fold window chambers implanted with 4T1 mammary carcinomas were randomized into (1) no treatment, (2) radiation alone, (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were imaged on the ninth day following tumor implantation (30 h following radiation treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was measured by using hyperspectral imaging to quantify oxygenation state. Results: Mice treated with radiation showed significantly higher 2-NBDG fluorescence compared to controls (p = 0.007). Hemoglobin saturation analysis demonstrated reoxygenation following radiation, coinciding with the observed increase in glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a significant reduction in 2-NBDG fluorescence compared to effects seen after radiation alone, while having no effect on reoxygenation. Conclusions: Radiation induces an increase in tumor glucose demand approximately 30 h following therapy during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic glycolysis when used

  19. Mushroom body glycolysis is required for olfactory memory in Drosophila.

    Science.gov (United States)

    Wu, Chia-Lin; Chang, Ching-Ching; Wu, Jie-Kai; Chiang, Meng-Hsuan; Yang, Chu-Huai; Chiang, Hsueh-Cheng

    2018-04-01

    Glucose catabolism, also known as glycolysis, is important for energy generation and involves a sequence of enzymatic reactions that convert a glucose molecule into two pyruvate molecules. The glycolysis process generates adenosine triphosphate as a byproduct. In this study, we investigated whether glycolysis plays a role in maintaining neuronal functions in the Drosophila mushroom bodies (MBs), which are generally accepted to be an olfactory learning and memory center. Our data showed that individual knockdown of glycolytic enzymes in the MBs, including hexokinase (HexA), phosphofructokinase (Pfk), or pyruvate kinase (PyK), disrupts olfactory memory. Whole-mount brain immunostaining indicated that pyruvate kinase is strongly expressed in the MB αβ, α'β', and γ neuron subsets. We conclude that HexA, Pfk, and PyK are required in each MB neuron subset for olfactory memory formation. Our data therefore indicates that glucose catabolism in the MBs is important for olfactory memory formation in Drosophila. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. [Mechanism of changes in the rate of glycolysis and levels of ATP and 2,3-diphosphoglycerate in human erythrocytes during aging].

    Science.gov (United States)

    Bogatskaia, L N; Pisaruk, A V

    1987-01-01

    Reasons which have induced changes in the glycolysis rate, ATP and 2,3-diphosphoglycerate content in human erythrocytes with ageing are studied. A fall of the hexokinase activity is shown to be one of the reasons of a significant decrease in the glycolysis rate. The total ATPase activity in erythrocytes does not change with the age. At the same time the decay rate of 2,3-diphosphoglycerate increases, that, evidently, is one of the reasons of the 2,3-diphosphoglycerate content decrease in erythrocytes with ageing.

  1. Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

    Science.gov (United States)

    Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

    2017-09-01

    Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

  2. 24-h organization of glycolysis and control by photoperiodism.

    Science.gov (United States)

    Pierre, J N; Celati, C; Queiroz, O

    1985-01-01

    A study of the temporal organization of glycolysis at diverse levels of activity of the pathway showed that consideration of the phases of the 24h oscillations in glycolytic pools affords a means of detecting modifications in regulatory mechanisms according to the level of carbon flow along the pathway. The work utilized Kalanchoe blossfeldiana, a plant with crassulacean acid metabolism (CAM) in which glycolytic activity is under the control of photoperiodism: after transfer from long days to short days carbon flow through the pathway increases drastically. Analysis of the glycolytic pools performed during the day/night cycle showed that: a. 24 h-period variations exist in the content of the glycolytic intermediates; b. time of the acrophase of these rhythms changes as a function of the photoperiodic treatment: in long days the pools of the intermediates preceding the phosphofructokinase (PFK) step oscillate in phase and the same holds for the intermediates after the PFK step but these two sequences of the pathway oscillate out of phase (phase-jump of about 10h); transfer to short days besides producing (after a lag) changes in the mean level and amplitude of the oscillations, modifies their phase: this temporal reorganization of glycolysis results in splitting the pathway into 3 sequences of synchronously-oscillating pools, phase-jumps between successive sequences occurring at the PFK (4h) and at the 3-phosphoglyceraldehyde dehydrogenase (12h) steps.

  3. Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Holcombe, Andrea; Ammann, Eric; Espeland, Mark A; Kelley, Brendan J; Manson, JoAnn E; Wallace, Robert; Robinson, Jennifer

    2017-10-01

    To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women. Published by Elsevier Inc.

  4. Implications of the simultaneous occurrence of glycolysis and gluconeogenesis in hepatocytes from normal and hyperthyroid rats

    International Nuclear Information System (INIS)

    Phillips, J.W.; Berry, M.N.

    2001-01-01

    The mammalian liver has the capability for both glycolysis and gluconeogenesis. In the fasting state, metabolites such as lactate and glycerol, generated in the peripheral tissues, are taken up by the liver and converted to glucose. However, hepatocytes from fasted animals are also capable of substantial rates of glycolysis. It is generally assumed that glycolysis and gluconeogenesis do not occur simultaneously in the same cell, but rather the metabolic conditions that facilitate flux through one pathway impair flow in the opposite direction. The actual direction of flow at any given moment is thought to be determined by regulatory mechanisms that control flux through the enzymatic steps specific to glycolysis and gluconeogenesis. The rates of glycolysis from [6- 3 H]glucose and gluconeogenesis from [U- 14 C]glycerol were determined in isolated hepatocytes from fasted normal and hyperthyroid rats. We observed that glycolysis from glucose and glucose synthesis from glycerol occurred simultaneously at substantial rates in hepatocytes from normal rats and that gluconeogenesis, but not glycolysis, was increased twofold in hepatocytes from thyroid treated rats. In the hyperthyroid state, the rate of glycolysis from glucose was approximately equal to the rate of glucose formation from glycerol. Hence, metabolism and ATP turnover were stimulated without substantially altering steady-state concentrations of glucose. The concomitant operation of hepatic glycolysis and gluconeogenesis may be a mechanism that accounts in part for the calorigenic effect of thyroid hormone. Since hepatocyles are generally impermeable to phosphorylated metabolites, our observations suggest that glycolysis, and phosphorylation of glycerol take place in the same cells, and that the occurrence of simultaneous glycolysis and gluconeogenesis is an indication of channelling within the hepatocyte cytoplasm of individual hepatocytes

  5. Modelling response of glycolysis in S. cerevisiae cells harvested at diauxic shift.

    NARCIS (Netherlands)

    Albers, E.; Bakker, B.M.; Gustafsson, L.

    2002-01-01

    The response of glycolysis to exposure of glucose in non-growing S. cerevisiae cells from diauxic shift was monitored. The result was compared to a kinetic model of glycolysis with branches to glycogen, trehalose, glycerol, and succinate. Experimental data at steady-state concentrations of

  6. Glycolysis and the significance of lactate in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Keri Linda Carpenter

    2015-04-01

    Full Text Available In traumatic brain injury (TBI patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well recognised, and are associated statistically with unfavourable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolised via glycolysis (Embden-Meyerhof-Parnas pathway to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate’s association with unfavourable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilise lactate by feeding into the tricarboxylic acid (TCA cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilisation of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of 13C-labelled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with 13C NMR analysis, revealed 13C labelling in glutamine consistent with lactate utilisation via the TCA cycle. This suggests that where neurons are too damaged to utilise the lactate produced from glucose by astrocytes, i.e. uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining association between high lactate and poor outcome. An intravenous exogenous lactate supplementation study in TBI patients showed evidence for a beneficial effect judged by surrogate endpoints. Here we review current knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better

  7. Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells

    International Nuclear Information System (INIS)

    Bhatt, Anant Narayan; Chauhan, Ankit; Khanna, Suchit; Rai, Yogesh; Singh, Saurabh; Soni, Ravi; Kalra, Namita; Dwarakanath, Bilikere S

    2015-01-01

    Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage

  8. The success of opening single chronic total occlusion lesions to improve myocardialviabilitytrial (SOS-COMEDY): Study protocol of a prospective multicenter study.

    Science.gov (United States)

    Huang, Rongchong; Song, Xiantao; Zhang, Haishan; Tian, Wen; Huang, Zheng; Zhang, Xingwei; Yang, Junqing; Zhang, Dongfeng; Wu, Jian; Zhong, Lei; Ting, Henry H

    2018-04-01

    Success of opening single (SOS)-comedy is a prospective multicenter study to compare the improvement in the decrease of myocardial viability by percutaneous coronary intervention (PCI) with that by optimal medical therapy (OMT) alone in patients with chronic total occlusion (CTO) of a single coronary artery. The risks and the benefits of both options (PCI and OMT) were listed in a CTO decision aid (DA). Eligible participants detected by invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) were divided into PCI or OMT groups according to patients' choice after shared-decision making process with DA. Participants will undergo positron emission tomography/computed tomography (PET/CT), cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE), and proceed to ICA and revascularization if possible. Blinded core laboratory interpretation will be performed for ICA, CCTA, PET/CT, CMR, and TTE. All participants will be followed up for 12 months. The primary endpoint is the improvement to the decrease of myocardial viability from baseline assessed with the use of PET/CT after 12-month follow-up. All of the patients are appropriately consented before enrolling in this study, which has been approved by the Ethics Committee. Results of SOS-COMEDY will be helpful to develop a strategy for single CTO patients.

  9. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    Directory of Open Access Journals (Sweden)

    Johann eSteiner

    2014-11-01

    Full Text Available Clozapine has stronger systemic metabolic side effects than haloperidol and it was hypothesized that therapeutic antipsychotic and adverse metabolic effects might be related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production.Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT and monocarboxylate (MCT transporters was determined after 6h and 24h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed.Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside.Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  10. Linking tumor glycolysis and immune evasion in cancer: Emerging concepts and therapeutic opportunities.

    Science.gov (United States)

    Ganapathy-Kanniappan, Shanmugasundaram

    2017-08-01

    Metabolic reprogramming and immune evasion are two hallmarks of cancer. Metabolic reprogramming is exemplified by cancer's propensity to utilize glucose at an exponential rate which in turn is linked with "aerobic glycolysis", popularly known as the "Warburg effect". Tumor glycolysis is pivotal for the efficient management of cellular bioenergetics and uninterrupted cancer growth. Mounting evidence suggests that tumor glycolysis also plays a key role in instigating immunosuppressive networks that are critical for cancer cells to escape immune surveillance ("immune evasion"). Recent data show that induction of cellular stress or metabolic dysregulation sensitize cancer cells to antitumor immune cells implying that metabolic reprogramming and immune evasion harmonize during cancer progression. However, the molecular link between these two hallmarks of cancer remains obscure. In this review the molecular intricacies of tumor glycolysis that facilitate immune evasion has been discussed in the light of recent research to explore immunotherapeutic potential of targeting cancer metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Glycolysis in contracting rat skeletal muscle is controlled by factors related to energy state

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Macdonald, Will A; Sahlin, Kent

    2009-01-01

    The control of glycolysis in contracting muscle is not fully understood. The aim of the present study was to examine whether activation of glycolysis is mediated by factors related to the energy state or by a direct effect of Ca2+ on the regulating enzymes. Extensor digitorum longus muscles from...... and 58% of those in Con respectively. Glycolytic rate in BTS was only 51% of that in Con but the relative contribution of ATP derived from PCr (phosphocreatine) and glycolysis and the relation between muscle contents of PCr and Lac (lactate) were not different. Prolonged cyanide incubation of quiescent...... contribution of energy delivered from PCr and glycolysis during both conditions suggests that the glycolytic rate is controlled by factors related to energy state....

  12. Tissue Respiration and Glycolysis in the Development of Acute Radiation Sickness

    National Research Council Canada - National Science Library

    Golubentsev, D

    1960-01-01

    The condition of tissue respiration and glycolysis in the development of acute radiation sickness has been insufficiently studied, and the factual data and opinions of various investigators are frequently contradictory...

  13. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells

    NARCIS (Netherlands)

    Everts, Bart; Amiel, Eyal; van der Windt, Gerritje J. W.; Freitas, Tori C.; Chott, Robert; Yarasheski, Kevin E.; Pearce, Erika L.; Pearce, Edward J.

    2012-01-01

    TLR agonists initiate a rapid activation program in dendritic cells (DCs) that requires support from metabolic and bioenergetic resources. We found previously that TLR signaling promotes aerobic glycolysis and a decline in oxidative phosphorylation (OXHPOS) and that glucose restriction prevents

  14. Inhaled Beta2-agonist increases power output and glycolysis during sprinting in men

    DEFF Research Database (Denmark)

    Kalsen, Anders; Hostrup, Morten; Söderlund, Karin

    2016-01-01

    . Moreover, net rate of glycogenolysis (6.5±0.8 vs. 3.1±0.7 mmol glucosyl units kg dw s) and glycolysis (2.4±0.2 vs. 1.6±0.2 mmol glucosyl units kg dw s) were higher (P... and glycolysis in skeletal muscles. Furthermore, as terbutaline counteracted a reduction in ATP in type II fibers, terbutaline may postpone fatigue development in these fibers....

  15. Tumor cells and memory T cells converge at glycolysis: Therapeutic implications

    OpenAIRE

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-01-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8+ memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. ...

  16. Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells.

    Directory of Open Access Journals (Sweden)

    Ayako Nakano

    Full Text Available Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2, KG-1 (ABCB1 and HepG2 cells (ABCB1 and ABCG2. Interestingly, although side population (SP cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells.

  17. Glycolysis of poly(3-hydroxybutyrate) via enzyme catalysis; Glicolise do poli(3-hidroxibutirato) por via enzimatica

    Energy Technology Data Exchange (ETDEWEB)

    Paula, Everton Luiz de, E-mail: everton2804@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Quimica; Campos, Tiago Ferreira; Mano, Valdir [Universidade Federal de Sao Joao del-Rei (UFSJ), MG (Brazil). Departamento de Ciencias Naturais

    2014-05-15

    Poly(3-hydroxybutyrate), PHB, is a polymer with broad potential applications because of its biodegradability and biocompatibility. However, its high crystallinity is a limiting factor for many applications. To overcome this drawback, one strategy currently employed involves the reduction of the molecular weight of PHB with the concomitant formation of end-functionalized chains, such as those obtained via glycolysis. The glycolysis of PHB can be catalyzed by acid, base, or organometallic compounds. However, to our knowledge, there are no reports regarding PHB glycolysis catalyzed enzymatically. Among the major types of enzymes used in biocatalysis, the lipases stand out because they have the ability to catalyze reactions in both aqueous and organic media. Thus, in this study, we performed the enzymatic glycolysis of PHB using the lipase Amano PS (Pseudomonas cepacia) with ethane-1,2-diol (ethylene glycol) as the functionalizing agent. The results indicated that the glycolysis was successful and afforded hydroxyl-terminated oligomeric PHB polyols. Nuclear magnetic resonance spectra of the products showed characteristic signals for the terminal hydroxyl groups of the polyols, while thermogravimetric and differential scanning calorimetry analyses confirmed an increase in the thermal stability and a decrease in the crystallinity of the polyols compared with the starting PHB polymer, which were both attributed to the reduction in the molecular weight due to glycolysis. (author)

  18. The selective control of glycolysis, gluconeogenesis and glycogenesis by temporal insulin patterns.

    Science.gov (United States)

    Noguchi, Rei; Kubota, Hiroyuki; Yugi, Katsuyuki; Toyoshima, Yu; Komori, Yasunori; Soga, Tomoyoshi; Kuroda, Shinya

    2013-05-14

    Insulin governs systemic glucose metabolism, including glycolysis, gluconeogenesis and glycogenesis, through temporal change and absolute concentration. However, how insulin-signalling pathway selectively regulates glycolysis, gluconeogenesis and glycogenesis remains to be elucidated. To address this issue, we experimentally measured metabolites in glucose metabolism in response to insulin. Step stimulation of insulin induced transient response of glycolysis and glycogenesis, and sustained response of gluconeogenesis and extracellular glucose concentration (GLC(ex)). Based on the experimental results, we constructed a simple computational model that characterises response of insulin-signalling-dependent glucose metabolism. The model revealed that the network motifs of glycolysis and glycogenesis pathways constitute a feedforward (FF) with substrate depletion and incoherent feedforward loop (iFFL), respectively, enabling glycolysis and glycogenesis responsive to temporal changes of insulin rather than its absolute concentration. In contrast, the network motifs of gluconeogenesis pathway constituted a FF inhibition, enabling gluconeogenesis responsive to absolute concentration of insulin regardless of its temporal patterns. GLC(ex) was regulated by gluconeogenesis and glycolysis. These results demonstrate the selective control mechanism of glucose metabolism by temporal patterns of insulin.

  19. Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa.

    Science.gov (United States)

    Petit, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; Punzo, Claudio

    2018-05-29

    Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Glycolysis and mitochondrial respiration in mouse LDHC-null sperm.

    Science.gov (United States)

    Odet, Fanny; Gabel, Scott; London, Robert E; Goldberg, Erwin; Eddy, Edward M

    2013-04-01

    We demonstrated previously that a knockout (KO) of the lactate dehydrogenase type C (Ldhc) gene disrupted male fertility and caused a considerable reduction in sperm glucose consumption, ATP production, and motility. While that study used mice with a mixed genetic background, the present study used C57BL/6 (B6) and 129S6 (129) Ldhc KO mice. We found that B6 KO males were subfertile and 129 KO males were infertile. Sperm from 129 wild-type (WT) mice have a lower glycolytic rate than sperm from B6 WT mice, resulting in a greater reduction in ATP production in 129 KO sperm than in B6 KO sperm. The lower glycolytic rate in 129 sperm offered a novel opportunity to examine the role of mitochondrial respiration in sperm ATP production and motility. We observed that in media containing a mitochondrial substrate (pyruvate or lactate) as the sole energy source, ATP levels and progressive motility in 129 KO sperm were similar to those in 129 WT sperm. However, when glucose was added, lactate was unable to maintain ATP levels or progressive motility in 129 KO sperm. The rate of respiration (ZO2) was high when 129 KO or WT sperm were incubated with lactate alone, but addition of glucose caused a reduction in ZO2. These results indicate that in the absence of glucose, 129 sperm can produce ATP via oxidative phosphorylation, but in the presence of glucose, oxidative phosphorylation is suppressed and the sperm utilize aerobic glycolysis, a phenomenon known as the Crabtree effect.

  1. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

    International Nuclear Information System (INIS)

    Ackermann, R.F.; Lear, J.L.

    1989-01-01

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [ 18 F]fluorodeoxyglucose (FDG) and [ 14 C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the 14 C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14 C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum

  2. Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling

    Directory of Open Access Journals (Sweden)

    Hong-tao Song

    2014-01-01

    Full Text Available To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells. We observed consistent increasing of glucose consumption and lactate production, typical features of anaerobic glycolysis, suggesting that AEG-1 may promote anaerobic glycolysis. Moreover, we noted that AMPK phosphorylation at Thr172 as well as pPFK2 (Ser466 was increased in NCM460 cells overexpressing AEG-1. Compound C may block AMPK and PFK2 phosphorylation in both control and AEG-1-overexpressed cells and decrease the glucose consumption and lactate production. The present findings indicated that reduced AEG-1 protein levels by RNAi may decrease the glucose consumption and lactate production in HCT116 colorectal carcinoma cells. The present identified AEG-1/AMPK/PFK2 glycolysis cascade may be essential to cell proliferation and tumor growth. The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG-1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.

  3. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

    Energy Technology Data Exchange (ETDEWEB)

    Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Tabibzadeh, Siamak, E-mail: fbs@bioscience.org [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Dept of Oncologic Radiology, University of California, Irvine, CA (United States)

    2014-06-13

    Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

  4. Glycolysis Is Dynamic and Relates Closely to Respiration Rate in Stored Sugarbeet Roots

    Directory of Open Access Journals (Sweden)

    Clarice A. Megguer

    2017-05-01

    Full Text Available Although respiration is the principal cause of the loss of sucrose in postharvest sugarbeet (Beta vulgaris L., the internal mechanisms that control root respiration rate are unknown. Available evidence, however, indicates that respiration rate is likely to be controlled by the availability of respiratory substrates, and glycolysis has a central role in generating these substrates. To determine glycolytic changes that occur in sugarbeet roots after harvest and to elucidate relationships between glycolysis and respiration, sugarbeet roots were stored for up to 60 days, during which activities of glycolytic enzymes and concentrations of glycolytic substrates, intermediates, cofactors, and products were determined. Respiration rate was also determined, and relationships between respiration rate and glycolytic enzymes and metabolites were evaluated. Glycolysis was highly variable during storage, with 10 of 14 glycolytic activities and 14 of 17 glycolytic metabolites significantly altered during storage. Changes in glycolytic enzyme activities and metabolites occurred throughout the 60 day storage period, but were greatest in the first 4 days after harvest. Positive relationships between changes in glycolytic enzyme activities and root respiration rate were abundant, with 10 of 14 enzyme activities elevated when root respiration was elevated and 9 glycolytic activities static during periods of unchanging respiration rate. Major roles for pyruvate kinase and phosphofructokinase in the regulation of postharvest sugarbeet root glycolysis were indicated based on changes in enzymatic activities and concentrations of their substrates and products. Additionally, a strong positive relationship between respiration rate and pyruvate kinase activity was found indicating that downstream TCA cycle enzymes were unlikely to regulate or restrict root respiration in a major way. Overall, these results establish that glycolysis is not static during sugarbeet root

  5. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain

  6. Histological data concerning the pig (sus scrofa) for use in radiobiology. I. Normal histology of certain systems. 2. Injuries caused by total {gamma} irradiation; Donnees histologiques sur le porc (sus scrofa), utilisables en radiobiologie. 1. histologie normale de certains appareils. 2. etude des lesions consecutives a une irradiation {gamma} totale

    Energy Technology Data Exchange (ETDEWEB)

    Guenet, J.L.; Vaiman, M.; Nizza, P. [Commissariat a L' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1966-06-01

    The domestic pig lately become a laboratory whose anatomical and physiological characteristics appear to be appreciated for certain radiological studies. In this report the authors describe research which they have carried out (in particular in the field of histology) on domestic pigs of different species with a view to compiling a record which might be of help to future workers in this field. The second part of their work deals with anatomical and histological injuries caused by total exposure to gamma radiation from cobalt 60 at doses of around 285 rads. (authors) [French] Le porc domestique est devenu depuis peu un animal de laboratoire, dont les caracteristiques anatomiques et physiologiques paraissent fort appreciees pour certaines etudes de radiobiologie. Dans ce rapport les auteurs font part des recherches qu'ils ont effectuees (notamment dans le domaine de l'histologie) sur des porcs domestiques de differentes races, de maniere a constituer un document capable de venir en aide aux utilisateurs eventuels. La deuxieme partie de leur travail traite de lesions anatomiques et histologiques, consecutives a des expositions totales aux rayonnements gamma du cobalt 60 a des doses voisines de 285 rads. (auteurs)

  7. Histological data concerning the pig (sus scrofa) for use in radiobiology. I. Normal histology of certain systems. 2. Injuries caused by total {gamma} irradiation; Donnees histologiques sur le porc (sus scrofa), utilisables en radiobiologie. 1. histologie normale de certains appareils. 2. etude des lesions consecutives a une irradiation {gamma} totale

    Energy Technology Data Exchange (ETDEWEB)

    Guenet, J L; Vaiman, M; Nizza, P [Commissariat a L' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1966-06-01

    The domestic pig lately become a laboratory whose anatomical and physiological characteristics appear to be appreciated for certain radiological studies. In this report the authors describe research which they have carried out (in particular in the field of histology) on domestic pigs of different species with a view to compiling a record which might be of help to future workers in this field. The second part of their work deals with anatomical and histological injuries caused by total exposure to gamma radiation from cobalt 60 at doses of around 285 rads. (authors) [French] Le porc domestique est devenu depuis peu un animal de laboratoire, dont les caracteristiques anatomiques et physiologiques paraissent fort appreciees pour certaines etudes de radiobiologie. Dans ce rapport les auteurs font part des recherches qu'ils ont effectuees (notamment dans le domaine de l'histologie) sur des porcs domestiques de differentes races, de maniere a constituer un document capable de venir en aide aux utilisateurs eventuels. La deuxieme partie de leur travail traite de lesions anatomiques et histologiques, consecutives a des expositions totales aux rayonnements gamma du cobalt 60 a des doses voisines de 285 rads. (auteurs)

  8. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  9. Anaerobic glycolysis as a property of malignant cells and its application aspects

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Korogodin, V.I.

    1996-01-01

    Under hypoxia excess glucose causes fast death of malignant cells without affecting viability of benign tumor and normal tissue cells. Laws and mechanisms of this phenomenon are described. Relationship between glycolysis activation and malignant degeneration of normal cells, application of artificial hyperglycemia to cancer therapy are discussed. 21 refs., 5 figs., 2 tabs

  10. Recycling of PUR scrap from car seats-glycolysis of flexible PUR foam

    Czech Academy of Sciences Publication Activity Database

    Beneš, Hynek; Holler, Petr; Schmidt, Pavel; Horák, Zdeněk; Rösner, J.

    2005-01-01

    Roč. 99, - (2005), s. 29 ISSN 0009-2770. [International Conference on Polymeric Materials in Automotive , Slovak Rubber Conference /17./. 10.5.2005-12.5.2005, Bratislava] Institutional research plan: CEZ:AV0Z40500505 Keywords : chemical recycling * flexible polyurethane foam * glycolysis Subject RIV: CD - Macromolecular Chemistry

  11. Limits to sustainable muscle performance: interaction between glycolysis and oxidative phosphorylation.

    Science.gov (United States)

    Conley, K E; Kemper, W F; Crowther, G J

    2001-09-01

    This paper proposes a mechanism responsible for setting the sustainable level of muscle performance. Our contentions are that the sustainable work rate is determined (i) at the muscle level, (ii) by the ability to maintain ATP supply and (iii) by the products of glycolysis that may inhibit the signal for oxidative phosphorylation. We argue below that no single factor 'limits' sustainable performance, but rather that the flux through and the interaction between glycolysis and oxidative phosphorylation set the level of sustainable ATP supply. This argument is based on magnetic resonance spectroscopy measurements of the sources and sinks for energy in vivo in human muscle and rattlesnake tailshaker muscle during sustained contractions. These measurements show that glycolysis provides between 20% (human muscle) and 40% (tailshaker muscle) of the ATP supply during sustained contractions in these muscles. We cite evidence showing that this high glycolytic flux does not reflect an O(2) limitation or mitochondria operating at their capacity. Instead, this flux reflects a pathway independent of oxidative phosphorylation for ATP supply during aerobic exercise. The consequence of this high glycolytic flux is accumulation of H(+), which we argue inhibits the rise in the signal activating oxidative phosphorylation, thereby restricting oxidative ATP supply to below the oxidative capacity. Thus, both glycolysis and oxidative phosphorylation play important roles in setting the highest steady-state ATP synthesis flux and thereby determine the sustainable level of work by exercising muscle.

  12. Glycolysis and ATP degradation in cod ( Gadus morhua ) at subzero temperatures in relation to thaw rigor

    DEFF Research Database (Denmark)

    Cappeln, Gertrud; Jessen, Flemming

    2001-01-01

    Glycolysis was shown to occur during freezing of cod of decrease in glycogen and an increase in lactate. In addition, the ATP content decreased during freezing. Synthesis of ATP was measured as degradation of glycogen. During storage at -9 and - 12 degreesC it was found that degradation of ATP...

  13. Control of Glycolysis by Glyceraldehyde-3-Phosphate Dehydrogenase in Streptococcus cremoris and Streptococcus lactis

    NARCIS (Netherlands)

    POOLMAN, B; BOSMAN, B; KONINGS, WN

    1987-01-01

    The decreased response of the energy metabolism of lactose-starved Streptococcus cremoris upon readdition of lactose is caused by a decrease of the glycolytic activity. The decrease in glycolysis is accompanied by a decrease in the activities of glyceraldehyde-3-phosphate dehydrogenase and

  14. AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells

    International Nuclear Information System (INIS)

    Shimura, Tsutomu; Noma, Naoto; Sano, Yui; Ochiai, Yasushi; Oikawa, Toshiyuki; Fukumoto, Manabu; Kunugita, Naoki

    2014-01-01

    Background and purpose: Cellular radioresistance is a major impediment to effective radiotherapy. Here, we demonstrated that long-term exposure to fractionated radiation conferred acquired radioresistance to tumor cells due to AKT-mediated enhanced aerobic glycolysis. Material and methods: Two human tumor cell lines with acquired radioresistance were established by long-term exposure to fractionated radiation with 0.5 Gy of X-rays. Glucose uptake was inhibited using 2-deoxy-D-glucose, a non-metabolizable glucose analog. Aerobic glycolysis was assessed by measuring lactate concentrations. Cells were then used for assays of ROS generation, survival, and cell death as assessed by annexin V staining. Results: Enhanced aerobic glycolysis was shown by increased glucose transporter Glut1 expression and a high lactate production rate in acquired radioresistant cells compared with parental cells. Inhibiting the AKT pathway using the AKT inhibitor API-2 abrogated these phenomena. Moreover, we found that inhibiting glycolysis with 2-deoxy-D-glucose suppressed acquired tumor cell radioresistance. Conclusions: Long-term fractionated radiation confers acquired radioresistance to tumor cells by AKT-mediated alterations in their glucose metabolic pathway. Thus, tumor cell metabolic pathway is an attractive target to eliminate radioresistant cells and improve radiotherapy efficacy

  15. Constant Growth Rate Can Be Supported by Decreasing Energy Flux and Increasing Aerobic Glycolysis

    Directory of Open Access Journals (Sweden)

    Nikolai Slavov

    2014-05-01

    Full Text Available Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration and of mitochondrial folate-mediated NADPH production (required for oxidative defense. The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival.

  16. Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose

    Science.gov (United States)

    Heerden, Johan H. v.; Wortel, Meike T.; Bruggeman, Frank J.; Heijnen, Joseph J.; Bollen, Yves J.; Planqué, Robert; Hulshof, Josephus; O’Toole, Tom G.; Wahl, S. A.; Teusink, Bas

    2014-01-01

    In the model eukaryote Saccharomyces cerevisiae, it has long been known that a functional trehalose pathway is indispensable for transitions to high glucose conditions. Upon addition of glucose, cells with a defect in trehalose 6-phosphate synthase (Tps1), the first committed step in the trehalose pathway, display what we have termed an imbalanced glycolytic state; in this state the flux through the upper part of glycolysis outpaces that through the lower part of glycolysis. As a consequence, the intermediate fructose 1,6-bisphosphate (FBP) accumulates at low concentrations of ATP and inorganic phosphate (Pi). Despite significant research efforts, a satisfactory understanding of the regulatory role that trehalose metabolism plays during such transitions has remained infamously unresolved. In a recent study, we demonstrate that the startup of glycolysis exhibits two dynamic fates: a proper, functional, steady state or the imbalanced state described above. Both states are stable, attracting states, and the probability distribution of initial states determines the fate of a yeast cell exposed to glucose. Trehalose metabolism steers the dynamics of glycolysis towards the proper functional state through its ATP hydrolysis activity; a mechanism that ensures that the demand and supply of ATP is balanced with Pi availability under dynamic conditions. [van Heerden et al. Science (2014), DOI: 10.1126/science.1245114.] PMID:28357229

  17. Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose

    Directory of Open Access Journals (Sweden)

    Johan H. van Heerden

    2015-02-01

    Full Text Available In the model eukaryote Saccharomyces cerevisiae, it has long been known that a functional trehalose pathway is indispensable for transitions to high glucose conditions. Upon addition of glucose, cells with a defect in trehalose 6-phosphate synthase (Tps1, the first committed step in the trehalose pathway, display what we have termed an imbalanced glycolytic state; in this state the flux through the upper part of glycolysis outpaces that through the lower part of glycolysis. As a consequence, the intermediate fructose 1,6-bisphosphate (FBP accumulates at low concentrations of ATP and inorganic phosphate (Pi. Despite significant research efforts, a satisfactory understanding of the regulatory role that trehalose metabolism plays during such transitions has remained infamously unresolved. In a recent study, we demonstrate that the startup of glycolysis exhibits two dynamic fates: a proper, functional, steady state or the imbalanced state described above. Both states are stable, attracting states, and the probability distribution of initial states determines the fate of a yeast cell exposed to glucose. Trehalose metabolism steers the dynamics of glycolysis towards the proper functional state through its ATP hydrolysis activity; a mechanism that ensures that the demand and supply of ATP is balanced with Pi availability under dynamic conditions. [van Heerden et al. Science (2014, DOI: 10.1126/science.1245114.

  18. Glycolysis is governed by growth regime and simple enzyme regulation in adherent MDCK cells.

    Science.gov (United States)

    Rehberg, Markus; Ritter, Joachim B; Reichl, Udo

    2014-10-01

    Due to its vital importance in the supply of cellular pathways with energy and precursors, glycolysis has been studied for several decades regarding its capacity and regulation. For a systems-level understanding of the Madin-Darby canine kidney (MDCK) cell metabolism, we couple a segregated cell growth model published earlier with a structured model of glycolysis, which is based on relatively simple kinetics for enzymatic reactions of glycolysis, to explain the pathway dynamics under various cultivation conditions. The structured model takes into account in vitro enzyme activities, and links glycolysis with pentose phosphate pathway and glycogenesis. Using a single parameterization, metabolite pool dynamics during cell cultivation, glucose limitation and glucose pulse experiments can be consistently reproduced by considering the cultivation history of the cells. Growth phase-dependent glucose uptake together with cell-specific volume changes generate high intracellular metabolite pools and flux rates to satisfy the cellular demand during growth. Under glucose limitation, the coordinated control of glycolytic enzymes re-adjusts the glycolytic flux to prevent the depletion of glycolytic intermediates. Finally, the model's predictive power supports the design of more efficient bioprocesses.

  19. Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.

    Science.gov (United States)

    Kanatsu-Shinohara, Mito; Tanaka, Takashi; Ogonuki, Narumi; Ogura, Atsuo; Morimoto, Hiroko; Cheng, Pei Feng; Eisenman, Robert N; Trumpp, Andreas; Shinohara, Takashi

    2016-12-01

    Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division. © 2016 Kanatsu-Shinohara et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Tumor cells and memory T cells converge at glycolysis: therapeutic implications.

    Science.gov (United States)

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-05-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8(+) memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate that glycolytic inhibition during the ex vivo clonal expansion of tumor-specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy.

  1. The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.

    Science.gov (United States)

    Godzik, Katharina; Coleman, Michael P

    2015-04-01

    The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.

  2. Study of genital lesions

    Directory of Open Access Journals (Sweden)

    Anand Kumar B

    2003-03-01

    Full Text Available A total of one hundred patients (75 males and 25 females age ranged from 17-65 years with genital lesions attending the STD clinic of Bowring and LC Hospitals Bangalore constituted the study group. Based on clinical features, the study groups were classified as syphilis (39, chancroid (30, herpes genitolis (13, condylomato lato (9, LGV (7t condylomata acuminata (5, genital scabies (3, granuloma inguinole (2 and genital candidiasis (1. In 68% microbiological findings confirmed the clinical diagnosis. Of the 100 cases 13% and 2% were positive for HIV antibodies and HbsAg respectively.

  3. Post-radiotherapeutic heart lesions

    International Nuclear Information System (INIS)

    Testart, F.M.

    1979-05-01

    Heart structures have traditionally been considered radioresistant. In fact all tissues subjected to radiotherapy can develop lesions. Possible damage includes: - pericardiac fibrosis, the commonest and best individualized, associated with a constriction this leads to a stoppage pattern usually occurring late, around the 18th month. Its frequency depends directly on the total radiation dose; - fibrous myocarditis by direct damage to the heart muscle; - stenosis type lesions of the large coronary trunks; - in exceptional cases lesions of the aorta: hyperplastic degenerescence of the intima and adventitia or of the aortic sigmoid valvules and the mitral valves. Three observations are reported, concerning a coronary, a pericardiac and a coronary, myocardiac and pericardiac lesion. Following this account the irradiation techniques and main experimental data are reviewed and the prophylactic and therapeutic consequences to be derived from our observations and those of the literature are examined [fr

  4. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the (V600E)BRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to (V600E)BRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS......). Notably, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that (V600E)BRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes...

  5. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the V600EBRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS). Notably......, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that V600EBRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes an addiction to V...

  6. Human papillomavirus in oral lesions Virus papiloma humano en lesiones orales

    OpenAIRE

    Joaquín V. Gónzalez; Rafael A. Gutiérrez; Alicia Keszler; Maria Del Carmen Colacino; Lidia V. Alonio; Angélica R. Teyssie; Maria Alejandra Picconi

    2007-01-01

    Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell ...

  7. Impaired mitochondrial Ca2+ homeostasis in respiratory chain-deficient cells but efficient compensation of energetic disadvantage by enhanced anaerobic glycolysis due to low ATP steady state levels

    International Nuclear Information System (INIS)

    Kleist-Retzow, Juergen-Christoph von; Hue-Tran Hornig-Do; Schauen, Matthias; Eckertz, Sabrina; Tuan Anh Duong Dinh; Stassen, Frank; Lottmann, Nadine; Bust, Maria; Galunska, Bistra; Wielckens, Klaus; Hein, Wolfgang; Beuth, Joseph; Braun, Jan-Matthias; Fischer, Juergen H.; Ganitkevich, Vladimir Y.; Maniura-Weber, Katharina; Wiesner, Rudolf J.

    2007-01-01

    Energy-producing pathways, adenine nucleotide levels, oxidative stress response and Ca 2+ homeostasis were investigated in cybrid cells incorporating two pathogenic mitochondrial DNA point mutations, 3243A > G and 3302A > G in tRNA Leu(UUR) , as well as Rho 0 cells and compared to their parental 143B osteosarcoma cell line. All cells suffering from a severe respiratory chain deficiency were able to proliferate as fast as controls. The major defect in oxidative phosphorylation was efficiently compensated by a rise in anaerobic glycolysis, so that the total ATP production rate was preserved. This enhancement of glycolysis was enabled by a considerable decrease of cellular total adenine nucleotide pools and a concomitant shift in the AMP + ADP/ATP ratios, while the energy charge potential was still in the normal range. Further important consequences were an increased production of superoxide which, however, was neither escorted by major changes in the antioxidative defence systems nor was it leading to substantial oxidative damage. Most interestingly, the lowered mitochondrial membrane potential led to a disturbed intramitochondrial calcium homeostasis, which most likely is a major pathomechanism in mitochondrial diseases

  8. Ferroxitosis: A cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma

    Science.gov (United States)

    Lakhter, Alexander J.; Hamilton, James; Dagher, Pierre C.; Mukkamala, Suresh; Hato, Takashi; Dong, X. Charlie; Mayo, Lindsey D.; Harris, Robert A.; Shekhar, Anantha; Ivan, Mircea; Brustovetsky, Nickolay; Naidu, Samisubbu R.

    2014-01-01

    Reliance on glycolysis is a characteristic of malignancy, yet the development of resistance to BRAF inhibitors in melanoma is associated with gain of mitochondrial function. Concurrent attenuation of oxidative phosphorylation and HIF-1α/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen-dependent cell death that we term ferroxitosis. The redox cycling agent menadione causes a robust increase in oxygen consumption, accompanied by significant loss of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of K213Q HIF-1α mutant blunts the effects of menadione. However, knockdown of HIF-1α or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly, exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2 inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions. Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity in melanoma. PMID:25587028

  9. Hepatocellular Toxicity Associated with Tyrosine Kinase Inhibitors: Mitochondrial Damage and Inhibition of Glycolysis

    Directory of Open Access Journals (Sweden)

    Franziska Paech

    2017-06-01

    Full Text Available Tyrosine kinase inhibitors (TKIs are anticancer drugs with a lesser toxicity than classical chemotherapeutic agents but still with a narrow therapeutic window. While hepatotoxicity is known for most TKIs, underlying mechanisms remain mostly unclear. We therefore aimed at investigating mechanisms of hepatotoxicity for imatinib, sunitinib, lapatinib and erlotinib in vitro. We treated HepG2 cells, HepaRG cells and mouse liver mitochondria with TKIs (concentrations 1–100 μM for different periods of time and assessed toxicity. In HepG2 cells maintained with glucose (favoring glycolysis, all TKIs showed a time- and concentration-dependent cytotoxicity and, except erlotinib, a drop in intracellular ATP. In the presence of galactose (favoring mitochondrial metabolism, imatinib, sunitinib and erlotinib showed a similar toxicity profile as for glucose whereas lapatinib was less toxic. For imatinib, lapatinib and sunitinib, cytotoxicity increased in HepaRG cells induced with rifampicin, suggesting formation of toxic metabolites. In contrast, erlotinib was more toxic in HepaRG cells under basal than CYP-induced conditions. Imatinib, sunitinib and lapatinib reduced the mitochondrial membrane potential in HepG2 cells and in mouse liver mitochondria. In HepG2 cells, these compounds increased reactive oxygen species production, impaired glycolysis, and induced apoptosis. In addition, imatinib and sunitinib impaired oxygen consumption and activities of complex I and III (only imatinib, and reduced the cellular GSH pool. In conclusion, imatinib and sunitinib are mitochondrial toxicants after acute and long-term exposure and inhibit glycolysis. Lapatinib affected mitochondria only weakly and inhibited glycolysis, whereas the cytotoxicity of erlotinib could not be explained by a mitochondrial mechanism.

  10. Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment

    Directory of Open Access Journals (Sweden)

    Bo Jiang

    2017-03-01

    Full Text Available Metabolic abnormalities is a hallmark of cancer. About 100 years ago, Nobel laureate Otto Heinrich Warburg first described high rate of glycolysis in cancer cells. Recently more and more novel opinions about cancer metabolism supplement to this hypothesis, consist of glucose uptake, lactic acid generation and secretion, acidification of the microenvironment and cancer immune evasion. Here we briefly review metabolic pathways generating lactate, and discuss the function of higher lactic acid in cancer microenvironments.

  11. Astrocytic energetics during excitatory neurotransmission: What are contributions of glutamate oxidation and glycolysis?

    OpenAIRE

    Dienel, Gerald A.

    2013-01-01

    Astrocytic energetics of excitatory neurotransmission is controversial due to discrepant findings in different experimental systems in vitro and in vivo. The energy requirements of glutamate uptake are believed by some researchers to be satisfied by glycolysis coupled with shuttling of lactate to neurons for oxidation. However, astrocytes increase glycogenolysis and oxidative metabolism during sensory stimulation in vivo, indicating that other sources of energy are used by astrocytes during b...

  12. Neuron-derived transthyretin modulates astrocytic glycolysis in hormone-independent manner

    OpenAIRE

    Zawiślak, Alina; Jakimowicz, Piotr; McCubrey, James A.; Rakus, Dariusz

    2017-01-01

    It has been shown that neurons alter the expression of astrocytic metabolic enzymes by secretion of until now unknown molecule(s) into extracellular fluid. Here, we present evidence that neuron-derived transthyretin (TTR) stimulates expression of glycolytic enzymes in astrocytes which is reflected by an increased synthesis of ATP. The action of TTR is restricted to regulatory enzymes of glycolysis: phosphofructokinase P (PFKP) and pyruvate kinase M1/M2 isoforms (PKM1/2). The regulation of PFK...

  13. High concentrations of H2O2 make aerobic glycolysis energetically more favourable than cellular respiration.

    Directory of Open Access Journals (Sweden)

    Hamid R Molavian

    2016-08-01

    Full Text Available Since the original observation of the Warburg Effect in cancer cells, over eight decades ago, the major question of why aerobic glycolysis is favored over oxidative phosphorylation has remained unresolved. An understanding of this phenomenon may well be the key to the development of more effective cancer therapies. In this paper, we use a semi-empirical method to throw light on this puzzle. We show that aerobic glycolysis is in fact energetically more favorable than oxidative phosphorylation for concentrations of peroxide (H2O2 above some critical threshold value. The fundamental reason for this is the activation and high engagement of the pentose phosphate pathway (PPP in response to the production of reactive oxygen species H2O2 by mitochondria and the high concentration of H2O2 (produced by mitochondria and other sources. This makes oxidative phosphorylation an inefficient source of energy since it leads (despite high levels of ATP production to a concomitant high energy consumption in order to respond to the hazardous waste products resulting from cellular processes associated with this metabolic pathway. We also demonstrate that the high concentration of H2O2 results in an increased glucose consumption, and also increases the lactate production in the case of glycolysis.

  14. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Michelle Barbi de Moura

    Full Text Available SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.

  15. Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility

    Directory of Open Access Journals (Sweden)

    Cara J. Valvona

    2018-03-01

    Full Text Available Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4, which include additional, recently defined subgroups with different prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA is a key enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly observed in cancers, associated with tumour progression and metastasis. Studies indicate MBs have a glycolytic phenotype; however, LDHA has not yet been explored as a therapeutic target for medulloblastoma. LDHA expression was examined in medulloblastoma subgroups and cell lines. The effects of LDHA inhibition by oxamate or LDHA siRNA on medulloblastoma cell line metabolism, migration and proliferation were examined. LDHA was significantly overexpressed in Group 3 and Wnt MBs compared to non-neoplastic cerebellum. Furthermore, we found that oxamate significantly attenuated glycolysis, proliferation and motility in medulloblastoma cell lines, but LDHA siRNA did not. We established that aerobic glycolysis is a potential therapeutic target for medulloblastoma, but broader LDH inhibition (LDHA, B, and C may be more appropriate than LDHA inhibition alone.

  16. Necessity of glycolysis for recovery from ultraviolet killing of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Atsuta, J.; Okajima, S.

    1976-01-01

    An inverse relationship was found between uv (2537 A) survival and preirradiation respiratory rate of diploid yeast: Survival was consistently high in cells grown in anaerobic complete medium where only glycolysis was operating, while it was low in cells grown in aerobic glycerin medium where only oxidative phosphorylation was operating; these observations are consistent with the observed shift from the high resistance in logarithmic phase to the lesser resistance in stationary phase in cells grown in aerobic complete medium. Immediate recovery, which was determined by the ratio between split-dose survival and no recovery survival, occurred only in cells having a low respiratory rate and not in cells having a high respiratory rate. Severe suppression of aerobic ATP synthesis during the first hour after irradiation was found only in cells having a high respiratory rate. Otherwise, delayed recovery, which was determined by immediate plating on glycerin medium, was not related to the respiratory rate. These results indicate a low resistance to uv of oxidative phosphorylation in mitochondria existing at the time of irradiation and a high resistance to uv of both glycolysis and oxidative phosphorylation in new mitochondria produced after irradiation. Survival therefore may be dependent on whether irradiated cells can recover from sublethal damage by utilizing ATP produced by glycolysis immediately after irradiation

  17. Understanding bistability in yeast glycolysis using general properties of metabolic pathways.

    Science.gov (United States)

    Planqué, Robert; Bruggeman, Frank J; Teusink, Bas; Hulshof, Josephus

    2014-09-01

    Glycolysis is the central pathway in energy metabolism in the majority of organisms. In a recent paper, van Heerden et al. showed experimentally and computationally that glycolysis can exist in two states, a global steady state and a so-called imbalanced state. In the imbalanced state, intermediary metabolites accumulate at low levels of ATP and inorganic phosphate. It was shown that Baker's yeast uses a peculiar regulatory mechanism--via trehalose metabolism--to ensure that most yeast cells reach the steady state and not the imbalanced state. Here we explore the apparent bistable behaviour in a core model of glycolysis that is based on a well-established detailed model, and study in great detail the bifurcation behaviour of solutions, without using any numerical information on parameter values. We uncover a rich suite of solutions, including so-called imbalanced states, bistability, and oscillatory behaviour. The techniques employed are generic, directly suitable for a wide class of biochemical pathways, and could lead to better analytical treatments of more detailed models. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer.

    Science.gov (United States)

    Yeung, S J; Pan, J; Lee, M-H

    2008-12-01

    Despite diversity in genetic events in oncogenesis, cancer cells exhibit a common set of functional characteristics. Otto Warburg discovered that cancer cells have consistently higher rates of glycolysis than normal cells. The underlying mechanisms leading to the Warburg phenomenon include mitochondrial changes, upregulation of rate-limiting enzymes/proteins in glycolysis and intracellular pH regulation, hypoxia-induced switch to anaerobic metabolism, and metabolic reprogramming after loss of p53 function. The regulation of energy metabolism can be traced to a "triad" of transcription factors: c-MYC, HIF-1 and p53. Oncogenetic changes involve a nonrandom set of gene deletions, amplifications and mutations, and many oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and interaction with diabetes mellitus. Many drugs targeting energy metabolism are in development. Future advances in technology may bring about transcriptome and metabolome-guided chemotherapy.

  19. Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes.

    Science.gov (United States)

    Winter, Theresa; Hannemann, Anke; Suchsland, Juliane; Nauck, Matthias; Petersmann, Astrid

    2018-03-12

    Measuring the glucose concentration in whole blood samples is critical due to unsatisfactory glycolysis inhibition. Previous studies showed that Terumo tubes were superior, but they were taken off the European market in 2016 and alternatives were required. This initiated the present evaluation of glucose stability in five available tube types. Venous blood samples were collected from 61 healthy volunteers to test tubes supplied by Terumo (two sets), Greiner FC-Mix, BD FX-Mixture and BD serum. After sampling, the contents were thoroughly mixed and centrifuged within an hour. The glucose concentrations were determined and the samples resuspended except for BD serum tubes (gel barrier). The first 30 samples were stored at room temperature and the remaining 31 at 4°C. After 24, 48, 72 and 96 h, all tubes were (re)centrifuged, and glucose concentration measurements were repeated. Changes in glucose concentrations over time differed significantly between the investigated tube types and to a certain extent between the two storing conditions. Glycolysis was most evident in the BD FX-mixture tubes. Good glucose stability was observed in samples retrieved form BD serum and Greiner tubes. The stability in both Terumo tubes was comparable to that in other studies. Although Greiner and both Terumo tubes are supposed to contain the same glycolysis inhibitor, glucose stability differed between these tubes. We showed that Greiner is an acceptable alternative to Terumo and that glucose in serum that was rapidly separated from corpuscles by a gel barrier is stable for an extended time.

  20. Kaempferol inhibits cell proliferation and glycolysis in esophagus squamous cell carcinoma via targeting EGFR signaling pathway.

    Science.gov (United States)

    Yao, Shihua; Wang, Xiaowei; Li, Chunguang; Zhao, Tiejun; Jin, Hai; Fang, Wentao

    2016-08-01

    Antitumor activity of kaempferol has been studied in various tumor types, but its potency in esophagus squamous cell carcinoma is rarely known. Here, we reported the activity of kaempferol against esophagus squamous cell carcinoma as well as its antitumor mechanisms. Results of cell proliferation and colony formation assay showed that kaempferol substantially inhibited tumor cell proliferation and clone formation in vitro. Flow cytometric analysis demonstrated that tumor cells were induced G0/G1 phase arrest after kaempferol treatment, and the expression of protein involved in cell cycle regulation was dramatically changed. Except the potency on cell proliferation, we also discovered that kaempferol had a significant inhibitory effect against tumor glycolysis. With the downregulation of hexokinase-2, glucose uptake and lactate production in tumor cells were dramatically declined. Mechanism studies revealed kaempferol had a direct effect on epidermal growth factor receptor (EGFR) activity, and along with the inhibition of EGFR, its downstream signaling pathways were also markedly suppressed. Further investigations found that exogenous overexpression of EGFR in tumor cells substantially attenuated glycolysis suppression induced by kaempferol, which implied that EGFR also played an important role in kaempferol-mediated glycolysis inhibition. Finally, the antitumor activity of kaempferol was validated in xenograft model and kaempferol prominently restrained tumor growth in vivo. Meanwhile, dramatic decrease of EGFR activity and hexokinase-2 expression were observed in kaempferol-treated tumor tissue, which confirmed these findings in vitro. Briefly, these studies suggested that kaempferol, or its analogues, may serve as effective candidates for esophagus squamous cell carcinoma management.

  1. Simultaneous overexpression of enzymes of the lower part of glycolysis can enhance the fermentative capacity of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Smits, H. P.; Hauf, J.; Muller, S.

    2000-01-01

    Recombinant S. cerevisiae strains, with elevated levels of the enzymes of lower glycolysis (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, phosphoglycerate kinase, enolase, pyruvate kinase, pyruvate decarboxylase and alcohol dehydrogenase) were physiologically characterized...

  2. Mesurements of intracellular ATP provide new insight into the regulation of glycolysis in the yeast Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Ytting, Cecilie Karkov; Fuglsang, Anja Thoe; Hiltunen, J. Kalervo

    2012-01-01

    Glycolysis in the yeast Saccharomyces cerevisiae exhibits temporal oscillation under anaerobic or semianaerobic conditions. Previous evidence indicated that at least two membrane-bound ATPases, the mitochondrial F0F1 ATPase and the plasma membrane P-type ATPase (Pma1p), were important in regulating...... of the temporal behaviour of intracellular ATP in a yeast strain with oscillating glycolysis showed that, in addition to oscillation in intracellular ATP, there is an overall slow decrease in intracellular ATP because the ATP consumption rate exceeds the ATP production in glycolysis. Measurements of the temporal...... activity is under strict control. In the absence of glucose ATPase activity is switched off, and the intracellular ATP concentration is high. When glucose is added to the cells the ATP concentration starts to decrease, because ATP consumption exceeds ATP production by glycolysis. Finally, when glucose...

  3. Histomorphological spetrum of breast lesions.

    Science.gov (United States)

    Parajuli, S; Koirala, U; Khatri, R; Acharya, L; Suwal, A

    2011-04-01

    Cancer of the breast is the second most common cause of cancer in women. Mass in the breast, whether benign or malignant is a cause of anxiety to the patients and the family members. All breast lumps are considered to be carcinomas until proved otherwise and are the causes of concern both for the patient and surgeon. This is a retrospective study conducted in Kathmandu Model Hospital for a total duration of three years from August 2007 to August 2010. 114 sample of breast tissue sent for histopathology were studied. Peak incidence of benign lesion was in between 21-30 years and malignant lesions in between 31-50 years. No breast lesions were seen in the first decade of life. Cancer of the breast was seen in 12.28% of cases. Fibroadenoma and fibrocystic disease were the commonest benign lesion and infiltrating ductal carcinoma was the commonest malignant lesion. Specimens from 10 male breasts were received. Gynaecomastia was the most common lesion encountered in males. Infiltrating ductal carcinoma was seen in a 70 year old male. Breast cancer is one of the commonest causes of breast lump particularly in women and is growing public health problem in Nepal.

  4. Dynamics and regulation of glycolysis-tricarboxylic acid metabolism in the midgut of Spodoptera litura during metamorphosis.

    Science.gov (United States)

    Hu, D; Luo, W; Fan, L F; Liu, F L; Gu, J; Deng, H M; Zhang, C; Huang, L H; Feng, Q L

    2016-04-01

    Significant changes usually take place in the internal metabolism of insects during metamorphosis. The glycolysis-tricarboxylic acid (glycolysis-TCA) pathway is important for energy metabolism. To elucidate its dynamics, the mRNA levels of genes involved in this pathway were examined in the midgut of Spodoptera litura during metamorphosis, and the pyruvate content was quantified. The expression patterns of these genes in response to starvation were examined, and the interaction between protein phosphatase 1 (PP1) and phosphofructokinase (PFK) was studied. The results revealed that the expression or activities of most glycolytic enzymes was down-regulated in prepupae and then recovered in some degree in pupae, and all TCA-related genes were remarkably suppressed in both the prepupae and pupae. Pyruvate was enriched in the pupal midgut. Taken together, these results suggest that insects decrease both glycolysis and TCA in prepupae to save energy and then up-regulate glycolysis but down-regulate TCA in pupae to increase the supply of intermediates for construction of new organs. The expression of all these genes were down-regulated by starvation, indicating that non-feeding during metamorphosis may be a regulator of glycolysis-TCA pathway in the midgut. Importantly, interaction between PP1 and PFK was identified and is suggested to be involved in the regulation of glycolysis. © 2015 The Royal Entomological Society.

  5. Albendazole inhibits HIF-1α-dependent glycolysis and VEGF expression in non-small cell lung cancer cells.

    Science.gov (United States)

    Zhou, Fang; Du, Jin; Wang, Jianjun

    2017-04-01

    Albendazole (ABZ) has an anti-tumor ability and inhibits HIF-1α activity. HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression. These clues indicate that ABZ exerts an anti-cancer effect by regulating glycolysis and VEGF expression. The aim of this study is to clarify the effects of ABZ on non-small cell lung cancer (NSCLC) cells and explore the underlying molecular mechanisms. The expression levels of HIF-1α and VEGF were detected using western blot analysis, and the effect of ABZ on glycolysis was evaluated by measuring the relative activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) and detecting the production of lactate in A549 and H1299 cells. The results showed that ABZ decreased the expression levels of HIF-1α and VEGF and suppressed glycolysis in under hypoxia, but not normoxic condition. Inhibiting HIF-1α also suppressed glycolysis and VEGF expression. Additionally, ABZ inhibited the volume and weight, decreased the relative activities of HK, PK, and LDH, and reduced the levels of HIF-1α and VEGF of A549 xenografts in mouse models. In conclusion, ABZ inhibited growth of NSCLC cells by suppressing HIF-1α-dependent glycolysis and VEGF expression.

  6. Succinyl-proteome profiling of Dendrobium officinale, an important traditional Chinese orchid herb, revealed involvement of succinylation in the glycolysis pathway.

    Science.gov (United States)

    Feng, Shangguo; Jiao, Kaili; Guo, Hong; Jiang, Mengyi; Hao, Juan; Wang, Huizhong; Shen, Chenjia

    2017-08-10

    Lysine succinylation is a ubiquitous and important protein post-translational modification in various eukaryotic and prokaryotic cells. However, its functions in Dendrobium officinale, an important traditional Chinese orchid herb with high polysaccharide contents, are largely unknown. In our study, LC-MS/MS was used to identify the peptides that were enriched by immune-purification with a high-efficiency succinyl-lysine antibody. In total, 314 lysine succinylation sites in 207 proteins were identified. A gene ontology analysis showed that these proteins are associated with a wide range of cellular functions, from metabolic processes to stimuli responses. Moreover, two types of conserved succinylation motifs, '***K suc ******K**' and '****EK suc ***', were identified. Our data showed that lysine succinylation occurred on five key enzymes in the glycolysis pathway. The numbers of average succinylation sites on these five enzymes in plants were lower than those in bacteria and mammals. Interestingly, two active site amino acids residues, K103 and K225, could be succinylated in fructose-bisphosphate aldolase, indicating a potential function of lysine succinylation in the regulation of glycolytic enzyme activities. Furthermore, the protein-protein interaction network for the succinylated proteins showed that several functional terms, such as glycolysis, TCA cycle, oxidative phosphorylation and ribosome, are consisted. Our results provide the first comprehensive view of the succinylome of D. officinale and may accelerate future biological investigations of succinylation in the synthesis of polysaccharides, which are major active ingredients.

  7. Oropharynx lesion biopsy

    Science.gov (United States)

    ... as papilloma) Fungal infections (such as candida) Histoplasmosis Oral lichen planus Precancerous sore (leukoplakia) Viral infections (such as Herpes simplex) Risks Risks of the procedure may ... Throat lesion biopsy; Biopsy - mouth or throat; Mouth lesion biopsy; Oral cancer - biopsy ...

  8. Managing Carious Lesions

    DEFF Research Database (Denmark)

    Schwendicke, F; Frencken, J E; Bjørndal, L

    2016-01-01

    should be prioritized, while in shallow or moderately deep lesions, restoration longevity becomes more important. For teeth with shallow or moderately deep cavitated lesions, carious tissue removal is performed according toselective removal to firm dentine.In deep cavitated lesions in primary......The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental...

  9. The miR-383-LDHA axis regulates cell proliferation, invasion and glycolysis in hepatocellular cancer

    Directory of Open Access Journals (Sweden)

    Zhixiong Fang

    2017-02-01

    Full Text Available Objective(s: To explore the correlation between expression patterns and functions of miR-383 and LDHA in hepatocellular cancer (HCC. Materials and Methods: We detected the expression of miR-383 and LDHA in 30 HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-383 in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-383. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-383. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-383. Results: The results of qRT-PCR showed that miR-383 was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-383 significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-383 and expression of LDHA was inversely correlated with that of miR-383 in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-383 in HCC cell lines. Conclusion: Our study proved that miR-383 is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-383-LDHA axis might be a promising strategy in HCC treatment.

  10. The nutritional status of Methanosarcina acetivorans regulates glycogen metabolism and gluconeogenesis and glycolysis fluxes.

    Science.gov (United States)

    Santiago-Martínez, Michel Geovanni; Encalada, Rusely; Lira-Silva, Elizabeth; Pineda, Erika; Gallardo-Pérez, Juan Carlos; Reyes-García, Marco Antonio; Saavedra, Emma; Moreno-Sánchez, Rafael; Marín-Hernández, Alvaro; Jasso-Chávez, Ricardo

    2016-05-01

    Gluconeogenesis is an essential pathway in methanogens because they are unable to use exogenous hexoses as carbon source for cell growth. With the aim of understanding the regulatory mechanisms of central carbon metabolism in Methanosarcina acetivorans, the present study investigated gene expression, the activities and metabolic regulation of key enzymes, metabolite contents and fluxes of gluconeogenesis, as well as glycolysis and glycogen synthesis/degradation pathways. Cells were grown with methanol as a carbon source. Key enzymes were kinetically characterized at physiological pH/temperature. Active consumption of methanol during exponential cell growth correlated with significant methanogenesis, gluconeogenic flux and steady glycogen synthesis. After methanol exhaustion, cells reached the stationary growth phase, which correlated with the rise in glycogen consumption and glycolytic flux, decreased methanogenesis, negligible acetate production and an absence of gluconeogenesis. Elevated activities of carbon monoxide dehydrogenase/acetyl-CoA synthetase complex and pyruvate: ferredoxin oxidoreductase suggested the generation of acetyl-CoA and pyruvate for glycogen synthesis. In the early stationary growth phase, the transcript contents and activities of pyruvate phosphate dikinase, fructose 1,6-bisphosphatase and glycogen synthase decreased, whereas those of glycogen phosphorylase, ADP-phosphofructokinase and pyruvate kinase increased. Therefore, glycogen and gluconeogenic metabolites were synthesized when an external carbon source was provided. Once such a carbon source became depleted, glycolysis and methanogenesis fed by glycogen degradation provided the ATP supply. Weak inhibition of key enzymes by metabolites suggested that the pathways evaluated were mainly transcriptionally regulated. Because glycogen metabolism and glycolysis/gluconeogenesis are not present in all methanogens, the overall data suggest that glycogen storage might represent an environmental

  11. HSulf-1 deficiency dictates a metabolic reprograming of glycolysis and TCA cycle in ovarian cancer.

    Science.gov (United States)

    Mondal, Susmita; Roy, Debarshi; Camacho-Pereira, Juliana; Khurana, Ashwani; Chini, Eduardo; Yang, Lifeng; Baddour, Joelle; Stilles, Katherine; Padmabandu, Seth; Leung, Sam; Kalloger, Steve; Gilks, Blake; Lowe, Val; Dierks, Thomas; Hammond, Edward; Dredge, Keith; Nagrath, Deepak; Shridhar, Viji

    2015-10-20

    Warburg effect has emerged as a potential hallmark of many cancers. However, the molecular mechanisms that led to this metabolic state of aerobic glycolysis, particularly in ovarian cancer (OVCA) have not been completely elucidated. HSulf-1 predominantly functions by limiting the bioavailability of heparan binding growth factors and hence their downstream signaling. Here we report that HSulf-1, a known putative tumor suppressor, is a negative regulator of glycolysis. Silencing of HSulf-1 expression in OV202 cell line increased glucose uptake and lactate production by upregulating glycolytic genes such as Glut1, HKII, LDHA, as well as metabolites. Conversely, HSulf-1 overexpression in TOV21G cells resulted in the down regulation of glycolytic enzymes and reduced glycolytic phenotype, supporting the role of HSulf-1 loss in enhanced aerobic glycolysis. HSulf-1 deficiency mediated glycolytic enhancement also resulted in increased inhibitory phosphorylation of pyruvate dehydrogenase (PDH) thus blocking the entry of glucose flux into TCA cycle. Consistent with this, metabolomic and isotope tracer analysis showed reduced glucose flux into TCA cycle. Moreover, HSulf-1 loss is associated with lower oxygen consumption rate (OCR) and impaired mitochondrial function. Mechanistically, lack of HSulf-1 promotes c-Myc induction through HB-EGF-mediated p-ERK activation. Pharmacological inhibition of c-Myc reduced HB-EGF induced glycolytic enzymes implicating a major role of c-Myc in loss of HSulf-1 mediated altered glycolytic pathway in OVCA. Similarly, PG545 treatment, an agent that binds to heparan binding growth factors and sequesters growth factors away from their ligand also blocked HB-EGF signaling and reduced glucose uptake in vivo in HSulf-1 deficient cells.

  12. Sensitivity analysis of the noise-induced oscillatory multistability in Higgins model of glycolysis

    Science.gov (United States)

    Ryashko, Lev

    2018-03-01

    A phenomenon of the noise-induced oscillatory multistability in glycolysis is studied. As a basic deterministic skeleton, we consider the two-dimensional Higgins model. The noise-induced generation of mixed-mode stochastic oscillations is studied in various parametric zones. Probabilistic mechanisms of the stochastic excitability of equilibria and noise-induced splitting of randomly forced cycles are analysed by the stochastic sensitivity function technique. A parametric zone of supersensitive Canard-type cycles is localized and studied in detail. It is shown that the generation of mixed-mode stochastic oscillations is accompanied by the noise-induced transitions from order to chaos.

  13. Activation of glycolysis and inhibition of glucose transport into leaves by fluoride

    Energy Technology Data Exchange (ETDEWEB)

    Lustinec, J; Pokorna, V; Ruzicka, J

    1962-01-01

    During stimulation of wheat leaf respiration by fluoride at 100 to 200 ppM fluorine in dry tissue the ratio of radioactivities of /sup 14/CO/sub 2/ released from glucose-6-/sup 14/C and that released from glucose-1-/sup 14/C (C/sub 6//C/sub 1/) increases due especially to an increased output of 6-/sup 14/CO/sub 2/ which suggests an activation of glycolysis. The absolute values of radioactivity of /sup 14/CO/sub 2/, however, are decreased by the action of fluoride due to its inhibition of the transport of glucose into leaves. 15 references, 2 figures, 2 tables.

  14. A HISTOPATHOLOGICAL SPECTRUM OF NECK LESIONS IN A RURAL HOSPITAL

    Directory of Open Access Journals (Sweden)

    Shri Lakshmi Surapaneni

    2016-07-01

    Full Text Available BACKGROUND A multitude of lesions occur in the neck and patients come to hospital on account of morbidity associated with these lesions. Therefore a histopathological study of the spectrum of neck lesions was undertaken. MATERIALS AND METHODS All histologically diagnosed lesions of the neck from January 2014 to December 2015 were noted. Details of gender, age, location and diagnosis were recorded. The lesions were classified based on anatomic location, gross and histological features and clinically. Clinically, lesions were classified as congenital, inflammatory/infective and neoplastic. Incidence of age, gender and location of different lesions was calculated using percentage, and median. The findings were compared with other studies. RESULTS A total of 140 neck lesions were included in the current study. Neck lesions were predominant in females with 94 cases. The median age group involved was the 21-30 group. Anterior neck lesions were more common. Anterior midline lesions were 74 and mostly thyroid and thyroglossal duct origin. Lesions of the lymph node were greater in the posterior triangle. 122 lesions were solid and 18 were cystic. Histologically, there were 64 thyroid gland lesions, 40 lymph node lesions, 13 soft tissue tumours, 8 salivary lesions, 10 thyroglossal cysts and 5 skin/adnexal lesions. Clinically, congenital/developmental lesions were 11, inflammatory/infective lesions were 68 and neoplastic lesions were 61. Of the neoplastic lesions, 17 were malignant. CONCLUSION Non-neoplastic lesions of the neck were common in our study in accordance with findings in other studies. The most common malignancy was Papillary carcinoma of thyroid.

  15. EPR oxygen imaging and hyperpolarized (13) C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    DEFF Research Database (Denmark)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu

    2013-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has...... the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under...

  16. Periodontal bone lesions

    International Nuclear Information System (INIS)

    Linden, L.W.J. van der.

    1985-01-01

    In the course of life the periodontum is subject to changes which may be physiological or pathological. Intraoral radiographs give insight into the hard structures of the dentomaxillar region and provides information on lesions in the bone of the periodontum in that they show radiopacities and radiolucencies caused by such lesions. In this thesis the relation is investigated between the true shape and dimensions of periodontal bone lesions and their radiographic images. A method is developed and tested of making standardized and reproducible radiographs suitable for longitudinal studies of periodontal lesions. Also the possibility is demonstrated of an objective and reproducible interpretation of radiographic characteristics of periodontal bone lesions. (Auth.)

  17. Large Intergenic Non-coding RNA-RoR Inhibits Aerobic Glycolysis of Glioblastoma Cells via Akt Pathway

    Science.gov (United States)

    Li, Yong; He, Zhi-Cheng; Liu, Qing; Zhou, Kai; Shi, Yu; Yao, Xiao-Hong; Zhang, Xia; Kung, Hsiang-Fu; Ping, Yi-Fang; Bian, Xiu-Wu

    2018-01-01

    Reprogramming energy metabolism is a hallmark of malignant tumors, including glioblastoma (GBM). Aerobic glycolysis is often utilized by tumor cells to maintain survival and proliferation. However, the underlying mechanisms of aerobic glycolysis in GBM remain elusive. Herein, we demonstrated that large intergenic non-coding RNA-RoR (LincRNA-RoR) functioned as a critical suppressor to inhibit the aerobic glycolysis and viability of GBM cells. We found that LincRNA-RoR was markedly reduced in GBM tissues compared with adjacent non-tumor tissues from 10 cases of GBM patients. Consistently, LincRNA-RoR expression in GBM cells was significantly lower than that in normal glial cells. The aerobic glycolysis of GBM cells, as determined by the measurement of glucose uptake and lactate production, was impaired by LincRNA-RoR overexpression. Mechanistically, LincRNA-RoR inhibited the expression of Rictor, the key component of mTORC2 (mammalian target of rapamycin complex 2), to suppress the activity of Akt pathway and impair the expression of glycolytic effectors, including Glut1, HK2, PKM2 and LDHA. Finally, enforced expression of LincRNA-RoR reduced the proliferation of GBM cells in vitro, restrained tumor growth in vivo, and repressed the expression of glycolytic molecules in GBM xenografts. Collectively, our results underscore LincRNA-RoR as a new suppressor of GBM aerobic glycolysis with therapeutic potential. PMID:29581766

  18. Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis

    Science.gov (United States)

    Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F.; Lane, Andrew N.; Romick-Rosendale, Lindsey E.; Wells, Susanne I.

    2017-01-01

    The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth. PMID:28558019

  19. Glycolysis of carbon fiber-epoxy unidirectional mat catalysed by sodium hydroxide

    Science.gov (United States)

    Zaini, Mariana Binti Mohd; Badri, Khairiah Haji

    2014-09-01

    This study was conducted to recycle carbon fibre-epoxy (CFRP) composite in woven sheet/ mat form. The CFRP was recycled through glycolysis with polyethlyene glycol (PEG 200) as the solvent. The CFRP was loaded into the solvent at a ratio of 4:1 (w/w). PEG200 was diluted with water to a ratio of 80:20 (v/v). This reaction was catalysed by sodium hydroxide (NaOH) solution with varying concentrations at 1.5, 1.7 and 1.9% (w/v). The glycolysis was conducted at 180-190 °C. The recovered CF (rCF) was analysed using Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray (EDX) while the degraded solution was analysed using FTIR and the epoxy content was determined. The FTIR spectrum of the rCF exhibited the disappearance of the COC peak belonged to epoxy and supported by the SEM micrographs that showed clear rCF. On the other hand, the analysed filtrate detected the disappearance of oxygen peak element in the EDX spectrum for all rCF samples. This gave an indication that the epoxy resin has been removed from the surface of the carbon fiber.

  20. LMP1-mediated glycolysis induces myeloid-derived suppressor cell expansion in nasopharyngeal carcinoma.

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    Ting-Ting Cai

    2017-07-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV-associated nasopharyngeal carcinoma (NPC. The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1 promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1 and CD33+ MDSCs in tumor sections. The full process has been reconstituted in vitro. LMP1 promotes the expression of multiple glycolytic genes, including GLUT1. This metabolic reprogramming results in increased expression of the Nod-like receptor family protein 3 (NLRP3 inflammasome, COX-2 and P-p65 and, consequently, increased production of IL-1β, IL-6 and GM-CSF. Finally, these changes in the environment of malignant cells result in enhanced NPC-derived MDSC induction. One key step is the physical interaction of LMP1 with GLUT1 to stabilize the GLUT1 protein by blocking its K48-ubiquitination and p62-dependent autolysosomal degradation. This work indicates that LMP1-mediated glycolysis regulates IL-1β, IL-6 and GM-CSF production through the NLRP3 inflammasome, COX-2 and P-p65 signaling pathways to enhance tumor-associated MDSC expansion, which leads to tumor immunosuppression in NPC.

  1. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    Science.gov (United States)

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2015-02-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro . However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

  2. Glycolysis in Panc-1 human pancreatic cancer cells is inhibited by everolimus.

    Science.gov (United States)

    Liu, Ling; Gong, Liansheng; Zhang, Yangde; Li, Nianfeng

    2013-01-01

    The aim of this study was to evaluate the effects and molecular mechanisms of everolimus on Panc-1 human pancreatic cancer cells. Panc-1 human pancreatic cancer cells were treated with everolimus (10 μg/ml) at selected time points (6, 12 and 24 h). Cell proliferation and apoptosis were evaluated by MTT and flow cytometric analyses. The glycolytic activity was determined by measuring the activity of the key enzyme lactate dehydrogenase (LDH) and lactate production. The activity of mammalian target of rapamycin (mTOR) signaling was measured by western blotting. The expression of genes, including hexokinase 2 (HK2) and microRNA-143 (miR-143), was evaluated by real-time polymerase chain reaction (PCR). The administration of everolimus time-dependently inhibited proliferation and glycolysis and induced apoptosis in the Panc-1 human pancreatic cancer cells. As the time of treatment with everolimus increased, the mTOR signaling activity decreased, indicated by lower phosphorylation levels of S6 kinase; however, the phosphorylation levels of mTOR barely changed. Moreover, our data showed an everolimus-induced increase in miR-143 and decrease in HK2 in Panc-1 cells in a time-dependent manner. In conclusion, the current study indicates a novel role of everolimus in its antitumor effect as an inhibitor of glycolysis in Panc-1 human pancreatic cancer cells. Furthermore, our data highlights the significance of exploring the mechanisms of everolimus and miR-143 in malignant tumors.

  3. Glycolysis of carbon fiber-epoxy unidirectional mat catalysed by sodium hydroxide

    Energy Technology Data Exchange (ETDEWEB)

    Zaini, Mariana Binti Mohd [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor (Malaysia); Badri, Khairiah Haji [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia and Polymer Research Center, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43 (Malaysia)

    2014-09-03

    This study was conducted to recycle carbon fibre-epoxy (CFRP) composite in woven sheet/ mat form. The CFRP was recycled through glycolysis with polyethlyene glycol (PEG 200) as the solvent. The CFRP was loaded into the solvent at a ratio of 4:1 (w/w). PEG200 was diluted with water to a ratio of 80:20 (v/v). This reaction was catalysed by sodium hydroxide (NaOH) solution with varying concentrations at 1.5, 1.7 and 1.9% (w/v). The glycolysis was conducted at 180-190 °C. The recovered CF (rCF) was analysed using Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-Ray (EDX) while the degraded solution was analysed using FTIR and the epoxy content was determined. The FTIR spectrum of the rCF exhibited the disappearance of the COC peak belonged to epoxy and supported by the SEM micrographs that showed clear rCF. On the other hand, the analysed filtrate detected the disappearance of oxygen peak element in the EDX spectrum for all rCF samples. This gave an indication that the epoxy resin has been removed from the surface of the carbon fiber.

  4. Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation.

    Science.gov (United States)

    Jackson, Laura E; Kulkarni, Sucheta; Wang, Huabo; Lu, Jie; Dolezal, James M; Bharathi, Sivakama S; Ranganathan, Sarangarajan; Patel, Mulchand S; Deshpande, Rahul; Alencastro, Frances; Wendell, Stacy G; Goetzman, Eric S; Duncan, Andrew W; Prochownik, Edward V

    2017-11-01

    Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC "knockout" (KO) animals, the long-term regenerative potential of hepatocytes was unimpaired, and growth of aggressive experimental hepatoblastomas was only modestly slowed in the face of 80%-90% reductions in AcCoA and significant alterations in the levels of key tricarboxylic acid (TCA) cycle intermediates and amino acids. Overall, oxphos activity in KO livers and hepatoblastoma was comparable with that of control counterparts, with evidence that metabolic substrate abnormalities were compensated for by increased mitochondrial mass. These findings demonstrate that the biochemical link between glycolysis and the TCA cycle can be completely severed without affecting normal or neoplastic proliferation, even under the most demanding circumstances. Cancer Res; 77(21); 5795-807. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

    Directory of Open Access Journals (Sweden)

    Marie C Matrka

    Full Text Available The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos. To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

  6. Influence of Cooling on the Glycolysis Rate and Development of PSE (Pale, Soft, Exudative Meat

    Directory of Open Access Journals (Sweden)

    Mayka Reghiany Pedrão

    2015-04-01

    Full Text Available The aim of this work was to evaluate pH values fall rate in chicken breast meat under commercial refrigeration processing conditions and the development of PSE (pale, soft, exudative meat. Broiler breast samples from the Cobb breed, both genders, at 47 days of age (n = 100 were taken from refrigerated carcasses (RS immersed in water and ice in a tank chilled at 0°C (±2. pH and temperature (T values were recorded at several periods throughout refrigeration in comparison to samples left at room T as control (CS. The ultimate pH (pHu value of 5.86 for RS carcasses were only reached at 11°C after 8.35 h post mortem (PM while, for CS samples, pHu value was 5.94 at 22°C after 4.08 h PM. Thus, under commercial refrigeration conditions, the glycolysis rate was retarded by over 4.0 h PM and the breast meat color was affected. At 24.02 h PM, PSE meat incidence was 30% while for CS, meat remained dark and PSE meat was not detected. Results show retardation in the glycolysis rate and PSE meat development was promoted by the refrigeration treatment when compared with samples stored at processing room temperature.

  7. Emerging Glycolysis Targeting and Drug Discovery from Chinese Medicine in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Zhiyu Wang

    2012-01-01

    Full Text Available Molecular-targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells have different metabolic properties from normal cells. Normal cells mostly rely upon the process of mitochondrial oxidative phosphorylation to produce energy whereas cancer cells have developed an altered metabolism that allows them to sustain higher proliferation rates. Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM is recognized as a valuable source for seeking bioactive anticancer compounds. A great progress has been made to identify active compounds from herbal medicine targeting on glycolysis for cancer treatment. Herein, we provide an overall picture of the current understanding of the molecular targets in the cancer glycolytic pathway and reviewed active compounds from Chinese herbal medicine with the potentials to inhibit the metabolic targets for cancer treatment. Combination of TCM with conventional therapies will provide an attractive strategy for improving clinical outcome in cancer treatment.

  8. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation.

    Science.gov (United States)

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-06-10

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size.

  9. Glycolysis of poly (3-hydroxybutyrate) catalyzed by an enzyme system; Glicolise do poli(3-hidroxibutirato) por via enzimatica

    Energy Technology Data Exchange (ETDEWEB)

    Campos, T.F.; Mano, V., E-mail: mano@ufsj.edu.b [Universidade Federal de Sao Joao del Rei (UFSJ), MG (Brazil). Dept. de Ciencias Naturais

    2010-07-01

    In this work we report the studies of PHB glycolysis catalyzed by lipase Amano PS (Pseudomonas cepacia) in the presence of 1,2-ethanediol (ethylene glycol). The reactions were performed in toluene:dichloroethane 3:1 (v/v) at 60 deg C, varying reaction time and concentration of ethylene glycol. PHB and the products of glycolysis (polyols) were characterized by FTIR, {sup 1}H-NMR, and TG. The FTIR spectra of polyols showed no significant change compared to the spectrum of PHB. The {sup 1}H-NMR spectra of the products of glycolysis showed signs of interest between 3 and 4.7 ppm, related to the ethylene glycol protons inserted in the polymer chain. By analyzing the thermograms we observed that the polyols are more thermally stable than PHB. (author)

  10. Functional importance of the astrocytic glycogen-shunt and glycolysis for maintenance of an intact intra/extracellular glutamate gradient

    DEFF Research Database (Denmark)

    Schousboe, Arne; Sickmann, Helle M; Walls, Anne B

    2010-01-01

    It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate. The impo......It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate....... The importance of this as well as the significance of ATP formed in glycolysis versus that formed by the concerted action of the tricarboxylic acid (TCA) cycle processes and oxidative phosphorylation for maintenance of glutamate transport capacity in astrocytes is discussed. It is argued that glycolytically...

  11. miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Yaguang; Cheng, Chuanyao; Lu, Hong, E-mail: honglu6512@163.com; Wang, Yaqiu

    2016-01-01

    miR-4458, a new tumor-suppressor, was reported to down-regulated in human hepatocellular carcinoma. The expression status, roles and inhibitory mechanisms of miR-4458 in other tumors still need to be clarified. The aim of this study is to investigate the effects of miR-4458 and to elucidate the potential mechanism in colon cancer cells. Using bioinformatic databases, we predicted that hexokinase2 (HK2), a rate-limiting enzyme in the glycolytic pathway, was a target of miR-4458, so the effects of miR-4458 on glycolysis and lactate production was assessed in colon cancer cells. We found that miR-4458 was down-regulated and HK2 was up-regulated in colon cancer cells. Overexpression of miR-4458 inhibited proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. Luciferase activity assays showed that HK2 was a direct target of miR-4458. Moreover, knockdown of HK2 by specific RNAi also suppressed proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. In conclusion, our findings suggested that miR-4458 inhibited the progression of colon cancer cells by inhibition of glycolysis and lactate production via directly targeting HK2 mRNA. - Highlights: • miR-4458 is down-regulated in colon cancer cells. • miR-4458 suppresses proliferation, glycolysis, and lactate production. • HK2 is a target of miR-4458. • HK2 knockdown inhibits proliferation, glycolysis, and lactate production.

  12. Expression of genes encoding F-1-ATPase results in uncoupling of glycolysis from biomass production in Lactococcus lactis

    DEFF Research Database (Denmark)

    Købmann, Brian Jensen; Solem, Christian; Pedersen, M.B.

    2002-01-01

    of the genes encoding F-1-ATPase was found to decrease the intracellular energy level and resulted in a decrease in the growth rate. The yield of biomass also decreased, which showed that the incorporated F-1-ATPase activity caused glycolysis to be uncoupled from biomass production. The increase in ATPase...... threefold in nongrowing cells resuspended in buffer, but in steadily growing cells no increase in flux was observed. The latter result shows that glycolysis occurs close to its maximal capacity and indicates that control of the glycolytic flux under these conditions resides in the glycolytic reactions...

  13. Ghost cell lesions

    Directory of Open Access Journals (Sweden)

    E Rajesh

    2015-01-01

    Full Text Available Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms.

  14. E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Jennifer L Major

    Full Text Available The E2F pathway plays a critical role in cardiac growth and development, yet its role in cardiac metabolism remains to be defined. Metabolic changes play important roles in human heart failure and studies imply the ketogenic enzyme β-hydroxybutyrate dehydrogenase I (BDH1 is a potential biomarker.To define the role of the E2F pathway in cardiac metabolism and dilated cardiomyopathy (DCM with a focus on BDH1.We previously developed transgenic (Tg mice expressing the transcriptional repressor, E2F6, to interfere with the E2F/Rb pathway in post-natal myocardium. These Tg mice present with an E2F6 dose dependent DCM and deregulated connexin-43 (CX-43 levels in myocardium. Using the Seahorse platform, a 22% decrease in glycolysis was noted in neonatal cardiomyocytes isolated from E2F6-Tg hearts. This was associated with a 39% reduction in the glucose transporter GLUT4 and 50% less activation of the regulator of glucose metabolism AKT2. The specific reduction of cyclin B1 (70% in Tg myocardium implicates its importance in supporting glycolysis in the postnatal heart. No changes in cyclin D expression (known to regulate mitochondrial activity were noted and lipid metabolism remained unchanged in neonatal cardiomyocytes from Tg hearts. However, E2F6 induced a 40-fold increase of the Bdh1 transcript and 890% increase in its protein levels in hearts from Tg pups implying a potential impact on ketolysis. By contrast, BDH1 expression is not activated until adulthood in normal myocardium. Neonatal cardiomyocytes from Wt hearts incubated with the ketone β-hydroxybutyrate (β-OHB showed a 100% increase in CX-43 protein levels, implying a role for ketone signaling in gap junction biology. Neonatal cardiomyocyte cultures from Tg hearts exhibited enhanced levels of BDH1 and CX-43 and were not responsive to β-OHB.The data reveal a novel role for the E2F pathway in regulating glycolysis in the developing myocardium through a mechanism involving cyclin B1. We

  15. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  16. Juxtacortical Lesions and Cortical Thinning in Multiple Sclerosis.

    Science.gov (United States)

    Pareto, D; Sastre-Garriga, J; Auger, C; Vives-Gilabert, Y; Delgado, J; Tintoré, M; Montalban, X; Rovira, A

    2015-12-01

    The role of juxtacortical lesions in brain volume loss in multiple sclerosis has not been fully clarified. The aim of this study was to explore the role of juxtacortical lesions on cortical atrophy and to investigate whether the presence of juxtacortical lesions is related to local cortical thinning in the early stages of MS. A total of 131 patients with clinically isolated syndrome or with relapsing-remitting MS were scanned on a 3T system. Patients with clinically isolated syndrome were classified into 3 groups based on the presence and topography of brain lesions: no lesions (n = 24), only non-juxtacortical lesions (n = 33), and juxtacortical lesions and non-juxtacortical lesions (n = 34). Patients with relapsing-remitting MS were classified into 2 groups: only non-juxtacortical lesions (n = 10) and with non-juxtacortical lesions and juxtacortical lesions (n = 30). A juxtacortical lesion probability map was generated, and cortical thickness was measured by using FreeSurfer. Juxtacortical lesion volume in relapsing-remitting MS was double that of patients with clinically isolated syndrome. The insula showed the highest density of juxtacortical lesions, followed by the temporal, parietal, frontal, and occipital lobes. Patients with relapsing-remitting MS with juxtacortical lesions showed significantly thinner cortices overall and in the parietal and temporal lobes compared with those with clinically isolated syndrome with normal brain MR imaging. The volume of subcortical structures (thalamus, pallidum, putamen, and accumbens) was significantly decreased in relapsing-remitting MS with juxtacortical lesions compared with clinically isolated syndrome with normal brain MR imaging. The spatial distribution of juxtacortical lesions was not found to overlap with areas of cortical thinning. Cortical thinning and subcortical gray matter volume loss in patients with a clinically isolated syndrome or relapsing-remitting MS was related to the presence of juxtacortical

  17. The transcriptional co-repressor myeloid translocation gene 16 inhibits glycolysis and stimulates mitochondrial respiration.

    Directory of Open Access Journals (Sweden)

    Parveen Kumar

    Full Text Available The myeloid translocation gene 16 product MTG16 is found in multiple transcription factor-containing complexes as a regulator of gene expression implicated in development and tumorigenesis. A stable Tet-On system for doxycycline-dependent expression of MTG16 was established in B-lymphoblastoid Raji cells to unravel its molecular functions in transformed cells. A noticeable finding was that expression of certain genes involved in tumor cell metabolism including 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4 (PFKFB3 and PFKFB4, and pyruvate dehydrogenase kinase isoenzyme 1 (PDK1 was rapidly diminished when MTG16 was expressed. Furthermore, hypoxia-stimulated production of PFKFB3, PFKFB4 and PDK1 was inhibited by MTG16 expression. The genes in question encode key regulators of glycolysis and its coupling to mitochondrial metabolism and are commonly found to be overexpressed in transformed cells. The MTG16 Nervy Homology Region 2 (NHR2 oligomerization domain and the NHR3 protein-protein interaction domain were required intact for inhibition of PFKFB3, PFKFB4 and PDK1 expression to occur. Expression of MTG16 reduced glycolytic metabolism while mitochondrial respiration and formation of reactive oxygen species increased. The metabolic changes were paralleled by increased phosphorylation of mitogen-activated protein kinases, reduced levels of amino acids and inhibition of proliferation with a decreased fraction of cells in S-phase. Overall, our findings show that MTG16 can serve as a brake on glycolysis, a stimulator of mitochondrial respiration and an inhibitor of cell proliferation. Hence, elevation of MTG16 might have anti-tumor effect.

  18. Quantitative elementary mode analysis of metabolic pathways: the example of yeast glycolysis

    Directory of Open Access Journals (Sweden)

    Kanehisa Minoru

    2006-04-01

    Full Text Available Abstract Background Elementary mode analysis of metabolic pathways has proven to be a valuable tool for assessing the properties and functions of biochemical systems. However, little comprehension of how individual elementary modes are used in real cellular states has been achieved so far. A quantitative measure of fluxes carried by individual elementary modes is of great help to identify dominant metabolic processes, and to understand how these processes are redistributed in biological cells in response to changes in environmental conditions, enzyme kinetics, or chemical concentrations. Results Selecting a valid decomposition of a flux distribution onto a set of elementary modes is not straightforward, since there is usually an infinite number of possible such decompositions. We first show that two recently introduced decompositions are very closely related and assign the same fluxes to reversible elementary modes. Then, we show how such decompositions can be used in combination with kinetic modelling to assess the effects of changes in enzyme kinetics on the usage of individual metabolic routes, and to analyse the range of attainable states in a metabolic system. This approach is illustrated by the example of yeast glycolysis. Our results indicate that only a small subset of the space of stoichiometrically feasible steady states is actually reached by the glycolysis system, even when large variation intervals are allowed for all kinetic parameters of the model. Among eight possible elementary modes, the standard glycolytic route remains dominant in all cases, and only one other elementary mode is able to gain significant flux values in steady state. Conclusion These results indicate that a combination of structural and kinetic modelling significantly constrains the range of possible behaviours of a metabolic system. All elementary modes are not equal contributors to physiological cellular states, and this approach may open a direction toward a

  19. Quantitative analysis of glycerol accumulation, glycolysis and growth under hyper osmotic stress.

    Directory of Open Access Journals (Sweden)

    Elzbieta Petelenz-Kurdziel

    Full Text Available We provide an integrated dynamic view on a eukaryotic osmolyte system, linking signaling with regulation of gene expression, metabolic control and growth. Adaptation to osmotic changes enables cells to adjust cellular activity and turgor pressure to an altered environment. The yeast Saccharomyces cerevisiae adapts to hyperosmotic stress by activating the HOG signaling cascade, which controls glycerol accumulation. The Hog1 kinase stimulates transcription of genes encoding enzymes required for glycerol production (Gpd1, Gpp2 and glycerol import (Stl1 and activates a regulatory enzyme in glycolysis (Pfk26/27. In addition, glycerol outflow is prevented by closure of the Fps1 glycerol facilitator. In order to better understand the contributions to glycerol accumulation of these different mechanisms and how redox and energy metabolism as well as biomass production are maintained under such conditions we collected an extensive dataset. Over a period of 180 min after hyperosmotic shock we monitored in wild type and different mutant cells the concentrations of key metabolites and proteins relevant for osmoadaptation. The dataset was used to parameterize an ODE model that reproduces the generated data very well. A detailed computational analysis using time-dependent response coefficients showed that Pfk26/27 contributes to rerouting glycolytic flux towards lower glycolysis. The transient growth arrest following hyperosmotic shock further adds to redirecting almost all glycolytic flux from biomass towards glycerol production. Osmoadaptation is robust to loss of individual adaptation pathways because of the existence and upregulation of alternative routes of glycerol accumulation. For instance, the Stl1 glycerol importer contributes to glycerol accumulation in a mutant with diminished glycerol production capacity. In addition, our observations suggest a role for trehalose accumulation in osmoadaptation and that Hog1 probably directly contributes to the

  20. Lesion activity assessment

    DEFF Research Database (Denmark)

    Ekstrand, K R; Zero, D T; Martignon, S

    2009-01-01

    in response to cariogenic plaque as well as lesion arrest. Based on this understanding, different clinical scoring systems have been developed to assess the severity/depth and activity of lesions. A recent system has been devised by the International Caries Detection and Assessment System Committee...

  1. Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enxymes? Testing biochemistry.

    NARCIS (Netherlands)

    Teusink, B.; Passarge, J.R.; Reijenga, C.A.; Esgalhado, M.E.L.M.; van der Weijden, C.C.; Schepper, M.; Walsh, M.C.; Bakker, B.M.; van Dam, K.; Westerhoff, H.V.; Snoep, J.L.

    2000-01-01

    This paper examines whether the in vivo behavior of yeast glycolysis can be understood in terms of the in vitro kinetic properties of the constituent enzymes. In nongrowing, anaerobic, compressed Saccharomyces cerevisiae the values of the kinetic parameters of most glycolytic enzymes were

  2. Preslaughter Transport Effect on Broiler Meat Quality and Post-mortem Glycolysis Metabolism of Muscles with Different Fiber Types.

    Science.gov (United States)

    Wang, Xiaofei; Li, Jiaolong; Cong, Jiahui; Chen, Xiangxing; Zhu, Xudong; Zhang, Lin; Gao, Feng; Zhou, Guanghong

    2017-11-29

    Preslaughter transport has been reported to decrease the quality of breast meat but not thigh meat of broilers. However, tissue-specific difference in glycogen metabolism between breast and thigh muscles of transported broilers has not been well studied. We thus investigated the differences in meat quality, adenosine phosphates, glycolysis, and bound key enzymes associated with glycolysis metabolism in skeletal muscles with different fiber types of preslaughter transported broilers during summer. Compared to a 0.5 h transport, a 3 h transport during summer decreased ATP content, increased AMP content and AMP/ATP ratio, and accelerated glycolysis metabolism via the upregulation of glycogen phosphorylase expression accompanied by increased activities of bound glycolytic enzymes (hexokinase, pyruvate kinase, and lactate dehydrogenase) in pectoralis major muscle, which subsequently increased the likelihood of pale, soft, and exudative-like breast meat. On the other hand, a 3 h transport induced only a moderate glycolysis metabolism in tibialis anterior muscle, which did not cause any noticeable changes in the quality traits of the thigh meat.

  3. Resveratrol Inhibits ROS-Promoted Activation and Glycolysis of Pancreatic Stellate Cells via Suppression of miR-21

    Directory of Open Access Journals (Sweden)

    Bin Yan

    2018-01-01

    Full Text Available Activation of pancreatic stellate cells (PSCs initiates pancreatic fibrosis in chronic pancreatitis and furnishes a niche that enhances the malignancy of pancreatic cancer cells (PCCs in pancreatic ductal adenocarcinoma (PDAC. Resveratrol (RSV, a natural polyphenol, exhibits potent antioxidant and anticancer effects. However, whether and how RSV influences the biological properties of activated PSCs and the effects of these changes on tumor remain unknown. In the present study, we found that RSV impeded hydrogen peroxide-driven reactive oxygen species- (ROS- induced activation, invasion, migration, and glycolysis of PSCs. In addition, miR-21 expression in activated PSCs was downregulated after RSV treatment, whereas the PTEN protein level increased. miR-21 silencing attenuated ROS-induced activation, invasion, migration, and glycolysis of PSCs, whereas the overexpression of miR-21 rescued the responses of PSCs treated with RSV. Moreover, RSV or N-acetyl-L-cysteine (NAC administration or miR-21 knockdown in PSCs reduced the invasion and migration of PCCs in coculture, and the effects of RSV were partly reversed by miR-21 upregulation. Collectively, RSV inhibits PCC invasion and migration through suppression of ROS/miR-21-mediated activation and glycolysis in PSCs. Therefore, targeting miR-21-mediated glycolysis by RSV in tumor stroma may serve as a new strategy for clinical PDAC prevention or treatment.

  4. BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells.

    Science.gov (United States)

    An, Ming-Xin; Li, Si; Yao, Han-Bing; Li, Chao; Wang, Jia-Mei; Sun, Jia; Li, Xin-Yu; Meng, Xiao-Na; Wang, Hua-Qin

    2017-12-04

    Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents. © 2017 An et al.

  5. Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane.

    Science.gov (United States)

    Epstein, Tamir; Xu, Liping; Gillies, Robert J; Gatenby, Robert A

    2014-01-01

    Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal oxygen concentrations, also known as the Warburg effect. This metabolism is considered abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood. We examined changes in glucose metabolism following perturbations in membrane activity in different normal and tumor cell lines and found that inhibition or activation of pumps on the cell membrane led to reduction or increase in glycolysis, respectively, while oxidative phosphorylation remained unchanged. Computational simulations demonstrated that these findings are consistent with a new model of normal physiological cellular metabolism in which efficient mitochondrial oxidative phosphorylation supplies chronic energy demand primarily for macromolecule synthesis and glycolysis is necessary to supply rapid energy demands primarily to support membrane pumps. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. The predictions were confirmed experimentally. Our results show that glycolytic metabolism serves a critical physiological function under normoxic conditions by responding to rapid energetic demand, mainly from membrane transport activities, even in the presence of oxygen. This supports a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Cells use efficient but slow-responding aerobic metabolism

  6. Inhibition of Non-flux-Controlling Enzymes Deters Cancer Glycolysis by Accumulation of Regulatory Metabolites of Controlling Steps.

    Science.gov (United States)

    Marín-Hernández, Álvaro; Rodríguez-Zavala, José S; Del Mazo-Monsalvo, Isis; Rodríguez-Enríquez, Sara; Moreno-Sánchez, Rafael; Saavedra, Emma

    2016-01-01

    Glycolysis provides precursors for the synthesis of macromolecules and may contribute to the ATP supply required for the constant and accelerated cellular duplication in cancer cells. In consequence, inhibition of glycolysis has been reiteratively considered as an anti-cancer therapeutic option. In previous studies, kinetic modeling of glycolysis in cancer cells allowed the identification of the main steps that control the glycolytic flux: glucose transporter, hexokinase (HK), hexose phosphate isomerase (HPI), and glycogen degradation in human cervix HeLa cancer cells and rat AS-30D ascites hepatocarcinoma. It was also previously experimentally determined that simultaneous inhibition of the non-controlling enzymes lactate dehydrogenase (LDH), pyruvate kinase (PYK), and enolase (ENO) brings about significant decrease in the glycolytic flux of cancer cells and accumulation of intermediate metabolites, mainly fructose-1,6-bisphosphate (Fru1,6BP), and dihydroxyacetone phosphate (DHAP), which are inhibitors of HK and HPI, respectively. Here it was found by kinetic modeling that inhibition of cancer glycolysis can be attained by blocking downstream non flux-controlling steps as long as Fru1,6BP and DHAP, regulatory metabolites of flux-controlling enzymes, are accumulated. Furthermore, experimental results and further modeling showed that oxamate and iodoacetate inhibitions of PYK, ENO, and glyceraldehyde3-phosphate dehydrogenase (GAPDH), but not of LDH and phosphoglycerate kinase, induced accumulation of Fru1,6BP and DHAP in AS-30D hepatoma cells. Indeed, PYK, ENO, and GAPDH exerted the highest control on the Fru1,6BP and DHAP concentrations. The high levels of these metabolites inhibited HK and HPI and led to glycolytic flux inhibition, ATP diminution, and accumulation of toxic methylglyoxal. Hence, the anticancer effects of downstream glycolytic inhibitors are very likely mediated by this mechanism. In parallel, it was also found that uncompetitive inhibition of the

  7. Intraosseous osteolytic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Adler, C.P.; Wenz, W.

    1981-10-01

    Any pathological damage occurring in a bone will produce either an osteolytic or osteosclerotic lesion which can be seen in the macroscopic specimen as well as in the roentgenogram. Various bone lesions may lead to local destructions of the bone. An osteoma or osteoplastic osteosarcoma produces an osteosclerotic lesion showing a dense mass in the roentgenogram; a chondroblastoma or an osteoclastoma, on the other hand, induces an osteolytic focal lesion. This paper presents examples of different osteolytic lesions of the humerus. An osteolytic lesion seen in the roentgenogram may be either produced by an underlying non-ossifying fibroma of the bone, by fibrous dysplasia, osteomyelitis or Ewing's sarcoma. Differential diagnostic considerations based on the radiological picture include eosinophilic bone granuloma, juvenile or aneurysmal bone cyst, multiple myeloma or bone metastases. Serious differential diagnostic problems may be involved in case of osteolytic lesions occurring in the humerus. Cases of this type involving complications have been reported and include the presence of an teleangiectatic osteosarcoma as well as that of a hemangiosarcoma of the bone.

  8. Total algorithms

    NARCIS (Netherlands)

    Tel, G.

    We define the notion of total algorithms for networks of processes. A total algorithm enforces that a "decision" is taken by a subset of the processes, and that participation of all processes is required to reach this decision. Total algorithms are an important building block in the design of

  9. Diffuse cavitary lung lesions

    Energy Technology Data Exchange (ETDEWEB)

    Grunzke, Mindy; Garrington, Timothy [University of Colorado Denver, Department of Pediatrics, Aurora, CO (United States); The Children' s Hospital, Rick Wilson Center for Cancer and Blood Disorders, Aurora, CO (United States); Hayes, Kari [The Children' s Hospital, Pediatric Radiology, Aurora, CO (United States); Bourland, Wendy [Children' s Hospital at St. Francis, Warren Clinic, Inc., Tulsa, OK (United States)

    2010-02-15

    An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for {sup 18}F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

  10. Diffuse cavitary lung lesions

    International Nuclear Information System (INIS)

    Grunzke, Mindy; Garrington, Timothy; Hayes, Kari; Bourland, Wendy

    2010-01-01

    An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for 18 F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

  11. Uterine Vascular Lesions

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  12. Male breast lesions

    International Nuclear Information System (INIS)

    Matushita, J.P.K.; Andrade, L.G. de; Carregal, E.; Marimatsu, R.I.; Matushita, J.S.

    1989-01-01

    Roentgenographic examination of the male breast is an important aspect of the continued, intensive investigation of the radiologic morphology of the normal and diseased breast conducted in 17 cases examined at the Instituto Nacional do Cancer - RJ. It is purpose of this report to present the Roentgen appearance of various lesions of the male breast as they have been found in our practice and also to stress some of the difficulties in the differential diagnosis of these lesions. (author) [pt

  13. NEOPLASTIC LESIONS OF THE APPENDIX

    Directory of Open Access Journals (Sweden)

    Piotr Bryk

    2013-11-01

    Full Text Available The aim of the research was to present the clinical observations of neoplastic lesions of the appendix (one carcinoid and two mucous cysts and to discuss various manners of treatment and prognosis. Material and methods: The authors of the following paper present a description of three cases of appendix tumours, two patients with a mucous cyst and a patient with carcinoid, against the background of all the appendectomies performed at the Clinical Department of General, Endocrine and Oncological Surgery of the Provincial Polyclinical Hospital in Kielce in the years 2005–2011. Results : Within the 7-year period, a total of 11 719 surgical operations have been performed, where 834 (7.1% were that of appendectomy. Among all of the removed vermiform appendixes, neoplastic lesions occurred in three cases constituting a mere 0.3% of all of the appendectomies performed within that period. In two of the cases there was a suspicion of mucous cysts before the surgical operation. In none of the above-mentioned cases was is possible to ultimately establish the diagnosis before the operation. The patients were subjected to a simple appendectomy. The patients are in good clinical health, with no signs of relapse. Conclusions : The presented cases of patients with appendix tumours illustrate the difficulty of preoperative detection of a neoplastic lesion. This is mainly due to a scantily symptomatic course or symptoms typical of appendicitis. In light of this, histopathological examination of each appendix should be treated as obligatory.

  14. How much we know about bisphosphonate lesions

    Directory of Open Access Journals (Sweden)

    Pešić Zoran

    2016-01-01

    Full Text Available Introduction: Bisphosphonate drugs are used in the treatment of the osteoporosis and malignant processes in the bone tissue. As a result of this use bisphosphonate lesions are formed in bone tissue and oral mucosis, which representing a remarkable therapeutic problem. The aim of this study was to determine how many dentists in general practice are familiar with the character, diagnosis and therapy bisphosphonate lesions. Material and Methods: An anonymous questionnaire of 13 questions was conducted in dental practices in Nis County in the period from October 2015 to December 2015. The obtained data were statistically analyzed. Results: A total of 60% dentists knew what drugs are used in the treatment of osteoporosis and malignant processes in the bones. 25% knew what the bisphosphonate bone lesions are . 66, 6% of dentists knewn what is the prevention of bisphosphonate lesions. 63.3% of dentists are aware of the complications bisphosphonate lesions. Conclusion: Dentists in general practices are insufficiently familiar with the character, diagnosis and treatment of bisphosphonate lesions. We should activate all entities that participate in more continuous medical education, in order to achieve a higher level of prevention of these therapeutic ungrateful lesions.

  15. Benign fibroosseous lesions

    Directory of Open Access Journals (Sweden)

    Cansu Köseoğlu Seçgin

    2016-05-01

    Full Text Available Benign fibroosseous lesions represent a group of lesions that share the same basic evolutive mechanism and are characterized by replacement of normal bone with a fibrous connective tissue that gradually undergoes mineralization. These lesions are presented by a variety of diseases including developmental, reactive-dysplastic processes and neoplasms. Depending on the nature and amount of calcified tissue, they can be observed as radiolucent, mixed or radiopaque. Their radiographic features could be well-defined or indistinguishable from the surrounding bone tissue. They can be asymptomatic as in osseous dysplasias and can be detected incidentally on radiographs, or they can lead to expansion in the affected bone as in ossifying fibroma. All fibroosseous lesions seen in the jaws and face are variations of the same histological pattern. Therefore, detailed clinical and radiographic evaluation in differential diagnosis is important. In this review, fibroosseous benign lesions are classified as osseous dysplasia, fibrous dysplasia and fibroosseous tumors; and radiographic features and differential diagnosis of these lesions are reviewed taking into account this classification.

  16. Totally James

    Science.gov (United States)

    Owens, Tom

    2006-01-01

    This article presents an interview with James Howe, author of "The Misfits" and "Totally Joe". In this interview, Howe discusses tolerance, diversity and the parallels between his own life and his literature. Howe's four books in addition to "The Misfits" and "Totally Joe" and his list of recommended books with lesbian, gay, bisexual, transgender,…

  17. 3-bromopyruvate inhibits glycolysis, depletes cellular glutathione, and compromises the viability of cultured primary rat astrocytes.

    Science.gov (United States)

    Ehrke, Eric; Arend, Christian; Dringen, Ralf

    2015-07-01

    The pyruvate analogue 3-bromopyruvate (3-BP) is an electrophilic alkylator that is considered a promising anticancer drug because it has been shown to kill cancer cells efficiently while having little toxic effect on nontumor cells. To test for potential adverse effects of 3-BP on brain cells, we exposed cultured primary rat astrocytes to 3-BP and investigated the effects of this compound on cell viability, glucose metabolism, and glutathione (GSH) content. The presence of 3-BP severely compromised cell viability and slowed cellular glucose consumption and lactate production in a time- and concentration-dependent manner, with half-maximal effects observed at about 100 µM 3-BP after 4 hr of incubation. The cellular hexokinase activity was not affected in 3-BP-treated astrocytes, whereas within 30 min after application of 3-BP the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was inhibited, and cellular GSH content was depleted in a concentration-dependent manner, with half-maximal effects observed at about 30 µM 3-BP. The depletion of cellular GSH after exposure to 100 µM 3-BP was not prevented by the presence of 10 mM of the monocarboxylates lactate or pyruvate, suggesting that 3-BP is not taken up into astrocytes predominantly by monocarboxylate transporters. The data suggest that inhibition of glycolysis by inactivation of GAPDH and GSH depletion contributes to the toxicity that was observed for 3-BP-treated cultured astrocytes. © 2014 Wiley Periodicals, Inc.

  18. Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease

    Science.gov (United States)

    Koppe, Laetitia; Nyam, Elsa; Vivot, Kevin; Manning Fox, Jocelyn E.; Dai, Xiao-Qing; Nguyen, Bich N.; Attané, Camille; Moullé, Valentine S.; MacDonald, Patrick E.; Ghislain, Julien

    2016-01-01

    Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis. PMID:27525435

  19. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  20. ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD+ Depletion

    Directory of Open Access Journals (Sweden)

    Elise Fouquerel

    2014-09-01

    Full Text Available ARTD1 (PARP1 is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose (PAR in response to strand breaks, and it plays an important role in cell death following excessive DNA damage. ARTD1-induced cell death is associated with NAD+ depletion and ATP loss; however, the molecular mechanism of ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared the effects of ARTD1 activation and direct NAD+ depletion. We found that ARTD1-mediated PAR synthesis, but not direct NAD+ depletion, resulted in a block to glycolysis and ATP loss. We then established a proteomics-based PAR interactome after DNA damage and identified hexokinase 1 (HK1 as a PAR binding protein. HK1 activity is suppressed following nuclear ARTD1 activation and binding by PAR. These findings help explain how prolonged activation of ARTD1 triggers energy collapse and cell death, revealing insight into the importance of nucleus-to-mitochondria communication via ARTD1 activation.

  1. Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis.

    Science.gov (United States)

    Ruprecht, Benjamin; Zaal, Esther A; Zecha, Jana; Wu, Wei; Berkers, Celia R; Kuster, Bernhard; Lemeer, Simone

    2017-04-15

    HER2/ERBB2-overexpressing breast cancers targeted effectively by the small-molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In this study, we employed explorative mass spectrometry to profile proteome, kinome, and phosphoproteome changes in an established model of lapatinib resistance to systematically investigate initial inhibitor response and subsequent reprogramming in resistance. The resulting dataset, which collectively contains quantitative data for >7,800 proteins, >300 protein kinases, and >15,000 phosphopeptides, enabled deep insight into signaling recovery and molecular reprogramming upon resistance. Our data-driven approach confirmed previously described mechanisms of resistance (e.g., AXL overexpression and PIK3 reactivation), revealed novel pharmacologically actionable targets, and confirmed the expectation of significant heterogeneity in molecular resistance drivers inducing distinct phenotypic changes. Furthermore, our approach identified an extensive and exclusively phosphorylation-mediated reprogramming of glycolytic activity, supported additionally by widespread changes of corresponding metabolites and an increased sensitivity towards glycolysis inhibition. Collectively, our multi-omic analysis offers deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. Cancer Res; 77(8); 1842-53. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. An engineered non-oxidative glycolysis pathway for acetone production in Escherichia coli.

    Science.gov (United States)

    Yang, Xiaoyan; Yuan, Qianqian; Zheng, Yangyang; Ma, Hongwu; Chen, Tao; Zhao, Xueming

    2016-08-01

    To find new metabolic engineering strategies to improve the yield of acetone in Escherichia coli. Results of flux balance analysis from a modified Escherichia coli genome-scale metabolic network suggested that the introduction of a non-oxidative glycolysis (NOG) pathway would improve the theoretical acetone yield from 1 to 1.5 mol acetone/mol glucose. By inserting the fxpk gene encoding phosphoketolase from Bifidobacterium adolescentis into the genome, we constructed a NOG pathway in E.coli. The resulting strain produced 47 mM acetone from glucose under aerobic conditions in shake-flasks. The yield of acetone was improved from 0.38 to 0.47 mol acetone/mol glucose which is a significant over the parent strain. Guided by computational analysis of metabolic networks, we introduced a NOG pathway into E. coli and increased the yield of acetone, which demonstrates the importance of modeling analysis for the novel metabolic engineering strategies.

  3. Longevity of U cells of differentiated yeast colonies grown on respiratory medium depends on active glycolysis.

    Science.gov (United States)

    Čáp, Michal; Váchová, Libuše; Palková, Zdena

    2015-01-01

    Colonies of Saccharomyces cerevisiae laboratory strains pass through specific developmental phases when growing on solid respiratory medium. During entry into the so-called alkali phase, in which ammonia signaling is initiated, 2 prominent cell types are formed within the colonies: U cells in upper colony regions, which have a longevity phenotype and activate the expression of a large number of metabolic genes, and L cells in lower regions, which die more quickly and exhibit a starvation phenotype. Here, we performed a detailed analysis of the activities of enzymes of central carbon metabolism in lysates of both cell types and determined several fermentation end products, showing that previously reported expression differences are reflected in the different enzymatic capabilities of each cell type. Hence, U cells, despite being grown on respiratory medium, behave as fermenting cells, whereas L cells rely on respiratory metabolism and possess active gluconeogenesis. Using a spectrum of different inhibitors, we showed that glycolysis is essential for the formation, and particularly, the survival of U cells. We also showed that β-1,3-glucans that are released from the cell walls of L cells are the most likely source of carbohydrates for U cells.

  4. Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing Glycolysis and Glucose Oxidation Homeostasis

    Directory of Open Access Journals (Sweden)

    Jie Tao

    2018-03-01

    Full Text Available The goal of this investigation was to define the molecular mechanism underlying physiologic conversion of immune tolerance to resolution of the acute inflammatory response, which is unknown. An example of this knowledge gap and its clinical importance is the broad-based energy deficit and immunometabolic paralysis in blood monocytes from non-survivors of human and mouse sepsis that precludes sepsis resolution. This immunometabolic dysregulation is biomarked by ex vivo endotoxin tolerance to increased glycolysis and TNF-α expression. To investigate how tolerance switches to resolution, we adapted our previously documented models associated with acute inflammatory, immune, and metabolic reprogramming that induces endotoxin tolerance as a model of sepsis in human monocytes. We report here that mitochondrial sirtuin 4 (SIRT4 physiologically breaks tolerance and resolves acute inflammation in human monocytes by coordinately reprogramming of metabolism and bioenergetics. We find that increased SIRT4 mRNA and protein expression during immune tolerance counters the increase in pyruvate dehydrogenase kinase 1 (PDK1 and SIRT1 that promote tolerance by switching glucose-dependent support of immune resistance to fatty acid oxidation support of immune tolerance. By decreasing PDK1, pyruvate dehydrogenase complex reactivation rebalances mitochondrial respiration, and by decreasing SIRT1, SIRT4 represses fatty acid oxidation. The precise mechanism for the mitochondrial SIRT4 nuclear feedback is unclear. Our findings are consistent with a new concept in which mitochondrial SIRT4 directs the axis that controls anabolic and catabolic energy sources.

  5. Global ablation of the mitochondrial calcium uniporter increases glycolysis in cortical neurons subjected to energetic stressors.

    Science.gov (United States)

    Nichols, Matthew; Elustondo, Pia A; Warford, Jordan; Thirumaran, Aruloli; Pavlov, Evgeny V; Robertson, George S

    2017-08-01

    The effects of global mitochondrial calcium (Ca 2+ ) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca 2+ handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca 2+ uptake and Ca 2+ -induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage. Energetic stress enhanced glycolysis and depressed Complex I activity in global MCU null, relative to WT, cortical neurons. HI reduced forebrain NADH levels more in global MCU nulls than WT mice suggesting that increased glycolytic consumption of NADH suppressed Complex I activity. Compared to WT neurons, pyruvate dehydrogenase (PDH) was hyper-phosphorylated in MCU nulls at several sites that lower the supply of substrates for the tricarboxylic acid cycle. Elevation of cytosolic Ca 2+ with glutamate or ionomycin decreased PDH phosphorylation in MCU null neurons suggesting the use of alternative mitochondrial Ca 2+ transport. Under basal conditions, global MCU nulls showed similar increases of Ca 2+ handling genes in the hippocampus as WT mice subjected to HPC. We propose that long-term adaptations, common to HPC, in global MCU nulls compromise resistance to HI brain injury and disrupt HPC.

  6. Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

    Directory of Open Access Journals (Sweden)

    Hamed Mortazavi

    2017-01-01

    Full Text Available Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated and rough (squamous epithelium-originated. Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic, and mesenchymal lesions (benign and malignant neoplasms. In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.

  7. Taurine up-regulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Yang-Hsiang; Wu, Meng-Han; Huang, Ya-Hui; Yeh, Chau-Ting; Cheng, Mei-Ling; Chi, Hsiang-Cheng; Tsai, Chung-Ying; Chung, I-Hsiao; Chen, Ching-Ying; Lin, Kwang-Huei

    2018-01-01

    Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of taurine up-regulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion, and glycolysis through suppression of microRNA (miR)-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3' untranslated region of adenosine monophosphate-activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR-455-3p/AMPKβ2 axis regulates cell growth, metastasis, and glycolysis through regulation of hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel regulatory associations among TUG1, miR-455-3p, AMPKβ2, and HK2 are an important determinant of glycolytic metabolism and metastasis in HCC cells and support the potential utility of targeting TUG1/HK2 as a therapeutic strategy for HCC. (Hepatology 2018;67:188-203). © 2017 by the American Association for the Study of Liver Diseases.

  8. Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis.

    Science.gov (United States)

    Clara, Rosmarie; Langhans, Wolfgang; Mansouri, Abdelhak

    2016-03-01

    Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect. First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer. OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA-induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it. These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. A shift to glycolysis accompanies the inflammatory changes in PBMCs from individuals with an IQ-discrepant memory.

    Science.gov (United States)

    Wolfe, Hannah; Hannigan, Caoimhe; O'Sullivan, Michael; Carroll, Liam Barry; Brennan, Sabina; Lawlor, Brian; Robertson, Ian H; Lynch, Marina

    2018-04-15

    Identification of a blood-based biomarker that can detect early cognitive decline presents a significant healthcare challenge. We prepared peripheral blood mononuclear cells (PBMCs) from individuals who had a poorer than predicted performance in their delayed recall performance on the Logical Memory II Subtest of the Wechsler Memory Scale (WMS) relative to their IQ estimated by the National Adult Reading Test (NART); we described these individuals as IQ-discrepant, compared with IQ-consistent, individuals. Stimulation with Aβ + LPS increased production of TNFα to a greater extent in cells from IQ-discrepant, compared with IQ-consistent, individuals. This was associated with a shift towards glycolysis and the evidence indicates that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3 plays a role in driving glycolysis. A similar shift towards glycolysis was observed in MDMs prepared from IQ-discrepant, compared with IQ-consistent, individuals. The important finding here is that we have established an increased sensitivity to Aβ + LPS stimulation in PBMCs from individuals that under-perform on a memory task, relative to their estimated premorbid IQ, which may be an indicator of early cognitive decline. This may be a useful tool in determining the presence of early cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. The Variations of Glycolysis and TCA Cycle Intermediate Levels Grown in Iron and Copper Mediums of Trichoderma harzianum.

    Science.gov (United States)

    Tavsan, Zehra; Ayar Kayali, Hulya

    2015-05-01

    The efficiency of optimal metabolic function by microorganism depends on various parameters, especially essential metal supplementation. In the present study, the effects of iron and copper metals on metabolism were investigated by determination of glycolysis and tricarboxylic acid (TCA) cycle metabolites' levels with respect to the metal concentrations and incubation period in Trichoderma harzianum. The pyruvate and citrate levels of T. harzianum increased up to 15 mg/L of copper via redirection of carbon flux though glycolysis by suppression of pentose phosphate pathway (PPP). However, the α-ketoglutarate levels decreased at concentration higher than 5 mg/L of copper to overcome damage of oxidative stress. The fumarate levels correlated with the α-ketoglutarate levels because of substrate limitation. Besides, in T. harzianum cells grown in various concentrations of iron-containing medium, the intracellular pyruvate, citrate, and α-ketoglutarate levels showed positive correlation with iron concentration due to modifying of expression of glycolysis and TCA cycle enzymes via a mechanism involving cofactor or allosteric regulation. However, as a result of consuming of prior substrates required for fumarate production, its levels rose up to 10 mg/L.

  11. Use of Molecular Imaging Markers of Glycolysis, Hypoxia and Proliferation (18F-FDG, 64Cu-ATSM and 18F-FLT) in a Dog with Fibrosarcoma

    DEFF Research Database (Denmark)

    Zornhagen, Kamilla; Clausen, Malene; Hansen, Anders Elias

    2015-01-01

    Glycolysis, hypoxia, and proliferation are important factors in the tumor microenvironment contributing to treatment-resistant aggressiveness. Imaging these factors using combined functional positron emission tomography and computed tomography can potentially guide diagnosis and management...

  12. Cellular targets of the myeloperoxidase-derived oxidant hypothiocyanous acid (HOSCN) and its role in the inhibition of glycolysis in macrophages

    DEFF Research Database (Denmark)

    Love, D; Barrett, T.J.; White, M.Y.

    2016-01-01

    the cellular targets of HOSCN in macrophages (J774A.1). We report that multiple thiol-containing proteins involved in metabolism and glycolysis; fructose bisphosphate aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and creatine kinase, together with a number of chaperone......, antioxidant and structural proteins, were modified in a reversible manner in macrophages treated with HOSCN. The modification of the metabolic enzymes was associated with a decrease in basal glycolysis, glycolytic reserve, glycolytic capacity and lactate release, which was only partly reversible on further...... incubation in the absence of HOSCN. Inhibition of glycolysis preceded cell death and was seen in cells exposed to low concentrations (r25 mM) of HOSCN. The ability of HOSCN to inhibit glycolysis and perturb energy production is likely to contribute to the cell death seen in macrophages on further incubation...

  13. Precancerous Skin Lesions.

    Science.gov (United States)

    Ferrándiz, C; Malvehy, J; Guillén, C; Ferrándiz-Pulido, C; Fernández-Figueras, M

    Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Common conjunctival lesions

    African Journals Online (AJOL)

    Conjunctival lesions are frequently seen in the eye clinic, because the conjunctiva is readily ... anti-histamine drops and mast cell stabilisers can be used. e more severe cases have to be .... Ehlers J, Shah C . The Wills Eye Manual. Office and.

  15. Skin lesion removal

    Science.gov (United States)

    ... likely to be done when there is a concern about a skin cancer. Most often, an area the shape of an ellipse is removed, as this makes it easier to close with stitches. The entire lesion is removed, going as deep as the fat, if needed, to ...

  16. Genital lesions following bestiality

    Directory of Open Access Journals (Sweden)

    Mittal A

    2000-01-01

    Full Text Available A 48-year-old man presented with painful genital lesions with history of bestiality and abnor-mal sexual behaviour. Examination revealed multiple irregular tender ulcers and erosions, with phimosis and left sided tender inguinal adenopathy. VDRL, TPHA, HIV-ELISA were negative. He was treated with ciprofloxacin 500mg b.d. along with saline compresses with complete resolution.

  17. Cellular Glycolysis and The Differential Survival of Lung Fibroblast and Lung Carcinoma Cell Lines.

    Science.gov (United States)

    Farah, Ibrahim O

    2016-04-01

    Tumor growth and abnormal cell survival were shown to be associated with a number of cellular metabolic abnormalities revealed by impaired oral glucose tolerance, depressed lipoprotein lipase activity leading to hypertriglyceridemia, and changes in amino acid profile as evidenced by increased plasma free tryptophan levels in patients with breast, lung, colon, stomach, and other cancers from various origins. The above findings seem to relate to or indicate a shift to non-oxidative metabolic pathways in cancer. In contrast to normal cells, cancer cells may lose the ability to utilize aerobic respiration due to either defective mitochondria or hypoxia within the tumor microenvironments. Glucose was shown to be the major energy source in cancer cells where it utilizes aerobic /anaerobic glycolysis with the resultant lactic acid formation. The role of energetic modulations and use of glycolytic inhibitors on cancer/normal cell survival is not clearly established in the literature. We hypothesize that natural intermediates of glycolysis and the citric acid cycle will differentially and negatively impact the cancer phenotype in contrast to their no effects on the normal cell phenotype. Therefore, the purpose of this study was to evaluate six potential glycolytic modulators namely, Pyruvic acid, oxalic acid, Zn acetate, sodium citrate, fructose diphosphate (FDP) and sodium bicarbonate at μM concentrations on growing A549 (lung cancer) and MRC-5 (normal; human lung fibroblast) cell lines with the objective of determining their influence on visual impact, cell metabolic activity, cell viability and end-point cell survival. Exposed and non-exposed cells were tested with phase-contrast micro-scanning, survival/death and metabolic activity trends through MTT-assays, as well as death end-point determinations by testing re-growth on complete media and T4 cellometer counts. Results showed that oxalic acid and Zn acetate both influenced the pH of the medium and resulted in

  18. Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

    International Nuclear Information System (INIS)

    Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng; Fu, Chao; Cao, Zhang

    2015-01-01

    Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser 461 , along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2

  19. Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Fu, Chao [Department of Ultrasonography, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Cao, Zhang, E-mail: zzzhangcao@126.com [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China)

    2015-08-28

    Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser{sup 461}, along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2.

  20. Regulatory properties of 6-phosphofructokinase and control of glycolysis in boar spermatozoa.

    Science.gov (United States)

    Kamp, G; Schmidt, H; Stypa, H; Feiden, S; Mahling, C; Wegener, G

    2007-01-01

    Glycolysis is crucial for sperm functions (motility and fertilization), but how this pathway is regulated in spermatozoa is not clear. This prompted to study the location and the regulatory properties of 6-phosphofructokinase (PFK, EC 2.7.1.11), the most important element for control of glycolytic flux. Unlike some other glycolytic enzymes, PFK showed no tight binding to sperm structures. It could readily be extracted from ejaculated boar spermatozoa by sonication and was then chromatographically purified. At physiological pH, the enzyme was allosterically inhibited by near-physiological concentrations of its co-substrate ATP, which induced co-operativity, i.e. reduced the affinity for the substrate fructose 6-phosphate. Inhibition by ATP was reinforced by citrate and H+. Above pH 8, PFK lost all its regulatory properties and showed maximum activity. However, in the physiological pH range, PFK activity was very sensitive to small changes in effectors. At near-physiological substrate concentrations, PFK activity requires activators (de-inhibitors) of which the combination of AMP and fructose 2,6-bisphosphate (F2,6P2) was most efficient as a result of synergistic effects. The kinetics of PFK suggest AMP, F2,6P2, H+, and citrate as allosteric effectors controlling PFK activity in boar spermatozoa. Using immunogold labeling, PFK was localized in the mid-piece and principal piece of the flagellum as well as in the acrosomal area at the top of the head and in the cytoplasmic droplets released from the mid-piece after ejaculation.

  1. Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.

    Science.gov (United States)

    Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L Felipe; Inestrosa, Nibaldo C

    2016-12-09

    The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases.

    Science.gov (United States)

    Rueda, Elda M; Johnson, Jerry E; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J; Sigel, Irena; Chaney, Shawnta Y; Fox, Donald A

    2016-01-01

    The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. Our goals were twofold: 1) to characterize the gene expression, protein expression, and activity of key synthesizing and regulating enzymes of energy metabolism in the whole mouse retina, retinal compartments, and/or cells and 2) to provide an integrative analysis of the results related to function. mRNA expression data of energy-related genes were extracted from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal microscopy, and enzymatic histochemistry. The immunoreactivity levels of well-characterized antibodies, for all major retinal cells and their compartments, were obtained using our established semiquantitative confocal and imaging techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH) activity was determined histochemically. The Affymetrix data revealed varied gene expression patterns of the ATP synthesizing and regulating enzymes found in the muscle, liver, and brain. Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity of the antibodies and of the COX and LDH activity showed the high capacity of photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with pyruvate revealed that LDH-5 was localized in the photoreceptor inner segments. The

  3. Morel-Lavallee lesion.

    Science.gov (United States)

    Li, Hui; Zhang, Fangjie; Lei, Guanghua

    2014-01-01

    To review current knowledge of the Morel-Lavallee lesion (MLL) to help clinicians become familiar with this entity. Familiarization may decrease missed diagnoses and misdiagnoses. It could also help steer the clinician to the proper treatment choice. A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords: Morel-Lavallee lesion, closed degloving injury, concealed degloving injury, Morel-Lavallee effusion, Morel-Lavallee hematoma, posttraumatic pseudocyst, posttraumatic soft tissue cyst. Chinese and English language literatures relevant to the subject were collected. Their references were also reviewed. Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury. It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia. Apart from the classic location over the region of the greater trochanter, MLLs have been described in other parts of the body. The natural history of MLL has not yet been established. The lesion may decrease in volume, remain stable, enlarge progressively or show a recurrent pattern. Diagnosis of MLL was often missed or delayed. Ultrasonography, computed tomography, and magnetic resonance imaging have great value in the diagnosis of MLL. Treatment of MLL has included compression, local aspiration, open debridement, and sclerodesis. No standard treatment has been established. A diagnosis of MLL should be suspected when a soft, fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury. Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis. Treatment decisions should base on association with fractures, the condition of the lesion, symptom and desire of the patient.

  4. Maxillomandibular giant osteosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Constantino LEDESMA-MONTES

    2018-06-01

    Full Text Available Abstract Giant Osteosclerotic Lesions (GOLs are a group of rarely reported intraosseous lesions. Their precise diagnosis is important since they can be confused with malignant neoplasms. Objective This retrospective study aimed to record and analyze the clinical and radiographic Giant Osteosclerotic Lesions (GOLs detected in the maxillomandibular area of patients attending to our institution. Materials and Methods: Informed consent from the patients was obtained and those cases of 2.5 cm or larger lesions with radiopaque or mixed (radiolucid-radiopaque appearance located in the maxillofacial bones were selected. Assessed parameters were: age, gender, radiographic aspect, shape, borders, size, location and relations to roots. Lesions were classified as radicular, apical, interradicular, interradicular-apical, radicular-apical or located in a previous teeth extraction area. Additionally, several osseous and dental developmental alterations (DDAs were assessed. Results Seventeen radiopacities in 14 patients were found and were located almost exclusively in mandible and were two types: idiopathic osteosclerosis and condensing osteitis. GOLs were more frequent in females, and in the anterior and premolar zones. 94.2% of GOLs were qualified as idiopathic osteosclerosis and one case was condensing osteitis. All studied cases showed different osseous and dental developmental alterations (DDAs. The most common were: Microdontia, hypodontia, pulp stones, macrodontia and variations in the mental foramina. Conclusions GOLs must be differentiated from other radiopaque benign and malignant tumors. Condensing osteitis, was considered an anomalous osseous response induced by a chronic low-grade inflammatory stimulus. For development of idiopathic osteosclerosis, two possible mechanisms could be related. The first is modification of the normal turnover with excessive osseous deposition. The second mechanism will prevent the normal bone resorption, arresting the

  5. Lacrimal gland lesions in Denmark between 1974 and 2007

    DEFF Research Database (Denmark)

    von Holstein, Sarah Linéa; Therkildsen, Marianne Hamilton; Prause, Jan Ulrik

    2013-01-01

    -2007 were identified by searching two population-based registries. Specimens were collected and re-evaluated. The following data were collected: age, gender, indications for surgical intervention and local recurrence. Results: A total of 232 lesions from 210 patients with a histologically verified lesion...

  6. Lesion progression in post-treatment persistent endodontic lesions.

    Science.gov (United States)

    Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

    2012-10-01

    Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. SDHB downregulation facilitates the proliferation and invasion of colorectal cancer through AMPK functions excluding those involved in the modulation of aerobic glycolysis.

    Science.gov (United States)

    Xiao, Zhiming; Liu, Shaojun; Ai, Feiyan; Chen, Xiong; Li, Xiayu; Liu, Rui; Ren, Weiguo; Zhang, Xuemei; Shu, Peng; Zhang, Decai

    2018-01-01

    Loss-of-function of succinate dehydrogenase-B (SDHB) is a predisposing factor of aerobic glycolysis and cancer progression. Adenosine monophosphate activated protein kinase (AMPK) is involved in the regulation of aerobic glycolysis and the diverse hallmarks of cancer. The present study investigated whether AMPK mediated the regulatory effects of SDHB in aerobic glycolysis and cancer growth. The expression of SDHB and AMPK in colorectal cancer (CRC) and normal tissues was assessed by western blotting. HT-29 CRC cells were used to establish in vitro models of ectopic overexpression and knockdown of SDHB. SDHB was downregulated, while AMPK and phosphorylated-AMPK (Thr172) were upregulated in CRC tissues. Experiments involving the loss- or gain-of-function of SDHB, revealed that this protein negatively regulated AMPK by influencing its expression and activity. However, SDHB and AMPK were identified to suppress lactic acid production in CRC cells, indicating that each had an inhibitory effect on aerobic glycolysis. Therefore, the regulation of aerobic glycolysis by SDHB is unlikely to be mediated via AMPK. SDHB knockdown promoted the viability, migration and invasion of HT-29 cells, whereas inhibition of AMPK demonstrated the opposite effect. SDHB overexpression impaired cell migration and invasion, and this effect was reversed following AMPK activation. These results indicate that AMPK may mediate the effects of SDHB in CRC cell proliferation and migration. In conclusion, SDHB downregulation in CRC cells may increase AMPK activity, which may subsequently facilitate the proliferation and invasion of these cancer cells. However, the regulation of aerobic glycolysis by SDHB may be independent of AMPK. Further studies are warranted to elucidate the mechanism by which SDHB regulates aerobic glycolysis.

  8. Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage.

    Directory of Open Access Journals (Sweden)

    Atsushi Yamashita

    Full Text Available AIMS: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. METHODS: Macrophage-rich or smooth muscle cell (SMC-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS and interferon-γ (INFγ were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using (18F-fluorodeoxyglucose ((18F-FDG and pimonidazole, a marker of hypoxia. RESULTS: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20. The uptake of (18F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001. Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8 and pentose phosphate pathway (4 of 6 metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely

  9. Acute periodontal lesions.

    Science.gov (United States)

    Herrera, David; Alonso, Bettina; de Arriba, Lorenzo; Santa Cruz, Isabel; Serrano, Cristina; Sanz, Mariano

    2014-06-01

    This review provides updates on acute conditions affecting the periodontal tissues, including abscesses in the periodontium, necrotizing periodontal diseases and other acute conditions that cause gingival lesions with acute presentation, such as infectious processes not associated with oral bacterial biofilms, mucocutaneous disorders and traumatic and allergic lesions. A periodontal abscess is clinically important because it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth and bacteria within the abscess can spread and cause infections in other body sites. Different types of abscesses have been identified, mainly classified by their etiology, and there are clear differences between those affecting a pre-existing periodontal pocket and those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, while an evaluation of the need for systemic antimicrobial therapy will be made for each case, based on local and systemic factors. The definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal diseases present three typical clinical features: papilla necrosis, gingival bleeding and pain. Although the prevalence of these diseases is not high, their importance is clear because they represent the most severe conditions associated with the dental biofilm, with very rapid tissue destruction. In addition to bacteria, the etiology of necrotizing periodontal disease includes numerous factors that alter the host response and predispose to these diseases, namely HIV infection, malnutrition, stress or tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in nonresponding conditions, being the first option metronidazole. Once the acute

  10. Human papillomavirus in oral lesions Virus papiloma humano en lesiones orales

    Directory of Open Access Journals (Sweden)

    Joaquín V. Gónzalez

    2007-08-01

    Full Text Available Growing evidence suggests a role for human papillomavirus (HPV in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases; the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.Crecientes evidencias sugieren que el virus Papiloma humano (HPV tiene un rol en el cáncer oral; sin embargo su participación es todavía controvertida. Este estudio evalúa la frecuencia de ADN de HPV en una variedad de lesiones orales de pacientes de Argentina. Se seleccionaron 77 muestras de tejido oral de 66 pacientes (casos; el diagnóstico histo-patológico correspondió a: 11 lesiones benignas asociadas a HPV, 8 lesiones benignas no asociadas a HPV, 33 lesiones premalignas y 25 cánceres. Como controles se usaron 60 muestras de células exfoliadas de mucosa oral normal. La

  11. Localization of lesions in aphasia

    International Nuclear Information System (INIS)

    Hojo, Kei; Watanabe, Shunzo; Tasaki, Hiroichi; Sato, Tokijiro; Metoki, Hirobumi.

    1984-01-01

    Using a microcomputer, the locus and extent of the lesions, as demonstrated by computed tomography for 127 cases with various types of aphasia were superimposed onto standardized marices. The relationship between the foci of the lesions and the types of aphasia was investigated. Broca aphasics (n=39) : Since the accumulated site of the lesions highly involved the deep structures of the lower part of the precentral gyrus as well as the insula and lenticular nucleus, only 60% of the Broca aphasics had lesions on these areas. This finding has proved to have little localizing value. Wernicke aphasics (n=23) : The size of the lesion was significantly smaller than Broca's aphasia. At least 70% of the patients had the superior temporal lesions involving Wernicke's area and subcortical lesions of the superior and middle temporal gyri. Amnestic aphasics (n=18) : The size of the lesion was smaller than any other types. While there was some concentration of the lesions (maximum 40%) in the area of the subcortical region of the anterior temporal gyrus adjacent to Wernicke's area and the lenticular nucleus, the lesions were distributed throughout the left hemisphere. Amnestic aphasia was thought to be the least localizable. Conduction aphasics (n=11) : The lesions were relatively small in size. Many patients had posterior speech area lesions involving at least partially Wernicke's area. In particular, more than 80% of the conduction aphasics had lesions of the supramarginal gyrus and it's adjacent deep structures. Global aphasics (n=36) : In general, the size of the lesion was very large and 70% of the global aphasics had extensive lesions involving both Broca's and Wernicke's areas. However, there were observations showing that the lesions can be small and confined. (J.P.N.)

  12. 3-Bromopyruvate reverses hypoxia-induced pulmonary arterial hypertension through inhibiting glycolysis: In vitro and in vivo studies.

    Science.gov (United States)

    Chen, Fangzheng; Wang, Heng; Lai, Jiadan; Cai, Shujing; Yuan, Linbo

    2018-05-04

    Pulmonary arterial smooth muscle cell (PASMC) proliferation is vital to pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) pathogenesis, and inhibiting PASMC metabolism could serve as a new possible therapy to reverse the process. 3-Bromopyruvate (3-BrPA) is an effective glycolysis inhibitor with its effect in PAH remains unclear. Our study aims to assess the therapeutic effect of 3-BrPA in PAH rats and investigate the possible mechanism of 3-BrPA in PASMC proliferation and apoptosis. 27 healthy SD rats were grouped and treated with hypoxia/normoxia and administration of 3-BrPA/physiological saline. Mean pulmonary artery pressure (mPAP) and cardiac output (CO) were measured and pulmonary vascular resistance (PVR) was calculated. Right ventricular hypertrophy index (RVHI) was calculated to evaluate the right ventricular hypertrophy degree. The percentage of medial wall area (WA%) and medial wall thickness (WT%) were measured by image analysis. PASMCs groups received hypoxia/normoxia treatments and 3-BrPA/physiological saline. PASMC proliferation and migration were respectively detected by CCK-8 and cell wound scratch assay. Hexokinase II (HK-2) expression and lactate level were respectively measured by Western Blotting and lactate test kit to detect glycolysis. mPAP, PVR, PVHI, WA% and WT% in rats increased after the hypoxia treatment, but were lower compared to rats received 3-BrPA in hypoxia environment. HK-2 expression, lactate concentration, OD value and scratch areas in PASMCs increased after the hypoxia treatment, but were decreased after the administration of 3-BrPA. 3-BrPA can inhibit PASMC proliferation and migration by inhibiting glycolysis, and is effective in reversing the vascular remodeling in hypoxia-induced PAH rats. Copyright © 2017. Published by Elsevier B.V.

  13. Time and temperature affect glycolysis in blood samples regardless of fluoride-based preservatives: a potential underestimation of diabetes.

    Science.gov (United States)

    Stapleton, Mary; Daly, Niamh; O'Kelly, Ruth; Turner, Michael J

    2017-11-01

    Background The inhibition of glycolysis prior to glucose measurement is an important consideration when interpreting glucose tolerance tests. This is particularly important in gestational diabetes mellitus where prompt diagnosis and treatment is essential. A study was planned to investigate the effect of preservatives and temperature on glycolysis. Methods Blood samples for glucose were obtained from consented females. Lithium heparin and fluoride-EDTA samples transported rapidly in ice slurry to the laboratory were analysed for glucose concentration and then held either in ice slurry or at room temperature for varying time intervals. Paired fluoride-citrate samples were received at room temperature and held at room temperature, with analysis at similar time intervals. Results No significant difference was noted between mean glucose concentrations when comparing different sample types received in ice slurry. The mean glucose concentrations decreased significantly for both sets of samples when held at room temperature (0.4 mmol/L) and in ice slurry (0.2 mmol/L). A review of patient glucose tolerance tests reported in our hospital indicated that 17.8% exceeded the recommended diagnostic criteria for gestational diabetes mellitus. It was predicted that if the results of fasting samples were revised to reflect the effect of glycolysis at room temperature, the adjusted diagnostic rate could increase to 35.3%. Conclusion Preanalytical handling of blood samples for glucose analysis is vital. Fluoride-EDTA is an imperfect antiglycolytic, even when the samples are transported and analysed rapidly provides such optimal conditions. The use of fluoride-citrate tubes may offer a viable alternative in the diagnosis of diabetes mellitus.

  14. Blocking hexose entry into glycolysis activates alternative metabolic conversion of these sugars and upregulates pentose metabolism in Aspergillus nidulans

    Energy Technology Data Exchange (ETDEWEB)

    Khosravi, Claire; Battaglia, Evy; Kun, Roland S.; Dalhuijsen, Sacha; Visser, Jaap; Aguilar-Pontes, Maria V.; Zhou, Miamiao; Heyman, Heino M.; Kim, Young-Mo; Baker, Scott E.; de Vries, Ronald P.

    2018-03-22

    Background: Plant biomass is the most abundant carbon source for many fungal species. In the biobased industry fungi are used to produce lignocellulolytic enzymes to degrade agricultural waste biomass. Here we evaluated if it would be possible to create an Aspergillus nidulans strain that releases but does not metabolize hexoses from plant biomass. For this purpose, metabolic mutants were generated that were impaired in glycolysis, by using hexokinase (hxkA) and glucokinase (glkA) negative strains. To prevent repression of enzyme production due to the hexose accumulation, strains were generated that combined these mutations with a deletion in creA, the repressor involved in regulating preferential use of different carbon catabolic pathways. Results: Phenotypic analysis revealed reduced growth for the hxkA1 glkA4 mutant on wheat bran. However, hexoses did not accumulate during growth of the mutants on wheat bran, suggesting that glucose metabolism is re-routed towards alternative carbon catabolic pathways. The creAΔ4 mutation in combination with preventing initial phosphorylation in glycolysis resulted in better growth than the hxkA/glkA mutant and an increased expression of pentose catabolic and pentose phosphate pathway genes. This indicates that the reduced ability to use hexoses as carbon sources created a shift towards the pentose fraction of wheat bran as a major carbon source to support growth. Conclusion: Blocking the direct entry of hexoses to glycolysis activates alternative metabolic conversion of these sugars in A. nidulans during growth on plant biomass, but also upregulates conversion of other sugars, such as pentoses.

  15. A disappearing neonatal skin lesion.

    LENUS (Irish Health Repository)

    Hawkes, Colin Patrick

    2012-01-31

    A preterm baby girl was noted at birth to have a firm, raised, non-tender skin lesion located over her right hip. She developed three similar smaller lesions on her ear, buttock and right knee. All lesions had resolved by 2 months of age.

  16. Total Thyroidectomy

    Directory of Open Access Journals (Sweden)

    Lopez Moris E

    2016-06-01

    Full Text Available Total thyroidectomy is a surgery that removes all the thyroid tissue from the patient. The suspect of cancer in a thyroid nodule is the most frequent indication and it is presume when previous fine needle puncture is positive or a goiter has significant volume increase or symptomes. Less frequent indications are hyperthyroidism when it is refractory to treatment with Iodine 131 or it is contraindicated, and in cases of symptomatic thyroiditis. The thyroid gland has an important anatomic relation whith the inferior laryngeal nerve and the parathyroid glands, for this reason it is imperative to perform extremely meticulous dissection to recognize each one of these elements and ensure their preservation. It is also essential to maintain strict hemostasis, in order to avoid any postoperative bleeding that could lead to a suffocating neck hematoma, feared complication that represents a surgical emergency and endangers the patient’s life.It is essential to run a formal technique, without skipping steps, and maintain prudence and patience that should rule any surgical act.

  17. Lesiones deportivas Sports injuries

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Gallego Ching

    2007-04-01

    Full Text Available El estrés generado por la práctica deportiva ha originado una mayor probabilidad de que los atletas presenten lesiones agudas y crónicas. En el ámbito mundial existen diferentes investigaciones acerca de la incidencia de lesiones deportivas. La comparación de sus resultados es difícil por las diferencias en las características de la población y en la forma de reportar los datos, que varía ampliamente entre los estudios (proporciones o tasas de incidencia o tasas por cada 100 ó 1.000 participantes o tasas por horas de juego o por número de partidos jugados. Las tasas varían entre 1,7 y 53 lesiones por 1.000 horas de práctica deportiva, entre 0,8 y 90,9 por 1.000 horas de entrenamiento, entre 3,1 y 54,8 por 1.000 horas de competición y de 6,1 a 10,9 por 100 juegos. La gran variación entre las tasas de incidencia se explica por las diferencias existentes entre los deportes, los países, el nivel competitivo, las edades y la metodología empleada en los estudios. Se ha definido la lesión deportiva como la que ocurre cuando los atletas están expuestos a la práctica del deporte y se produce alteración o daño de un tejido, afectando el funcionamiento de la estructura. Los deportes de contacto generan mayor riesgo de presentar lesiones; se destacan al respecto los siguientes: fútbol, rugby, baloncesto, balonmano, artes marciales y jockey. Las lesiones ocurren con mayor probabilidad en las competencias que en el entrenamiento. Stress generated by sports practice has increased the probability that athletes suffer from acute and chronic injuries. Worldwide, there have been many different investigations concerning the incidence of sport injuries. The different ways in which results have been presented makes it difficult to compare among them. Rates of sports injuries vary between 1.7 and 53 per 1.000 hours of sports practice; 0.8 and 90.9 per 1.000 hours of training; 3.1 and 54.8 per 1.000 hours of competition, and 6.1 and 10.9 per 100

  18. Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non-small cell lung cancer cells.

    Science.gov (United States)

    Gao, Xiang; Han, Han

    2018-06-01

    Jolkinolide B (JB), a bioactive compound isolated from herbal medicine, has been found to inhibit tumor growth by altering glycolysis. However, whether glycolysis is influenced by JB in non-small cell lung cancer (NSCLC) cells and the mechanism remain unknown. The aim of the present study was to evaluate the effect of JB on the glycolysis in NSCLC cells and the underlying molecular mechanism. The results showed that JB treatment inhibited cell viability of A549 and H1299 cells in a concentration-dependent manner. JB reduced the glucose consumption, lactate production, and HK2 expression. The expressions of p-Akt and p-mTOR were also decreased by JB treatment. Knockdown of HK2 reduced glucose consumption and lactate production. Inhibition of the Akt/mTOR pathway decreased HK2 expression and inhibited glycolysis. In conclusion, the results indicated that JB inhibits glycolysis by down-regulating HK2 expression through inactivating the Akt/mTOR pathway in NSCLC cells, suggesting that JB might be a potential therapeutic agent for the treatment of NSCLC. © 2018 Wiley Periodicals, Inc.

  19. Analysis of pulmonary coin lesions

    International Nuclear Information System (INIS)

    Kim, O; Kim, K. H.; Oh, K. K.; Park, C. Y.

    1979-01-01

    For A long time the solitary pulmonary nodule has remained a difficult problem to solve and has attracted a great deal of attension in recent years. Circumscribed coin lesions of the lung were generally peripheral in location with respect to the pulmonary hilus. Because of this, important clinical problem in management and diagnosis arise. Such a lesion is discovered through roentgenologic examination. So the roentgenologists is the first be in a position to offer advise. This presentation is an attempt to correlate a useful diagnosis with roentgenologic findings of pulmonary coin lesion which enables us to get differential diagnosis of benign and malignant lesion. Histologically proven 120 cases of the pulmonary coin lesion during the period of 8 years were reviewed through plain film, tomogram, bronchoscopy, variable laboratory findings, and clinical history. The results are as follows: 1. Male to female sex ratio was 3 : 1. In age distribution, most of the malignant pulmonary coin lesion appeared in 6th decade (39%) and 5th decade (27%). In benign lesion, the most cases were in 3 rd decade. 2. Pathological cell type are as follows: Primary bronchogenic cancer 43.3%, tuberculoma 25.8%, inflammatory lesion 17.5%, benign tumor 10%, and bronchial adenoma, harmartoma, A.V. malformation, mesothelioma, are 1 case respectively. As a result benign and malignant lesion showed equal distribution (49.1% : 50.3%). 3. In symptom analysis ; cough is the most common (43.5%) symptom in malignant lesion, next follows hemoptysis (20.9%) and chest pain (14.5%). In benign lesion, most of the patient (32.7%) did not complain any symptom. 4. In malignant lesion, the most common nodular size was 4 cm (32.3%), and in benign lesion 2 cm sized coin was most common (39.3%). 5. In general, margin of nodule was very sharp and well demarcated in benign lesion (83.3%), and in malignant lesion that was less demarcated and poorly defined. 6. Most case of calcification (82.7%) was seen in benign

  20. Managing Carious Lesions

    DEFF Research Database (Denmark)

    Innes, N P T; Frencken, J E; Bjørndal, L

    2016-01-01

    Variation in the terminology used to describe clinical management of carious lesions has contributed to a lack of clarity in the scientific literature and beyond. In this article, the International Caries Consensus Collaboration presents 1) issues around terminology, a scoping review of current...... manifestations to the histopathology, we have based the terminology around the clinical consequences of disease (soft, leathery, firm, and hard dentine). Approaches to carious tissue removal are defined: 1)selective removal of carious tissue-includingselective removal to soft dentineandselective removal to firm...

  1. Vascular lesions following radiation

    International Nuclear Information System (INIS)

    Fajardo, L.F.; Berthrong, M.

    1988-01-01

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury

  2. Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

    Science.gov (United States)

    Shen, Yao; Tian, Yueyang; Shi, Xiaojie; Yang, Jianbo; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-08-01

    Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat.

    Science.gov (United States)

    Dimitriadis, G D; Leighton, B; Parry-Billings, M; West, D; Newsholme, E A

    1989-01-01

    1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations. PMID:2649073

  4. Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Goetze, K.; Meyer, S.S.; Mueller-Klieser, W. [University Medical Center Mainz Univ. (Germany). Inst. of Physiology and Pathophysiology; Yaromina, A. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Zips, D. [University Hospital Tuebingen (Germany). Dept. of Radiation Oncology; Baumann, M. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Dresden Technical Univ. Dresden (Germany). Dept. of Radiation Oncology

    2013-09-15

    Background and purpose: Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. Materials and methods: Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. Results: Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. Conclusion: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment. (orig.)

  5. HK2 Recruitment to Phospho-BAD Prevents Its Degradation, Promoting Warburg Glycolysis by Theileria-Transformed Leukocytes.

    Science.gov (United States)

    Haidar, Malak; Lombès, Anne; Bouillaud, Frédéric; Kennedy, Eileen J; Langsley, Gordon

    2017-03-10

    Theileria annulata infects bovine leukocytes, transforming them into invasive, cancer-like cells that cause the widespread disease called tropical theileriosis. We report that in Theileria-transformed leukocytes hexokinase-2 (HK2) binds to B cell lymphoma-2-associated death promoter (BAD) only when serine (S) 155 in BAD is phosphorylated. We show that HK2 recruitment to BAD is abolished by a cell-penetrating peptide that acts as a nonphosphorylatable BAD substrate that inhibits endogenous S155 phosphorylation, leading to complex dissociation and ubiquitination and degradation of HK2 by the proteasome. As HK2 is a critical enzyme involved in Warburg glycolysis, its loss forces Theileria-transformed macrophages to switch back to HK1-dependent oxidative glycolysis that down-regulates macrophage proliferation only when they are growing on glucose. When growing on galactose, degradation of HK2 has no effect on Theileria-infected leukocyte proliferation, because metabolism of this sugar is independent of hexokinases. Thus, targeted disruption of the phosphorylation-dependent HK2/BAD complex may represent a novel approach to control Theileria-transformed leukocyte proliferation.

  6. Regulation of the insulin-Akt signaling pathway and glycolysis during dehydration stress in the African clawed frog Xenopus laevis.

    Science.gov (United States)

    Wu, Cheng-Wei; Tessier, Shannon N; Storey, Kenneth B

    2017-12-01

    Estivation is an adaptive stress response utilized by some amphibians during periods of drought in the summer season. In this study, we examine the regulation of the insulin signaling cascade and glycolysis pathway in the African clawed frog Xenopus laevis during the dehydration stress induced state of estivation. We show that in the brain and heart of X. laevis, dehydration reduces the phosphorylation of the insulin growth factor-1 receptor (IGF-1R), and this is followed by similar reductions in the phosphorylation of the Akt and mechanistic target of rapamycin (mTOR) kinase. Interestingly, phosphorylation levels of IGF-1R and mTOR were not affected in the kidney, and phosphorylation levels of P70S6K and the ribosomal S6 protein were elevated during dehydration stress. Animals under estivation are also susceptible to periods of hypoxia, suggesting that glycolysis may also be affected. We observed that protein levels of many glycolytic enzymes remained unchanged during dehydration; however, the hypoxia response factor-1 alpha (HIF-1α) protein was elevated by greater than twofold in the heart during dehydration. Overall, we provide evidence that shows that the insulin signaling pathway in X. laevis is regulated in a tissue-specific manner during dehydration stress and suggests an important role for this signaling cascade in mediating the estivation response.

  7. Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways.

    Directory of Open Access Journals (Sweden)

    Yao Shen

    Full Text Available Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy.

  8. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

    2016-05-01

    Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

  9. Treatment of metastatic brain lesion

    Directory of Open Access Journals (Sweden)

    A. M. Zaytsev

    2015-01-01

    Full Text Available Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis.Material and method. In P. A. Hertsen Moscow Oncology Research Institute from 2007 to 2013 there were treated 268 patients with brain metastases. The mean age was 55.8 years (from 24 to 81 years. Metastases of colorectal cancer identified in 7.8%, cases of lung cancer in 34%, melanoma 9.3 %, breast cancer in 26%, kidney cancer in 11%, with non-identified primary tumor in 4.5%, other tumors accounted for 6.7%. Solitary metastasis was diagnosed in 164 (61,19% patients, oligometastasis (2-3 - 72 (26,87% patients with polymetastasis (more than 3 – 32 (11,94% patients. In 106 (39,55% of patients with brain metastases it was the only manifestation of the generalization process. To control the radical removal of the tumor in 93 (34,7% patients we used the method of fluorescence navigation (FN with the drug Alasens. In 66 (24,6% patients intraoperatively was held a session of photodynamic therapy (PDT. In 212 (79,1% cases, the removal of metastasis performed totally, 55 (20,9% patients stated Subtotal removal.Results. The observation period for the patients ranged from 3 to 79 months. Survival median among the entire group of patients with metastatic brain lesion was 12 months. Overall survival was significantly dependent on RPA class, the volume of postoperative treatment, histological type of primary tumor, number of intracerebral metastases and the timing of the relapse-free period.Conclusions. Factors that affects the overall survival are the features of the histology of the primary lesion, multiplicity of metastatic lesions, RPA class and the synchronous nature of the metastasis. The median of overall survival of patients who did not receive after surgical treatment of a particular type of therapy was only 4 months. If to use the combined treatment (surgical treatment with the irradiation of the whole brain median

  10. The metabolic impact of β-hydroxybutyrate on neurotransmission: Reduced glycolysis mediates changes in calcium responses and KATP channel receptor sensitivity

    DEFF Research Database (Denmark)

    Lund, Trine Meldgaard; Ploug, K.B.; Iversen, Anne

    2015-01-01

    -hydroxybutyrate might change neuronal function as there is a known coupling between metabolism and neurotransmission. The purpose of this study was to shed light on the effects of the ketone body β-hydroxybutyrate on glycolysis and neurotransmission in cultured murine glutamatergic neurons. Previous studies have shown...... an effect of β-hydroxybutyrate on glucose metabolism, and the present study further specified this by showing attenuation of glycolysis when β-hydroxybutyrate was present in these neurons. In addition, the NMDA receptor-induced calcium responses in the neurons were diminished in the presence of β...... to a combination of glucose and R-β-hydroxybutyrate in cultured neurons. Using the latter combination, glycolysis was diminished, NMDA receptor-induced calcium responses were lower, and the KATP channel blocker glibenclamide caused a higher transmitter release....

  11. Detection of Helicobacter pylori in Oral Lesions

    Directory of Open Access Journals (Sweden)

    Soussan Irani

    2013-12-01

    Full Text Available Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000. In addition, there was a statistically significant difference between the lesions examined (P=0.042. Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000, inside the blood vessels (P=0.003, inside the salivary gland duct (P=0.036, and muscle layer (P=0.122. Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested.

  12. Small white matter lesion detection in cerebral small vessel disease

    Science.gov (United States)

    Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

    2015-03-01

    Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

  13. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    International Nuclear Information System (INIS)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-01-01

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  14. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan, E-mail: moonsonlife@yahoo.com; Xian, Shulin; Lu, Yunfei, E-mail: doctorlife@126.com

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  15. Decreased hepatic response to glucagon, adrenergic agonists, and cAMP in glycogenolysis, gluconeogenesis, and glycolysis in tumor-bearing rats.

    Science.gov (United States)

    Biazi, Giuliana R; Frasson, Isabele G; Miksza, Daniele R; de Morais, Hely; de Fatima Silva, Flaviane; Bertolini, Gisele L; de Souza, Helenir M

    2018-05-15

    The response to glucagon and adrenaline in cancer cachexia is poorly known. The aim of this study was to investigate the response to glucagon, adrenergic agonists (α and β) and cyclic adenosine monophosphate (cAMP) on glycogenolysis, gluconeogenesis, and glycolysis in liver perfusion of Walker-256 tumor-bearing rats with advanced cachexia. Liver ATP content was also investigated. Rats without tumor (healthy) were used as controls. Agonists α (phenylephrine) and β (isoproterenol) adrenergic, instead of adrenaline, and cAMP, the second messenger of glucagon and isoproterenol, were used in an attempt to identify mechanisms involved in the responses. Glucagon (1 nM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in the liver of healthy and tumor-bearing rats, but their effects were lower in tumor-bearing rats. Isoproterenol (20 µM) stimulated glycogenolysis, gluconeogenesis, and glycolysis in healthy rats and had virtually no effect in tumor-bearing rats. cAMP (9 µM) also stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in healthy rats but had practically no effect in tumor-bearing rats. Phenylephrine (2 µM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis and these effects were also lower in tumor-bearing rats than in healthy. Liver ATP content was lower in tumor-bearing rats. In conclusion, tumor-bearing rats with advanced cachexia showed a decreased hepatic response to glucagon, adrenergic agonists (α and β), and cAMP in glycogenolysis, gluconeogenesis, and glycolysis, which may be due to a reduced rate of regulatory enzyme phosphorylation caused by the low ATP levels in the liver. © 2018 Wiley Periodicals, Inc.

  16. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C

    2015-01-01

    10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current......BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants...... associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from...

  17. Management of Preinvasive Lesions.

    Science.gov (United States)

    Patrono, Maria G; Corzo, Camila; Iniesta, Maria; Ramirez, Pedro T

    2017-12-01

    Serous tubal intraepithelial carcinoma is considered the precursor lesion of high-grade serous carcinoma, and found in both low-risk and high-risk populations. Isolated serous tubal intraepithelial carcinomas in patients with BRCA1/2 mutations are detected in ∼2% of patients undergoing risk-reducing bilateral salpingo-oophorectomy and even with removal of the tubes and ovaries the rate of developing primary peritoneal carcinoma following remains up to 7.5%. Postoperative recommendations after finding incidental STICs remain unclear and surgical staging, adjuvant chemotherapy, or observation have been proposed. Discovery of STIC should prompt consideration of hereditary cancer program referral for BRCA1/2 mutation screening.

  18. Combined Hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (HyperPET) Estimates of Glycolysis in Canine Cancer Patients

    DEFF Research Database (Denmark)

    Hansen, Adam E.; Gutte, Henrik; Holst, Pernille

    2018-01-01

    13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpol......13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare...

  19. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here

  20. Reassessment of FDG uptake in tumor cells: High FDG uptake as a reflection of oxygen-independent glycolysis dominant energy production

    Energy Technology Data Exchange (ETDEWEB)

    Waki, A.; Fujibayashi, Y.; Yonekura, Y.; Sadato, N.; Ishii, Y.; Yokoyama, A

    1997-10-01

    To determine appropriate use of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of malignant tumors, the mechanism of enhanced FDG uptake in tumor cells was reassessed using in vitro cultured cell lines and {sup 3}H-deoxyglucose (DG), in combination with possible parameters of aerobic and anaerobic energy production. The high DG uptake in the tumor cells reflected the dependency of energy production on anaerobic glycolysis, and paradoxically on low levels of aerobic oxidative phosphorylation in mitochondria. We discuss here factors underlying anaerobic glycolysis in tumor cells.

  1. CLINICOPATHOLOGICAL STUDY OF PAPULOSQUAMOUS SKIN LESIONS

    Directory of Open Access Journals (Sweden)

    Chowdari Balaji

    2018-02-01

    Full Text Available BACKGROUND Papulosquamous lesions form the largest group of skin diseases. Since, they are all characterized by scaling papules or plaques, clinical confusion may result in their diagnosis, hence definitive histopathological analysis is important for their differentiation. MATERIALS AND METHODS The study includes skin biopsies from 108 clinically diagnosed /suspected non-infectious, erythematous, papulosquamous skin diseases which were received in the Department of Pathology, Andhra Medical College, Visakhapatnam for a period of two years from January 2016 to December 2017. The specimens obtained were subjected to formalin fixation and was subjected to routine processing and sections were stained with haematoxylin and eosin (H&E. The lesions were classified as Lichen Planus, Psoriasis, along with rare conditions like Pityriasis Rosea, Parapsoriasis, Pityriasis Rubra Pilaris, Prurigo Nodularis and Lichen Simplex chronicus and clinicopathological correlation was done. RESULTS A total of 108 cases were studied. Lichen planus (51 cases- 47.22% was the most common lesions followed by Psoriasis (34 cases - 31.48% and with majority of cases in the age group of 21 to 30 years (25 cases– 23.15%. Females were more commonly affected with a male to female ratio of 0.89:1. Out of 108 cases, clinicopathological correlation was seen in 68 cases (62.96%. CONCLUSION The importance of specific histopathological diagnosis lies in distinguishing these lesions into different entities as the treatment and prognosis varies widely and is disease-specific.

  2. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  3. US and CT findings in splenic focal lesions in AIDS

    International Nuclear Information System (INIS)

    Schinina, V.; Rizzi, E.B.; Mazzuoli, G.; Bibbolilno, C.; David, V.

    2000-01-01

    To evaluate the role of US and CT in focal splenic lesions in AIDS patients in relation to etiology. Material and Methods: A total of 66 patients with AIDS and focal splenic lesions were examined with sonography. CT with administration of contrast medium was performed in 12 cases. Results: Of the focal splenic lesions, 67% were correlated with an infective pathology with prevalence of Mycobacteria tuberculosis (75%), 26% were neoplastic and 6% splenic infarcts. The lesions were hypoechoic in 60% of the cases, while 10% were hypoanechoic and 1% anechoic. At CT, all lesions appeared hypodense, even after i.v. administration of contrast medium. Conclusion: The combination of echographic reports and clinical and laboratory data allows for a diagnosis that can be confirmed, and making a decision for effective therapy of AIDS is possible. CT does not provide any additional information

  4. Biopsy results of Bosniak 2F and 3 cystic lesions

    DEFF Research Database (Denmark)

    Rasmussen, René; Hørlyck, Arne; Nielsen, Tommy Kjærgaard

    be helpful in clinical decisions. Material and Methods: From March 2013 - December 2014 a total of 295 percutaneous ultrasound guided biopsies from 287 patients with a suspected malignant renal lesion were performed at our institution. All cases were reviewed in PACS by (RR) and lesions presenting...... with a cystic change were re-evaluated and re-categorized after the Bosniak classification system. The re-evaluation and re-categorization was performed in consensus by a junior radiologist (RR) and an uro-radiological expert (OG). Results: Biopsies from eighteen Bosniak 2F cystic lesions were pathologically...... analyzed and three (17%) proved to be malignant. Biopsies from seventeen Bosniak 3 cystic lesions were pathologically analyzed and five (29%) were found to be malignant. Conclusion: Our results reveal a considerable malignancy rate among both Bosniak 2F and 3 cystic renal lesions. Biopsy seems...

  5. Correlation between clinical and histopathological diagnoses in periapical inflammatory lesions.

    Science.gov (United States)

    Diegues, Liliane Lopes; Colombo Robazza, Carlos Roberto; Costa Hanemann, João Adolfo; Costa Pereira, Alessandro Antônio; Silva, Cléverson O

    2011-08-01

      The purpose of the present study was to evaluate the correlation between clinical and histopathological diagnoses of periapical inflammatory lesions, focusing mainly on cystic conditions.   Files dating from 1998 to 2006 at the Oral Pathology Laboratory, School of Dentistry, Alfenas Federal University, Brazil, were reviewed to identify cases with histopathological diagnoses of periapical inflammatory lesions. A total of 1788 files were analyzed, and 255 cases were identified with clinical diagnoses of periapical inflammatory lesions.   The most prevalent clinical diagnosis was apical periodontal cyst (59%), followed by periapical granuloma (20%), and dentoalveolar abscess (2%). After histopathological analysis, 53% of the cases represented apical periodontal cyst, 42% periapical granuloma, and 5% dentoalveolar abscess.   The outcomes of the present study show a high prevalence of periapical cysts among periapical inflammatory lesions. Moreover, this study highlights the importance of histopathological evaluation for the correct diagnosis of periapical inflammatory lesions. © 2011 Blackwell Publishing Asia Pty Ltd.

  6. Prognosis in aphasia and CT localization and lesion size

    International Nuclear Information System (INIS)

    Hojo, Kei; Watanabe, Shunzo; Tasaki, Hiroichi; Sato, Tokijiro; Metoki, Hirofumi.

    1985-01-01

    The influence of CT localization and lesion size on the prognosis of aphasia was studied in 76 right-handed aphasic patients who had had a cerebrovascular accident. On the basis of the results of the accumulated lesions with many Broca and Wernicke aphasics, the highly involved sites were determined to be the Broca area and the Wernicke area. The CT lesions of 76 aphasics were traced in the total area, the Broca area, and the Wernicke area; these were termed the total lesion, the Broca lesion, and the Wernicke lesion respectively. The digitizer program was used to determine the size of the lesions by tracing them onto standardized martrices, which were divided into 3000 points and which corresponded to the CT slices. The recovery rates were determined by comparing the scores of 2 SLTA (Standard Language Test of Aphasia) tests given at 3-month intervals in order to coincide with the clinical impressions. These recovery rates were used as an indication of the prognosis. The results obtained were as follows: (1) Negative correlations between the sizes of the total area and the Broca area and the recovery rates were observed, while no correlation was observed between the size of the Wernicke area and the recovery rates. These findings indicate that the larger the lesions in the total area and the Broca area, the less overall recovery occurs in the total language deficit. (2) Negative correlations between the size of each area and the recovery rates in expressive aspects, namely, ''speaking'' and ''writing,'' were observed, but not in the receptive aspects, namely, ''hearing'' and ''reading,'' or in ''calculation.'' (author)

  7. NaCl stress impact on the key enzymes in glycolysis from Lactobacillus bulgaricus during freeze-drying.

    Science.gov (United States)

    Li, Chun; Sun, Jinwei; Qi, Xiaoxi; Liu, Libo

    2015-01-01

    The viability of Lactobacillus bulgaricus in freeze-drying is of significant commercial interest to dairy industries. In the study, L.bulgaricus demonstrated a significantly improved (p enzymes in glycolysis during 2% NaCl stress were studied. NaCl stress significantly enhanced (p enzymes (phosphofructokinase, pyruvate kinase, and lactate dehydrogenase) decreased during freeze-drying, and NaCl stress were found to improve activities of these enzymes before and after freeze-drying. However, a transcriptional analysis of the corresponding genes suggested that the effect of NaCl stress on the expression of the pfk2 gene was not obvious. The increased survival of freeze-dried cells of L. bulgaricus under NaCl stress might be due to changes in only the activity or translation level of these enzymes in different environmental conditions but have no relation to their mRNA transcription level.

  8. Clinical analysis of bone scanning in solitary lesion

    International Nuclear Information System (INIS)

    Zhu Jun; Zhu Ruisen; Zhu Jifang

    2002-01-01

    A rational analysis procedure for solitary lesions on whole bone scanning was offered. This study was undertaken to analyze retrospectively solitary lesions which obtained final diagnose through the following aspects: (1) diagnosis of bone metastasis, (2) the incidence of bone metastasis in different tumor, (3) the most possible lesion sites indicating bone metastasis, (4) morphological analysis of solitary lesions. The results are: (1) The incidence of solitary lesions in 2465 cases on whole bone scanning is 15.3%. (2) The rate of bone metastasis is 24.8% in 282 patients with primary malignancy. The rate of bone metastasis of 6.3% in 64 patients without primary malignancy, and the total diagnostic rate of bone metastasis is 21.4% in 346 patients. (3) In patients with primary malignancy, the incidence of bone metastasis of solitary lesions is as follows respectively; bronchi cancer 36.1%(22/61); breast cancer 23.8%(20/84); prostate gland 17.2%(5/29); other urinary system cancer 22.2%(4/18); G.I. system cancer 16.9%(10/59); others 29.0%(9/31). There is no significant difference in different cancer. (4) In patients without primary malignancy, 93.7%(60/64) of solitary lesions are benign. (5) From anatomical point of view, the authors found the diagnostic rate of bone metastasis is as follow: 30% in spine; 34.2% in pelvis; 36.4% in skull; 10.8% in other bones. There are significant differences in four groups. It is concluded that: (1) The diagnostic rate of bone metastasis in solitary lesions is 21.4%. (2) The most possible solitary lesions indicating osseous tumor spread are at spine, pelvic and skull. (3) Special attention to 'cold' and streak like lesions should be paid. (4) A clinical analysis procedure for diagnosis of solitary lesions has been summarized out here

  9. Infected Atopic Dermatitis Lesions Contain Pharmacologic Amounts of Lipoteichoic Acid

    Science.gov (United States)

    Travers, Jeffrey B.; Kozman, Amal; Mousdicas, Nico; Saha, Chandan; Landis, Megan; Al-Hassani, Mohammed; Yao, Weiguo; Yao, Yongxue; Hyatt, Ann-Marie; Sheehan, Michael P.; Haggstrom, Anita N.; Kaplan, Mark H.

    2009-01-01

    Background Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown. Objective We sought to characterize the amounts of the biologically active bacterial lipoprotein lipoteichoic acid (LTA) in infected AD lesions. Methods Eighty-nine children with clinically impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index (EASI), and then wash fluid obtained from the lesion for quantitative bacterial culture, and measurement of LTA and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities. The patients were treated with a regimen that included topical corticosteroids and systemic antibiotics and the lesion was re-analyzed after two weeks. Results S. aureus was identified in 79 of 89 children enrolled in the study. The bacterial CFU correlated with the EASI lesional score (p = 0.04). LTA levels up to 9.8 μg/ml were measured in the wash fluid samples and the amounts correlated with the lesional EASI scores (p = 0.01) and S. aureus CFU (p < 0.001). Approximately 30% of clinically impetiginized AD lesions contained greater than 1 μg/ml LTA, amounts that exert effects on various cell types in vitro. Moreover, injection of skin tissue ex vivo with amounts of LTA found in AD lesions resulted in epidermal cytokine gene expression. Conclusions Pharmacologic levels of LTA are found in many infected atopic dermatitis lesions. Clinical Implications These findings suggest that staphylococcal LTA could be an important mediator of the increased skin inflammation associated with infected AD. Capsule Summary These studies demonstrate high levels of staphylococcal LTA are found on impetiginized AD lesions. Moreover, subjects harboring MRSA exhibited greater total body involvement of AD. PMID:19962742

  10. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Simultaneous stimulation of glycolysis and gluconeogenesis by feeding in the anterior intestine of the omnivorous GIFT tilapia, Oreochromis niloticus

    Directory of Open Access Journals (Sweden)

    Yong-Jun Chen

    2017-06-01

    Full Text Available The present study was performed to investigate the roles of anterior intestine in the postprandial glucose homeostasis of the omnivorous Genetically Improved Farmed Tilapia (GIFT. Sub-adult fish (about 173 g were sampled at 0, 1, 3, 8 and 24 h post feeding (HPF after 36 h of food deprivation, and the time course of changes in intestinal glucose transport, glycolysis, glycogenesis and gluconeogenesis at the transcription and enzyme activity level, as well as plasma glucose contents, were analyzed. Compared with 0 HPF (fasting for 36 h, the mRNA levels of both ATP-dependent sodium/glucose cotransporter 1 and facilitated glucose transporter 2 increased during 1-3 HPF, decreased at 8 HPF and then leveled off. These results indicated that intestinal uptake of glucose and its transport across the intestine to blood mainly occurred during 1-3 HPF, which subsequently resulted in the increase of plasma glucose level at the same time. Intestinal glycolysis was stimulated during 1-3 HPF, while glucose storage as glycogen was induced during 3-8 HPF. Unexpectedly, intestinal gluconeogenesis (IGNG was also strongly induced during 1-3 HPF at the state of nutrient assimilation. The mRNA abundance and enzyme activities of glutamic-pyruvic and glutamic-oxaloacetic transaminases increased during 1-3 HPF, suggesting that the precursors of IGNG might originate from some amino acids. Taken together, it was concluded that the anterior intestine played an important role in the regulation of postprandial glucose homeostasis in omnivorous tilapia, as it represented significant glycolytic potential and glucose storage. It was interesting that postprandial IGNG was stimulated by feeding temporarily, and its biological significance remains to be elucidated in fish.

  12. Intense light-elicited upregulation of miR-21 facilitates glycolysis and cardioprotection through Per2-dependent mechanisms.

    Directory of Open Access Journals (Sweden)

    Colleen Marie Bartman

    Full Text Available A wide search for ischemic preconditioning (IPC mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2 to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs. One prominent result of our in silico analysis for cardiac Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation of hypoxia and metabolic pathways. Based on this Per2 dependency, we subsequently found a diurnal expression pattern for miR-21 with higher miR-21 expression levels at Zeitgeber time (ZT 15 compared to ZT3. Gain or loss of function studies for miR-21 using miRNA mimics or miRNA inhibitors and a Seahorse Bioanalyzer uncovered a critical role of miR-21 for cellular glycolysis, glycolytic capacity, and glycolytic reserve. Exposing mice to intense light, a strategy to induce Per2, led to a robust induction of cardiac miR-21 tissue levels and decreased infarct sizes, which was abolished in miR-21-/- mice. Similarly, first translational studies in humans using intense blue light exposure for 5 days in healthy volunteers resulted in increased plasma miR-21 levels which was associated with increased phosphofructokinase activity, the rate-limiting enzyme in glycolysis. Together, we identified miR-21 as cardioprotective downstream target of Per2 and suggest intense light therapy as a potential strategy to enhance miR-21 activity and subsequent carbohydrate metabolism in humans.

  13. Simultaneous stimulation of glycolysis and gluconeogenesis by feeding in the anterior intestine of the omnivorous GIFT tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Chen, Yong-Jun; Zhang, Ti-Yin; Chen, Hai-Yan; Lin, Shi-Mei; Luo, Li; Wang, De-Shou

    2017-06-15

    The present study was performed to investigate the roles of anterior intestine in the postprandial glucose homeostasis of the omnivorous Genetically Improved Farmed Tilapia (GIFT). Sub-adult fish (about 173 g) were sampled at 0, 1, 3, 8 and 24 h post feeding (HPF) after 36 h of food deprivation, and the time course of changes in intestinal glucose transport, glycolysis, glycogenesis and gluconeogenesis at the transcription and enzyme activity level, as well as plasma glucose contents, were analyzed. Compared with 0 HPF (fasting for 36 h), the mRNA levels of both ATP-dependent sodium/glucose cotransporter 1 and facilitated glucose transporter 2 increased during 1-3 HPF, decreased at 8 HPF and then leveled off. These results indicated that intestinal uptake of glucose and its transport across the intestine to blood mainly occurred during 1-3 HPF, which subsequently resulted in the increase of plasma glucose level at the same time. Intestinal glycolysis was stimulated during 1-3 HPF, while glucose storage as glycogen was induced during 3-8 HPF. Unexpectedly, intestinal gluconeogenesis (IGNG) was also strongly induced during 1-3 HPF at the state of nutrient assimilation. The mRNA abundance and enzyme activities of glutamic-pyruvic and glutamic-oxaloacetic transaminases increased during 1-3 HPF, suggesting that the precursors of IGNG might originate from some amino acids. Taken together, it was concluded that the anterior intestine played an important role in the regulation of postprandial glucose homeostasis in omnivorous tilapia, as it represented significant glycolytic potential and glucose storage. It was interesting that postprandial IGNG was stimulated by feeding temporarily, and its biological significance remains to be elucidated in fish. © 2017. Published by The Company of Biologists Ltd.

  14. Preoperative nonpalpable breast lesions localization

    Energy Technology Data Exchange (ETDEWEB)

    Gardellin, G; Natale, F; Perin, B

    1986-01-01

    The effectiveness of real time sonography and mammography are examined in localizing with a hookwire (introduced via a straight needle) the nonpalpable breast lesions. The method, used for surgery or biopsy, was successful in a series of 13 patients with nonpalpable breast lesions, 4 affectd by carcinoma. 18 refs.

  15. Characteristics, Detection Methods and Treatment of Questionable Occlusal Carious Lesions

    DEFF Research Database (Denmark)

    Makhija, S.K.; Gilbert, G.H.; Funkhouser, E.

    2014-01-01

    . The objective of this report has been to quantify the characteristics of these common lesions, the diagnostic aids used and the treatment of QOC. A total of 82 dentist and hygienist practitioner-investigators from the USA and Denmark in the National Dental Practice-Based Research Network participated. When...... consenting patients presented with a QOC, information was recorded about the patient, tooth, lesion and treatments. A total of 2,603 QOC from 1,732 patients were analyzed. The lesions were usually associated with a fissure, on molars, and varied from yellow to black in color. Half presented with a chalky...... luster and had a rough surface when examined with an explorer. There was an association between color and luster: 10% were chalky-light, 47% were shiny-dark and 42% were mixtures. A higher proportion of chalky than of shiny lesions were light (22 vs. 9%; p color were less common...

  16. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.

    Science.gov (United States)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Adaptation to the coupling of glycolysis to toxic methylglyoxal production in tpiA deletion strains of Escherichia coli requires synchronized and counterintuitive genetic changes

    DEFF Research Database (Denmark)

    McCloskey, Douglas; Xu, Sibei; Sandberg, Troy E.

    2018-01-01

    -talk between carbon starvation and inorganic phosphate signalling was revealed in the tpiA deletion strain that required mutations in inorganic phosphate signalling mechanisms to alleviate; and 3) The split flux through lower glycolysis depleted glycolytic intermediates requiring a host of synchronized...

  18. The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis

    International Nuclear Information System (INIS)

    Brighenti, Elisa; Carnicelli, Domenica; Brigotti, Maurizio; Fiume, Luigi

    2017-01-01

    Most cancer cells use aerobic glycolysis to fuel their growth and many efforts are made to selectively block this metabolic pathway in cancer cells by inhibiting lactate dehydrogenase A (LDHA). However, LDHA is a moonlighting protein which exerts functions also in the nucleus as a factor associated to transcriptional complexes. Here we found that two small molecules which inhibit the enzymatic activity of LDHA hinder the transcription of histone 2B gene independently from the block of aerobic glycolysis. Moreover, we observed that silencing this gene reduces cell replication, hence suggesting that the inhibition of LDHA can also affect the proliferation of normal non-glycolysing dividing cells. - Highlights: • Blocking aerobic glycolysis is an approach to impair proliferation of cancer cells. • Small inhibitors of LDHA block aerobic glycolysis. • LDHA is also involved in the transcription of histone 2B gene. • LDHA inhibitors block histone 2B transcription. • LDHA inhibitors can hinder the proliferation also of non-glycolysing normal cells.

  19. Creatine Monohydrate Enhances Energy Status and Reduces Glycolysis via Inhibition of AMPK Pathway in Pectoralis Major Muscle of Transport-Stressed Broilers.

    Science.gov (United States)

    Zhang, Lin; Wang, Xiaofei; Li, Jiaolong; Zhu, Xudong; Gao, Feng; Zhou, Guanghong

    2017-08-16

    Creatine monohydrate (CMH) contributes to reduce transport-induced muscle rapid glycolysis and improve meat quality of broilers, but the underlying mechanism is still unknown. Therefore, this study aimed to investigate the molecular mechanisms underlying the ameliorative effects of CMH on muscle glycolysis metabolism of transported broilers during summer. The results showed that 3 h transport during summer elevated chicken live weight loss and plasma corticosterone concentration; decreased muscle concentrations of ATP, creatine, and energy charge value; increased muscle AMP concentration and AMP/ATP ratio; and upregulated muscle mRNA expression of LKB1 and AMPKα2, as well as protein expression of p-LKB1 Thr189 and p-AMPKα Thr172 , which subsequently resulted in rapid glycolysis in the pectoralis major muscle and consequent reduction of meat quality. Dietary addition of CMH at 1200 mg/kg ameliorated transport-induced rapid muscle glycolysis and reduction of meat quality via enhancement of the energy-buffering capacity of intramuscular phosphocreatine/creatine system and inhibition of AMPK pathway.

  20. Hypoxia-inducible transcription factor-1α promotes hypoxia-induced A549 apoptosis via a mechanism that involves the glycolysis pathway

    International Nuclear Information System (INIS)

    Luo, FengMing; Liu, XiaoJing; Yan, NaiHong; Li, ShuangQing; Cao, GuiQun; Cheng, QingYing; Xia, QingJie; Wang, HongJing

    2006-01-01

    Hypoxia-inducible transcription factor-1α (HIF-1α), which plays an important role in controlling the hypoxia-induced glycolysis pathway, is a 'master' gene in the tissue hypoxia response during tumor development. However, its role in the apoptosis of non-small cell lung cancer remains unknown. Here, we have studied the effects of HIF-1α on apoptosis by modulating HIF-1α gene expression in A549 cells through both siRNA knock-down and over-expression. A549 cells were transfected with a HIF-1α siRNA plasmid or a HIF-1α expression vector. Transfected cells were exposed to a normoxic or hypoxic environment in the presence or absence of 25 mM HEPES and 2-deoxyglucose (2-DG) (5 mM). The expression of three key genes of the glycolysis pathway, glucose transporter type 1(GLUT1), phosphoglycerate kinase 1(PGK1), and hexokinase 1(HK1), were measured using real-time RT-PCR. Glycolysis was monitored by measuring changes of pH and lactate concentration in the culture medium. Apoptosis was detected by TUNEL assay and flow cytometry. Knocking down expression of HIF-1α inhibited the glycolysis pathway, increased the pH of the culture medium, and protected the cells from hypoxia-induced apoptosis. In contrast, over-expression of HIF-1α accelerated glycolysis in A549 cells, decreased the pH of the culture medium, and enhanced hypoxia-induced apoptosis. These effects of HIF-1α on glycolysis, pH of the medium, and apoptosis were reversed by treatment with the glycolytic inhibitor, 2-DG. Apoptosis induced by HIF-1α over-expression was partially inhibited by increasing the buffering capacity of the culture medium by adding HEPES. During hypoxia in A549 cells, HIF-1α promotes activity of the glycolysis pathway and decreases the pH of the culture medium, resulting in increased cellular apoptosis

  1. RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis

    Science.gov (United States)

    Huang, Peng; Chang, Shi; Jiang, Xiaolin; Su, Juan; Dong, Chao; Liu, Xu; Yuan, Zhengtai; Zhang, Zhipeng; Liao, Huijun

    2015-01-01

    A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma. PMID:25755717

  2. Changing activity in MS lesions

    International Nuclear Information System (INIS)

    Kermode, A.G.; Tofts, P.S.; Thompson, A.J.; Rudge, P.; MacManus, D.G.; Kendall, B.E.; Moseley, I.F.; Kingsley, D.P.E.; McDonald, W.I.

    1989-01-01

    Gd-DTPA enhanced T1 weighted MRI is a discriminating test for a defective blood-brain barrier, with MS lesions showing considerable variation in the pattern of enhancement. Since little is known of the changes in the blood-brain barrier in the active plaque over time, the natural history of blood-brain barrier disturbance in the MS lesion was examined to confirm earlier reports that Gd-DTPA enhancement is a consistent early event in new lesions of relapsing/remitting MS. This knowledge is essential for the use of MRI in monitoring treatment. (author). 9 refs

  3. PHAEOHYPHOMYCOSIS: CUTANEOUS, SUBCUTANEOUS, NASOPHARYNGEAL LESIONS

    Directory of Open Access Journals (Sweden)

    M. Rasoolinejad

    1999-06-01

    Full Text Available Phaeohyphomycosis is an amalgam of clinical diseases caused by a wide variety of dematiaceous fungi. We are reporting on a 16 year-old patient from Amol with subcutaneous cervical nodes and nasopharyngeal lesions of phaeohypho"nmycosis that were confirmed by pathological examination, direct smear, and culture. After treatment with an oral triazole (Itraconazole for 4 months, all nodes and lesions disappeared and treatment was stopped A new lesion appeared on his chest wall 8 months, therapy with itraconazole was restarted and commuted for a long time.

  4. OCT investigation of dental lesions

    Science.gov (United States)

    Osiac, Eugen; Popescu, Sanda Mihaela; Scrieciu, Monica; Mercuţ, Rǎzvan; Mercuţ, Veronica; Vǎtu, Mihaela

    2018-03-01

    There are several important non carious lesions affecting the tooth structure, lesions which may be classified into four clinical forms of dental wear: abfraction, erosion, attrition and abrasion, and different types of root resorption. Search for new, non-invasive and fast methods able to detect and describe such injuries is of utmost importance. Optical coherence tomography (OCT) proved itself as an appropriate investigation method for several medical fields including ophthalmology, dermatology, cardiology etc. Our study reveals OCT preliminary investigations as a promising tool for detecting and evaluating of the mentioned lesions.

  5. Determination of lesion size by ultrasound during radiofrequency catheter ablation.

    Science.gov (United States)

    Awad, S; Eick, O

    2003-01-01

    The catheter tip temperature that is used to control the radiofrequency generator output poorly correlates to lesion size. We, therefore, evaluated lesions created in vitro using a B-mode ultrasound imaging device as a potential means to assess lesion generation during RF applications non-invasively. Porcine ventricular tissue was immersed in saline solution at 37 degrees C. The catheter was fixed in a holder and positioned in a parallel orientation to the tissue with an array transducer (7.5 MHz) app. 3 cm above the tissue. Lesions were produced either in a temperature controlled mode with a 4-mm tip catheter with different target temperatures (50, 60, 70 and 80 degrees C, 80 W maximum output) or in a power controlled mode (25, 50 and 75 W, 20 ml/min irrigation flow) using an irrigated tip catheter. Different contact forces (0.5 N, 1.0 N) were tested, and RF was delivered for 60 s. A total of 138 lesions was produced. Out of these, 128 could be identified on the ultrasound image. The lesion depth and volume was on average 4.1 +/- 1.6 mm and 52 +/- 53 mm3 as determined by ultrasound and 3.9 +/- 1.7 mm and 52 +/- 55 mm3 as measured thereafter, respectively. A linear correlation between the lesion size determined by ultrasound and that measured thereafter was demonstrated with a correlation coefficient of r = 0.87 for lesion depth and r = 0.93 for lesion volume. We conclude that lesions can be assessed by B-mode ultrasound imaging.

  6. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class......Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can...... be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical...

  7. MRI atlas of MS lesions

    Energy Technology Data Exchange (ETDEWEB)

    Sahraian, Mohammad Ali [Tehran Univ. of Medical Sciences Sina Hospital (Iran). Dept. of Neurology; Radue, Ernst-Wilhelm [Univ. Hospital Basel (Switzerland). Dept. of Neuroradiology

    2008-07-01

    MRI has become the main paraclinical test in the diagnosis and management of multiple sclerosis. We have demonstrated more than 400 pictures of different typical and atypical MS lesions in this atlas. Each image has a teaching point. New diagnostic criteria and differential diagnosis are discussed and the book is supported by a teaching DVD where the reader can see MS lesions in different slices and sequences. (orig.)

  8. Cystic lesion around the hip joint

    Science.gov (United States)

    Yukata, Kiminori; Nakai, Sho; Goto, Tomohiro; Ikeda, Yuichi; Shimaoka, Yasunori; Yamanaka, Issei; Sairyo, Koichi; Hamawaki, Jun-ichi

    2015-01-01

    This article presents a narrative review of cystic lesions around the hip and primarily consists of 5 sections: Radiological examination, prevalence, pathogenesis, symptoms, and treatment. Cystic lesions around the hip are usually asymptomatic but may be observed incidentally on imaging examinations, such as computed tomography and magnetic resonance imaging. Some cysts may enlarge because of various pathological factors, such as trauma, osteoarthritis, rheumatoid arthritis, or total hip arthroplasty (THA), and may become symptomatic because of compression of surrounding structures, including the femoral, obturator, or sciatic nerves, external iliac or common femoral artery, femoral or external iliac vein, sigmoid colon, cecum, small bowel, ureters, and bladder. Treatment for symptomatic cystic lesions around the hip joint includes rest, nonsteroidal anti-inflammatory drug administration, needle aspiration, and surgical excision. Furthermore, when these cysts are associated with osteoarthritis, rheumatoid arthritis, and THA, primary or revision THA surgery will be necessary concurrent with cyst excision. Knowledge of the characteristic clinical appearance of cystic masses around the hip will be useful for determining specific diagnoses and treatments. PMID:26495246

  9. Transarterial embolization in head and neck lesions

    International Nuclear Information System (INIS)

    Chang, Kee Hyun; Han, Man Chung

    1985-01-01

    The transarterial embolization procedures have been performed in a total of 38 patients with head and neck lesions, including 5 carotid-cavernous fistulas, 1 internal carotid aneurysm, 10 meningiomas, 16 nasopharyngeal angiofibromas, 1 post-traumatic epistaxis and 5 other vascular tumors, over the 18 months-period. Six cases of C-C fistula and ICA aneurysm were treated with the detachable balloon catheter technique. The meningiomas, angiofibromas and all other lesions were embolized with superselection of the branches of the external carotid artery such as the internal maxillary, the middle meningeal, the ascending pharyngeal the facial or other branches, using Berenstein superselective catheters or conventional angiographic catheters. The PVA (polyvinyl alcohol foam) and/or Gelfoam particles were used as embolic materials in these cases. Most of the lesions were successfully embolized with minor transient complications such as pain, headache, vomiting, fever and etc. But in 4 cases occurred the serious complications; one cerebral hemorrhage, two cerebral infarctions, and one acute laryngeal edema. The selection of the embolic materials and the catheters, and the complications are briefly discussed

  10. Transarterial embolization in head and neck lesions

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kee Hyun; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1985-06-15

    The transarterial embolization procedures have been performed in a total of 38 patients with head and neck lesions, including 5 carotid-cavernous fistulas, 1 internal carotid aneurysm, 10 meningiomas, 16 nasopharyngeal angiofibromas, 1 post-traumatic epistaxis and 5 other vascular tumors, over the 18 months-period. Six cases of C-C fistula and ICA aneurysm were treated with the detachable balloon catheter technique. The meningiomas, angiofibromas and all other lesions were embolized with superselection of the branches of the external carotid artery such as the internal maxillary, the middle meningeal, the ascending pharyngeal the facial or other branches, using Berenstein superselective catheters or conventional angiographic catheters. The PVA (polyvinyl alcohol foam) and/or Gelfoam particles were used as embolic materials in these cases. Most of the lesions were successfully embolized with minor transient complications such as pain, headache, vomiting, fever and etc. But in 4 cases occurred the serious complications; one cerebral hemorrhage, two cerebral infarctions, and one acute laryngeal edema. The selection of the embolic materials and the catheters, and the complications are briefly discussed.

  11. Premalignant Lesions in the Kidney

    Directory of Open Access Journals (Sweden)

    Ziva Kirkali

    2001-01-01

    Full Text Available Renal cell carcinoma (RCC is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1 morphological similarity; (2 spatial association; (3 development of microinvasive carcinoma; (4 higher frequency, severity, and extent then invasive carcinoma; (5 progression to invasive cancer; and (6 similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

  12. Inhibition of hexokinase-2 with targeted liposomal 3-bromopyruvate in an ovarian tumor spheroid model of aerobic glycolysis

    Directory of Open Access Journals (Sweden)

    Gandham SK

    2015-07-01

    for both 10 µM and 25 µM concentrations. Conclusion: SKOV-3 spheroids developed by the hanging drop method can be used as a tumor aerobic glycolysis model for evaluation of therapies targeting the glycolytic pathway in cancer cells. Encapsulation of 3-BPA in a liposomal formulation improved permeability, HK2 inhibition, and cytotoxicity in the multicellular spheroid model.Keywords: ovarian cancer, aerobic glycolysis, hexokinase-2, 3-bromopyruvate, epidermal growth factor receptor-targeted liposomes

  13. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Saleha B Vuyyuri

    Full Text Available Ascorbic acid (AA exhibits significant anticancer activity at pharmacologic doses achievable by parenteral administration that have minimal effects on normal cells. Thus, AA has potential uses as a chemotherapeutic agent alone or in combination with other therapeutics that specifically target cancer-cell metabolism. We compared the effects of AA and combinations of AA with the glycolysis inhibitor 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3-PO on the viability of three non-small cell lung cancer (NSCLC cell lines to the effects on an immortalized lung epithelial cell line. AA concentrations of 0.5 to 5 mM caused a complete loss of viability in all NSCLC lines compared to a <10% loss of viability in the lung epithelial cell line. Combinations of AA and 3-PO synergistically enhanced cell death in all NSCLC cell lines at concentrations well below the IC50 concentrations for each compound alone. A synergistic interaction was not observed in combination treatments of lung epithelial cells and combination treatments that caused a complete loss of viability in NSCLC cells had modest effects on normal lung cell viability and reactive oxygen species (ROS levels. Combination treatments induced dramatically higher ROS levels compared to treatment with AA and 3-PO alone in NSCLC cells and combination-induced cell death was inhibited by addition of catalase to the medium. Analyses of DNA fragmentation, poly (ADP-ribose polymerase cleavage, annexin V-binding, and caspase activity demonstrated that AA-induced cell death is caused via the activation of apoptosis and that the combination treatments caused a synergistic induction of apoptosis. These results demonstrate the effectiveness of AA against NSCLC cells and that combinations of AA with 3-PO synergistically induce apoptosis via a ROS-dependent mechanism. These results support further evaluation of pharmacologic concentrations of AA as an adjuvant treatment for NSCLC and that combination of AA with

  14. Application of sonoelastography: Comparison of performance between mass and non-mass lesion

    International Nuclear Information System (INIS)

    Ko, Eun Sook; Choi, Hye Young; Kim, Rock Bum; Noh, Woo-Chul

    2012-01-01

    Objectives: The purpose of this study was to determine the performance of the conventional ultrasonography (US) and sonoelastography (SE) in three conditions of all lesions, confined to mass, and confined to non-mass lesion and to compare the performance of each modality between mass and non-mass lesion. Materials and methods: A total 364 patients with 375 lesions were evaluated with US and subsequently SE before performing US-guided biopsy. Two radiologists retrospectively analyzed conventional US and elasticity images by consensus. The US findings were classified as mass or non-mass lesion. With final pathology as reference, in each case of all lesions, masses, and non-mass lesions, areas under the ROC curves (Az) were calculated and compared for the two techniques. The comparison of Az values between the curves for US and SE, and between the curves for mass and non-mass lesion was performed. Results: Among 375 lesions, 104 (28%) lesions were malignant and 271 (72%) lesions were benign. 36 (9.6%) of 375 lesions were classified as non-mass lesion at US. There were statistically significant difference of performance between US and SE in cases of all lesion (p = 0.003) and mass (p = 0.023). However, there was no statistically significant difference of performance in case of non-mass lesion (p = 0.5). Comparisons of the Az values of US and SE between mass and non-mass lesions were not statistically significant (p = 0.745, p = 0.415, respectively). Conclusion: There was no statistically significant difference of performance of US and SE between mass and non-mass lesion.

  15. Prevalence of periapical lesions in endodontic treatment teeth

    Directory of Open Access Journals (Sweden)

    Juliana Machado Barroso

    2013-01-01

    Full Text Available The aim of this study was to determine the prevalence of of persistent periapical lesions after conventional endodontic therapy. The persistent periapical lesions were removed paraendodontic surgery, followed by apicoectomy. The root ends were retroprepared with ultrasound and retrofilling with MTA. The specimens were stored in formaldehyde 10%, making a total of 107 samples. The lesions were referred to the Department of Pathology, FOB-USP for microscopic analysis using the technique of serial sections. The present results showed periapical cyst (48, granuloma (43, Crohn's abscess (2, apical fibrosis (3 and others (11. . Among the lesions analyzed in this study it can be observed a higher incidence of apical periodontal cyst, followed by apical granuloma and other pathologies.

  16. PREVALENCE OF PERIAPICAL LESIONS IN ENDODONTIC TREATMENT TEETH

    Directory of Open Access Journals (Sweden)

    Francisco Carlos Ribeiro

    2013-04-01

    Full Text Available The aim of this study was to determine the prevalence of of persistent periapical lesions after conventional endodontic therapy. The persistent periapical lesions were removed paraendodontic surgery, followed by apicoectomy. The root ends were retroprepared with ultrasound and retrofilling with MTA. The specimens were stored in formaldehyde 10%, making a total of 107 samples. The lesions were referred to the Department of Pathology, FOB-USP for microscopic analysis using the technique of serial sections. The present results showed periapical cyst (48, granuloma (43, Crohn's abscess (2, apical fibrosis (3 and others (11. . Among the lesions analyzed in this study it can be observed a higher incidence of apical periodontal cyst, followed by apical granuloma and other pathologies.

  17. FFA STUDY OF MACULAR LESIONS

    Directory of Open Access Journals (Sweden)

    K. Vinayagamurthy

    2017-08-01

    Full Text Available BACKGROUND Macula is an important portion of retina that occupies the posterior pole of retina. Any disease that affects macula results in significant loss of central vision, form vision and colour vision to an extent. Macular lesions can be hereditary as well as acquired. Macular lesions occur in both younger and older individuals. Anatomically, a macular lesions can vary from a simple lesion like an RPF defect to a vision-threatening lesions like choroidal neovascular membrane. Many screening tests that are sensitive and specific are available to assess the functioning of macula called as ‘macular function test’. But, the greater understanding of the retinal vascular led to the usage of fluorescein angiogram in the detection and screening of macular, retinovascular and optic disc lesions. Through fundus fluorescein angiogram is a thirty-year-old procedure; it is still in vogue in almost all parts of the world. It has its own merits. The aim of the study is to study the role of fluorescein angiography in the evaluation of macular lesions. MATERIALS AND METHODS A hospital-based prospective randomised study was done, which included 50 patients. Detailed patient history was taken and thorough ocular and systemic examination was done. All patients were examined by ophthalmoscopy (direct and indirect and slit-lamp examination with 90D followed by fluorescein angiography. Ophthalmoscopic and fluorescein angiography findings were analysed and categorised. Patients were advised proper ocular and systemic treatment and follow up. RESULTS 50 cases with macular lesions were analysed and categorised into conditions like ARMD, CSR, macular oedema, CME, degenerations and dystrophies and miscellaneous conditions. FFA altered the diagnosis in 8% cases and categorised the cases in all cases. 16% patients developed adverse reactions like allergy, vomiting and nausea. On statistical analysis, FFA proved to be cheap and superior diagnostic tool in confirming

  18. Distribution and correlates of plantar hyperkeratotic lesions in older people

    Directory of Open Access Journals (Sweden)

    Menz Hylton B

    2009-03-01

    Full Text Available Abstract Background Plantar hyperkeratotic lesions are common in older people and are associated with pain, mobility impairment and functional limitations. However, little has been documented in relation to the frequency or distribution of these lesions. The aim of this study was to document the occurrence of plantar hyperkeratotic lesions and the patterns in which they occur in a random sample of older people. Methods A medical history questionnaire was administered to a random sample of 301 people living independently in the community (117 men, 184 women aged between 70 and 95 years (mean 77.2, SD 4.9, who also underwent a clinical assessment of foot problems, including the documentation of plantar lesion locations, toe deformities and the presence and severity of hallux valgus. Results Of the 301 participants, 180 (60% had at least one plantar hyperkeratotic lesion. Those with plantar lesions were more likely to be female (χ2 = 18.75, p 2 = 6.15, p vs 36.3 ± 8.4°; t = 2.68, df = 286, p vs 4.8 ± 1.3 hours, t = -2.46, df = 299, p = 0.01. No associations were found between the presence of plantar lesions and body mass index, obesity, foot posture, dominant foot or forefoot pain. A total of 53 different lesions patterns were observed, with the most common lesion pattern being "roll-off" hyperkeratosis on the medial aspect of the 1st metatarsophalangeal joint (MPJ, accounting for 12% of all lesion patterns. "Roll-off" lesions under the 1st MPJ and interphalangeal joint were significantly associated with moderate to severe hallux valgus (p p Conclusion Plantar hyperkeratotic lesions affect 60% of older people and are associated with female gender, hallux valgus, toe deformity, increased ankle flexibility and time spent on feet, but are not associated with obesity, limb dominance, forefoot pain or foot posture. Although there are a wide range of lesion distribution patterns, most can be classified into medial, central or lateral groups. Further

  19. Total pancreatic lipomatosis with malabsorption syndrome

    Directory of Open Access Journals (Sweden)

    Rama Anand

    2011-01-01

    Full Text Available Total fat replacement of the pancreas is rare. Focal fatty replacement is the most common degenerative lesion of pancreas. Focal fatty deposits have no major clinical significance; however, extreme fat replacement is of pathologic significance, as it is associated with marked reduction in exocrine function of pancreas, resulting in malabsorption due to pancreatic enzyme insufficiency.

  20. Fast semi-automated lesion demarcation in stroke

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    Bianca de Haan

    2015-01-01

    Full Text Available Lesion–behaviour mapping analyses require the demarcation of the brain lesion on each (usually transverse slice of the individual stroke patient's brain image. To date, this is generally thought to be most precise when done manually, which is, however, both time-consuming and potentially observer-dependent. Fully automated lesion demarcation methods have been developed to address these issues, but these are often not practicable in acute stroke research where for each patient only a single image modality is available and the available image modality differs over patients. In the current study, we evaluated a semi-automated lesion demarcation approach, the so-called Clusterize algorithm, in acute stroke patients scanned in a range of common image modalities. Our results suggest that, compared to the standard of manual lesion demarcation, the semi-automated Clusterize algorithm is capable of significantly speeding up lesion demarcation in the most commonly used image modalities, without loss of either lesion demarcation precision or lesion demarcation reproducibility. For the three investigated acute datasets (CT, DWI, T2FLAIR, containing a total of 44 patient images obtained in a regular clinical setting at patient admission, the reduction in processing time was on average 17.8 min per patient and this advantage increased with increasing lesion volume (up to 60 min per patient for the largest lesion volumes in our datasets. Additionally, our results suggest that performance of the Clusterize algorithm in a chronic dataset with 11 T1 images was comparable to its performance in the acute datasets. We thus advocate the use of the Clusterize algorithm, integrated into a simple, freely available SPM toolbox, for the precise, reliable and fast preparation of imaging data for lesion–behaviour mapping analyses.

  1. Chronic total coronary occlusion: treatment results.

    Science.gov (United States)

    Kirk Christensen, Martin; Freeman, Phillip Fischer; Rasmussen, Jeppe Groendal; Villadsen, Anton Boel; Raungaard, Bent; Eggert Jensen, Svend; Thuesen, Leif

    2017-08-01

    To describe the clinical and procedural coronary chronic total occlusion (CTO) treatment results in a Nordic PCI centre during the implementation of a CTO treatment program. In a retrospective registry study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart failure score, (3) lesion complexity and (4) adverse events during hospital stay and three months following the index procedure. The study cohort included 503 patients (594 lesions). From 2010 to 2013 96% of procedures were performed with antegrade wire-escalation technique and 4% performed using retrograde techniques, from 2013-2016 the corresponding numbers were 83% and 17.0%. The procedural success rate was 69%, increasing from 64% before to 72% (p = .06) after routinely using the retrograde approach. No individual patient characteristic, lesion variable or score was strongly associated with procedural success or failure. There were 4% serious procedure related complications. In patients with PCI of a CTO lesion only, 87% were in CCS or NYHA functional class ≥2 before the index procedure vs. 22% at follow-up. Routine use of retrograde techniques tended to increase the procedural success rate. Clinical results after three months were acceptable, but the complication rate was higher than for non-CTO PCI. Individual patient and lesion characteristics had a low predictability for procedural success. Therefore, clinical symptoms, objective signs of myocardial ischemia and procedural risk should be focus points in coronary chronic total occlusion treatment strategies.

  2. Total body photography for skin cancer screening.

    Science.gov (United States)

    Dengel, Lynn T; Petroni, Gina R; Judge, Joshua; Chen, David; Acton, Scott T; Schroen, Anneke T; Slingluff, Craig L

    2015-11-01

    Total body photography may aid in melanoma screening but is not widely applied due to time and cost. We hypothesized that a near-simultaneous automated skin photo-acquisition system would be acceptable to patients and could rapidly obtain total body images that enable visualization of pigmented skin lesions. From February to May 2009, a study of 20 volunteers was performed at the University of Virginia to test a prototype 16-camera imaging booth built by the research team and to guide development of special purpose software. For each participant, images were obtained before and after marking 10 lesions (five "easy" and five "difficult"), and images were evaluated to estimate visualization rates. Imaging logistical challenges were scored by the operator, and participant opinion was assessed by questionnaire. Average time for image capture was three minutes (range 2-5). All 55 "easy" lesions were visualized (sensitivity 100%, 90% CI 95-100%), and 54/55 "difficult" lesions were visualized (sensitivity 98%, 90% CI 92-100%). Operators and patients graded the imaging process favorably, with challenges identified regarding lighting and positioning. Rapid-acquisition automated skin photography is feasible with a low-cost system, with excellent lesion visualization and participant acceptance. These data provide a basis for employing this method in clinical melanoma screening. © 2014 The International Society of Dermatology.

  3. An anthocyanin rich strawberry extract induces apoptosis and ROS while decreases glycolysis and fibrosis in human uterine leiomyoma cells.

    Science.gov (United States)

    Islam, Md Soriful; Giampieri, Francesca; Janjusevic, Milijana; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Mazzoni, Luca; Greco, Stefania; Giannubilo, Stefano Raffaele; Ciavattini, Andrea; Mezzetti, Bruno; Capocasa, Franco; Castellucci, Mario; Battino, Maurizio; Ciarmela, Pasquapina

    2017-04-04

    Uterine leiomyomas are highly prevalent benign tumors in reproductive aged women. Unfortunately, medical treatments are still limited and no preventive therapies have been developed. In the present study, we investigated the therapeutic effects of strawberry extract on uterine leiomyoma cells. Leiomyoma and myometrial cells were treated with strawberry (cultivar Alba) extract (250 μg/ml) for 48 h to measure apoptosis, reactive oxygen species (ROS), oxidative phosphorylation (OCR, oxygen consumption rate) and glycolysis (ECAR, extracellular acidification rate) as well as fibrosis associated gene and/or protein expression. In leiomyoma cells, strawberry increased the percentage of apoptotic and dead cells. Strawberry significantly increased ROS concentration in leiomyoma cells, while decreased it in myometrial cells. After strawberry treatment, leiomyoma cells showed a significant decreased rate of ECAR, while OCR was unchanged in both myometrial and leiomyoma cells. Strawberry significantly decreased collagen1A1, fibronectin and versican mRNA expression in leiomyoma cells. The reduced protein expression of fibronectin was observed by strawberry extract in leiomyoma cells as well. Furthermore, strawberry was able to reduce activin A induced fibronectin, collagen1A1, and versican as well as activin A and PAI-1 mRNA expression in leiomyoma cells. This study suggests that strawberry can be developed as therapeutic and/or preventive agent for uterine leiomyomas.

  4. Inhibiting prenylation augments chemotherapy efficacy in renal cell carcinoma through dual inhibition on mitochondrial respiration and glycolysis.

    Science.gov (United States)

    Huang, Jiangrong; Yang, Xiaoyu; Peng, Xiaochun; Huang, Wei

    2017-11-18

    Prenylation is a posttranslational lipid modification required for the proper functions of a number of proteins involved in cell regulation. Here, we show that prenylation inhibition is important for renal cell carcinoma (RCC) growth, survival and response to chemotherapy, and its underlying mechanism may be contributed to mitochondrial dysfunction. We first demonstrated that a HMG-CoA reductase inhibitor pitavastatin inhibited mevalonate pathway and thereby prenylation in RCC cells. In addition, pitavastatin is effective in inhibiting growth and inducing apoptosis in a panel of RCC cell lines. Combination of pitavastatin and paclitaxel is significantly more effective than pitavastatin or paclitaxel alone as shown by both in vitro cell culture system and in vivo RCC xenograft model. Importantly, pitavastatin treatment inhibits mitochondrial respiration via suppressing mitochondrial complex I and II enzyme activities. Interestingly, different from mitochondrial inhibitor phenformin that inhibits mitochondrial respiration but activates glycolytic rate in RCC cells, pitavastatin significantly decreases glycolytic rate. The dual inhibitory action of pitavastatin on mitochondrial respiration and glycolysis results in remarkable energy depletion and oxidative stress in RCC cells. In addition, inhibition of prenylation by depleting Isoprenylcysteine carboxylmethyltransferase (Icmt) also mimics the inhibitory effects of pitavastatin in RCC cells. Our work demonstrates the previously unappreciated association between prenylation inhibition and energy metabolism in RCC, which can be therapeutically exploited, likely in tumors that largely rely on energy metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Engineered Trx2p industrial yeast strain protects glycolysis and fermentation proteins from oxidative carbonylation during biomass propagation

    Directory of Open Access Journals (Sweden)

    Gómez-Pastor Rocío

    2012-01-01

    Full Text Available Abstract Background In the yeast biomass production process, protein carbonylation has severe adverse effects since it diminishes biomass yield and profitability of industrial production plants. However, this significant detriment of yeast performance can be alleviated by increasing thioredoxins levels. Thioredoxins are important antioxidant defenses implicated in many functions in cells, and their primordial functions include scavenging of reactive oxygen species that produce dramatic and irreversible alterations such as protein carbonylation. Results In this work we have found several proteins specifically protected by yeast Thioredoxin 2 (Trx2p. Bidimensional electrophoresis and carbonylated protein identification from TRX-deficient and TRX-overexpressing cells revealed that glycolysis and fermentation-related proteins are specific targets of Trx2p protection. Indeed, the TRX2 overexpressing strain presented increased activity of the central carbon metabolism enzymes. Interestingly, Trx2p specifically preserved alcohol dehydrogenase I (Adh1p from carbonylation, decreased oligomer aggregates and increased its enzymatic activity. Conclusions The identified proteins suggest that the fermentative capacity detriment observed under industrial conditions in T73 wine commercial strain results from the oxidative carbonylation of specific glycolytic and fermentation enzymes. Indeed, increased thioredoxin levels enhance the performance of key fermentation enzymes such as Adh1p, which consequently increases fermentative capacity.

  6. Reactive oxygen species-driven HIF1α triggers accelerated glycolysis in endothelial cells exposed to low oxygen tension

    International Nuclear Information System (INIS)

    Paik, Jin-Young; Jung, Kyung-Ho; Lee, Jin-Hee; Park, Jin-Won; Lee, Kyung-Han

    2017-01-01

    Endothelial cells and their metabolic state regulate glucose transport into underlying tissues. Here, we show that low oxygen tension stimulates human umbilical vein endothelial cell 18 F–fluorodeoxyglucose ( 18 F–FDG) uptake and lactate production. This was accompanied by augmented hexokinase activity and membrane Glut-1, and increased accumulation of hypoxia-inducible factor-1α (HIF1α). Restoration of oxygen reversed the metabolic effect, but this was blocked by HIF1α stabilization. Hypoxia-stimulated 18 F–FDG uptake was completely abrogated by silencing of HIF1α expression or by a specific inhibitor. There was a rapid and marked increase of reactive oxygen species (ROS) by hypoxia, and ROS scavenging or NADPH oxidase inhibition completely abolished hypoxia-stimulated HIF1α and 18 F–FDG accumulation, placing ROS production upstream of HIF1α signaling. Hypoxia-stimulated HIF1α and 18 F–FDG accumulation was blocked by the protein kinase C (PKC) inhibitor, staurosporine. The phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, blocked hypoxia-stimulated 18 F–FDG uptake and attenuated hypoxia-responsive element binding of HIF1α without influencing its accumulation. Thus, ROS-driven HIF1α accumulation, along with PKC and PI3K signaling, play a key role in triggering accelerated glycolysis in endothelial cells under hypoxia, thereby contributing to 18 F–FDG transport.

  7. The Glycerate and Phosphorylated Pathways of Serine Synthesis in Plants: The Branches of Plant Glycolysis Linking Carbon and Nitrogen Metabolism.

    Science.gov (United States)

    Igamberdiev, Abir U; Kleczkowski, Leszek A

    2018-01-01

    Serine metabolism in plants has been studied mostly in relation to photorespiration where serine is formed from two molecules of glycine. However, two other pathways of serine formation operate in plants and represent the branches of glycolysis diverging at the level of 3-phosphoglyceric acid. One branch (the glycerate - serine pathway) is initiated in the cytosol and involves glycerate formation from 3-phosphoglycerate, while the other (the phosphorylated serine pathway) operates in plastids and forms phosphohydroxypyruvate as an intermediate. Serine formed in these pathways becomes a precursor of glycine, formate and glycolate accumulating in stress conditions. The pathways can be linked to GABA shunt via transamination reactions and via participation of the same reductase for both glyoxylate and succinic semialdehyde. In this review paper we present a hypothesis of the regulation of redox balance in stressed plant cells via participation of the reactions associated with glycerate and phosphorylated serine pathways. We consider these pathways as important processes linking carbon and nitrogen metabolism and maintaining cellular redox and energy levels in stress conditions.

  8. High USP6NL levels in breast cancer sustain chronic AKT phosphorylation and GLUT1 stability fueling aerobic glycolysis.

    Science.gov (United States)

    Avanzato, Daniele; Pupo, Emanuela; Ducano, Nadia; Isella, Claudio; Bertalot, Giovanni; Luise, Chiara; Pece, Salvatore; Bruna, Alejandra; Rueda, Oscar M; Caldas, Carlos; Di Fiore, Pier Paolo; Sapino, Anna; Lanzetti, Letizia

    2018-04-24

    USP6NL, also named RN-tre, is a GTPase activating protein (GAP) involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer (BC), mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in BC cells delayed endocytosis and degradation of the epidermal growth factor receptor (EGFR), causing chronic AKT activation. In turn, AKT stabilized the glucose transporter GLUT1 at the plasma membrane, increasing aerobic glycolysis. In agreement, elevated USP6NL sensitized BC cells to glucose deprivation, indicating that their glycolytic capacity relies on this protein. Depletion of USP6NL accelerated EGFR/AKT downregulation and GLUT1 degradation, impairing cell proliferation exclusively in BC cells that harbored increased levels of USP6NL. Overall, these findings argue that USP6NL overexpression generates a metabolic rewiring that is essential to foster the glycolytic demand of BC cells and promote their proliferation. Copyright ©2018, American Association for Cancer Research.

  9. Glucose Regulates Cyclin D2 Expression in Quiescent and Replicating Pancreatic β-Cells Through Glycolysis and Calcium Channels

    Science.gov (United States)

    Salpeter, Seth J.; Klochendler, Agnes; Weinberg-Corem, Noa; Porat, Shay; Granot, Zvi; Shapiro, A. M. James; Magnuson, Mark A.; Eden, Amir; Grimsby, Joseph; Glaser, Benjamin

    2011-01-01

    Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G2-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication. PMID:21521747

  10. Comparative Metabolomic Profiling Reveals That Dysregulated Glycolysis Stemming from Lack of Salvage NAD+ Biosynthesis Impairs Reproductive Development in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Wenqing; McReynolds, Melanie R; Goncalves, Jimmy F; Shu, Muya; Dhondt, Ineke; Braeckman, Bart P; Lange, Stephanie E; Kho, Kelvin; Detwiler, Ariana C; Pacella, Marisa J; Hanna-Rose, Wendy

    2015-10-23

    Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD(+) consumers to resynthesize NAD(+), resulting in a reduction in global NAD(+) bioavailability. We manipulate NAD(+) levels to demonstrate that a minor deficit in NAD(+) availability is incompatible with a normal pace of gonad development. The NAD(+) deficit compromises NAD(+) consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD(+) biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD(+) salvage biosynthesis for the purposes of inhibiting tumor growth. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Comparative Metabolomic Profiling Reveals That Dysregulated Glycolysis Stemming from Lack of Salvage NAD+ Biosynthesis Impairs Reproductive Development in Caenorhabditis elegans*

    Science.gov (United States)

    Wang, Wenqing; McReynolds, Melanie R.; Goncalves, Jimmy F.; Shu, Muya; Dhondt, Ineke; Braeckman, Bart P.; Lange, Stephanie E.; Kho, Kelvin; Detwiler, Ariana C.; Pacella, Marisa J.; Hanna-Rose, Wendy

    2015-01-01

    Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD+ consumers to resynthesize NAD+, resulting in a reduction in global NAD+ bioavailability. We manipulate NAD+ levels to demonstrate that a minor deficit in NAD+ availability is incompatible with a normal pace of gonad development. The NAD+ deficit compromises NAD+ consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD+ biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD+ salvage biosynthesis for the purposes of inhibiting tumor growth. PMID:26350462

  12. Inihibition of Glycolysis by Using a Micro/Nano-Lipid Bromopyruvic Chitosan Carrier as a Promising Tool to Improve Treatment of Hepatocellular Carcinoma

    Science.gov (United States)

    Dini, Luciana; Citti, Cinzia; Cannazza, Giuseppe

    2018-01-01

    Glucose consumption in many types of cancer cells, in particular hepatocellular carcinoma (HCC), was followed completely by over-expression of type II hexokinase (HKII). This evidence has been used in modern pharmacotherapy to discover therapeutic target against glycolysis in cancer cells. Bromopyruvate (BrPA) exhibits antagonist property against HKII and can be used to inhibit glycolysis. However, the clinical application of BrPA is mostly combined with inhibition effect for healthy cells particularly erythrocytes. Our strategy is to encapsulate BrPA in a selected vehicle, without any leakage of BrPA out of vehicle in blood stream. This structure has been constructed from chitosan embedded into oleic acid layer and then coated by dual combination of folic acid (FA) and bovine serum albumin (BSA). With FA as specific ligand for cancer folate receptor and BSA that can be an easy binding for hepatocytes, they can raise the potential selection of carrier system. PMID:29320411

  13. Inihibition of Glycolysis by Using a Micro/Nano-Lipid Bromopyruvic Chitosan Carrier as a Promising Tool to Improve Treatment of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Nemany A. Hanafy

    2018-01-01

    Full Text Available Glucose consumption in many types of cancer cells, in particular hepatocellular carcinoma (HCC, was followed completely by over-expression of type II hexokinase (HKII. This evidence has been used in modern pharmacotherapy to discover therapeutic target against glycolysis in cancer cells. Bromopyruvate (BrPA exhibits antagonist property against HKII and can be used to inhibit glycolysis. However, the clinical application of BrPA is mostly combined with inhibition effect for healthy cells particularly erythrocytes. Our strategy is to encapsulate BrPA in a selected vehicle, without any leakage of BrPA out of vehicle in blood stream. This structure has been constructed from chitosan embedded into oleic acid layer and then coated by dual combination of folic acid (FA and bovine serum albumin (BSA. With FA as specific ligand for cancer folate receptor and BSA that can be an easy binding for hepatocytes, they can raise the potential selection of carrier system.

  14. Workflow-centred evaluation of an automatic lesion tracking software for chemotherapy monitoring by CT

    Energy Technology Data Exchange (ETDEWEB)

    Moltz, Jan Hendrik; Peitgen, Heinz-Otto [Fraunhofer MEVIS - Institute for Medical Image Computing, Bremen (Germany); D' Anastasi, Melvin [University Hospital Munich-Grosshadern, Department of Clinical Radiology, Muenchen (Germany); Kiessling, Andreas [University Hospital Giessen and Marburg, Department of Diagnostic Radiology, Marburg (Germany); Pinto dos Santos, Daniel [University Hospital Mainz, Department of Diagnostic and Interventional Radiology, Mainz (Germany); Schuelke, Christoph [University Hospital Muenster, Institute of Clinical Radiology, Muenster (Germany)

    2012-12-15

    In chemotherapy monitoring, an estimation of the change in tumour size is an important criterion for the assessment of treatment success. This requires a comparison between corresponding lesions in the baseline and follow-up computed tomography (CT) examinations. We evaluate the clinical benefits of an automatic lesion tracking tool that identifies the target lesions in the follow-up CT study and pre-computes the lesion volumes. Four radiologists performed volumetric follow-up examinations for 52 patients with and without lesion tracking. In total, 139 lung nodules, liver metastases and lymph nodes were given as target lesions. We measured reading time, inter-reader variability in lesion identification and volume measurements, and the amount of manual adjustments of the segmentation results. With lesion tracking, target lesion assessment time decreased by 38 % or 22 s per lesion. Relative volume difference between readers was reduced from 0.171 to 0.1. Segmentation quality was comparable with and without lesion tracking. Our automatic lesion tracking tool can make interpretation of follow-up CT examinations quicker and provide results that are less reader-dependent. (orig.)

  15. Squamous intraepithelial lesions of the anal squamocolumnar junction: Histopathological classification and HPV genotyping

    Directory of Open Access Journals (Sweden)

    Omar Clavero

    2017-06-01

    Full Text Available Background: Human papillomavirus (HPV-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ. We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and –positive patients. Methods: Histopathology identified 47 squamous intraepithelial lesions (SILs adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping. Results: Sixteen (16/47 of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47 were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM; Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6. Conclusions: Clinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative. Keywords: Anal squamocolumnar junction, Low-grade squamous intraepithelial lesion (LSIL, High-grade squamous intraepithelial lesion (HSIL, Papillary immature metaplasia (PIM, HPV, HIV

  16. MRI of the stener lesion

    International Nuclear Information System (INIS)

    Haramati, N.; Hiller, N.; Dowdle, J.; Jacobson, M.; Barax, C.N.; Lieberfarb, R.I.; Lester, B.; Kulick, R.G.

    1995-01-01

    Six cadaver thumbs had ulnar collateral ligament (UCL) tears created surgically. MR examinations (2D STIR and 3D GRASS) were performed identically on all specimens both before displacement (non-Stener) and after displacement (Stener lesion) of the UCL. The MR images were then randomly numbered. Each image was evaluated separately in blinded fashion by four musculoskeletal radiologists for the presence or absence of a Stener lesion. Each radiologist reinterpreted the images after an interval of several days. The interpretation was based on previously published criteria for Stener lesion diagnosis by MR. The sensitivity of GRASS ranged from 0.17 to 0.67 with the most experienced reader scoring the lowest. The specificity of GRASS ranged from 0.33 to 1.0 (most experienced reader 0.67, 0.83). STIR had a sensitivity of 0.00-0.17 and a specificity of 0.53-0.83. The K values for inter- and intraobserver agreement were measured. The intraobserver K for GRASS was 0.27-0.75 (most experienced reader 0.75). 2D imaging is probably inadequate for the evaluation of Stener lesions. The most likely reason is that the STIR slice thickness of 3 mm limits resolution of small UCLs. The poor sensitivity and specificity of GRASS as well as poor interobserver agreement suggest that MR may not be sufficiently accurate for Stener lesion evaluation. (orig./MG)

  17. Real-Time DNP NMR Observations of Acetic Acid Uptake, Intracellular Acidification, and of Consequences for Glycolysis and Alcoholic Fermentation in Yeast

    DEFF Research Database (Denmark)

    Jensen, Pernille Rose; Karlsson, Magnus; Lerche, Mathilde Hauge

    2013-01-01

    Uptake and upshot in vivo: Straightforward methods that permit the real-time observation of organic acid influx, intracellular acidification, and concomitant effects on cellular-reaction networks are crucial for improved bioprocess monitoring and control (see scheme). Herein, dynamic nuclear pola...... polarization (DNP) NMR is used to observe acetate influx, ensuing intracellular acidification and the metabolic consequences on alcoholic fermentation and glycolysis in living cells....

  18. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as non-invasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    Science.gov (United States)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H. Douglas; Munasinghe, Jeeva P.; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P.; Mitchell, James B.; Krishna, Murali C.

    2012-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation, and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate (3-BP) blocks glycolysis pathway by inhibiting hypoxia inducible enzymes, and enhanced cytotoxicity of 3-BP under hypoxic conditions has been reported in vitro. However, the efficacy of 3-BP was substantially attenuated in hypoxic tumor regions (pO2 < 10 mmHg) in vivo using squamous cell carcinoma (SCCVII)-bearing mouse model. Metabolic MRI studies using hyperpolarized 13C-labeled pyruvate showed that monocarboxylate transporter-1 (MCT1) is the major transporter for pyruvate and the analog 3-BP in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of MCT1 in vivo. Expression of MCT1 was enhanced in moderately hypoxic (8–15 mmHg) tumor regions, but down regulated in severely hypoxic (< 5 mmHg) tumor regions. These results emphasize the importance of non-invasive imaging biomarkers to confirm the action of hypoxia-activated drugs. PMID:22692861

  19. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate.

    Science.gov (United States)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H Douglas; Munasinghe, Jeeva P; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P; Mitchell, James B; Krishna, Murali C

    2013-05-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under hypoxic conditions has been reported in vitro. However, the efficacy of 3-bromopyruvate was substantially attenuated in hypoxic tumor regions (pO23-bromopyruvate in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of monocarboxylate transporter-1 in vivo. Expression of monocarboxylate transporter-1 was enhanced in moderately hypoxic (8-15 mmHg) tumor regions but down regulated in severely hypoxic (<5 mmHg) tumor regions. These results emphasize the importance of noninvasive imaging biomarkers to confirm the action of hypoxia-activated drugs. Copyright © 2012 Wiley Periodicals, Inc.

  20. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    Science.gov (United States)

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

  1. Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis.

    Science.gov (United States)

    Hyder, Fahmeed; Herman, Peter; Bailey, Christopher J; Møller, Arne; Globinsky, Ronen; Fulbright, Robert K; Rothman, Douglas L; Gjedde, Albert

    2016-05-01

    Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with (31)P and (13)C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements. © The Author(s) 2016.

  2. Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-13C2 glucose

    Science.gov (United States)

    Jalloh, Ibrahim; Carpenter, Keri L H; Grice, Peter; Howe, Duncan J; Mason, Andrew; Gallagher, Clare N; Helmy, Adel; Murphy, Michael P; Menon, David K; Carpenter, T Adrian; Pickard, John D; Hutchinson, Peter J

    2015-01-01

    Increased ‘anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-13C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. 13C enrichment for glycolytic 2,3-13C2 lactate was the median 5.4% (interquartile range (IQR) 4.6–7.5%) in TBI brain and 4.2% (2.4–4.4%) in ‘normal' brain (Pbrain and 6.7% (6.3–8.9%) in ‘normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=−0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than ‘normal' brain. Several TBI patients exhibited PPP–lactate elevation above the ‘normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain. PMID:25335801

  3. Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

    Science.gov (United States)

    Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

    2017-09-16

    Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Abfraction lesions reviewed: current concepts

    Directory of Open Access Journals (Sweden)

    Adriana de Fátima Vasconcelos Pereira

    2008-01-01

    Full Text Available Non-carious cervical lesions are characterized by structural loss near the cementoenamel junction, without the presence of caries. Anumber of theories have arisen to explain the etiology of such lesions, although the real causes remain obscure, as is reflected by the contradictory terminology used in the literature. In addition to describing acidic and abrasive processes documented as etiological factors, attention is given to the role of mechanical stress from occlusal load, which is the most accepted theory for the development of abfraction lesions. Considering that tensile stress leads to the failure of restorations in the cervical region and that this is a fruitful area for future research, the present study has highlighted diagnosis, prognosis and the criteria for treatment.

  5. Ultrasonography of chest wall lesion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Cheol Min; Kim, C. H.; Cha, I. H.; Chung, K. B.; Ser, W. H.; Choi, Y. H. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    Thirty-one patients with chest wall diseases were studied with ultrasound to evaluate its role in chest wall lesions. There were eight infectious conditions, 9 benign tumors, 11 malignant lesions and 3 miscellaneous cases. Diffuse chest wall thickening with heterogeneous echogenicity and obliteration of subcutaneous fat layer are findings of acute infection. In cases of tuberculous smpyema necessitates, pleural abnormality extended to the chest wall through intercostal space. Benign tumors were well demarcated, except in 4 cases of lipoma/lipomatosis. Malignant lesions showed irregular soft tissue masses, bone destruction, pleural effusion and subcutaneous invasion. Multiple enlarged lymph nodes were also shown. Ultrasound can demonstrate te internal structure, extent, depth and associated findings such as pleural effusion, bone destruction and peripheral lung involvement. Ultrasound is not only safe, non-invasive and an effective diagnostic imaging modality for chest wall disease, but can also guide aspiration or biopsy for pathologic diagnosis

  6. Ultrasonography of chest wall lesion

    International Nuclear Information System (INIS)

    Park, Cheol Min; Kim, C. H.; Cha, I. H.; Chung, K. B.; Ser, W. H.; Choi, Y. H.

    1989-01-01

    Thirty-one patients with chest wall diseases were studied with ultrasound to evaluate its role in chest wall lesions. There were eight infectious conditions, 9 benign tumors, 11 malignant lesions and 3 miscellaneous cases. Diffuse chest wall thickening with heterogeneous echogenicity and obliteration of subcutaneous fat layer are findings of acute infection. In cases of tuberculous smpyema necessitates, pleural abnormality extended to the chest wall through intercostal space. Benign tumors were well demarcated, except in 4 cases of lipoma/lipomatosis. Malignant lesions showed irregular soft tissue masses, bone destruction, pleural effusion and subcutaneous invasion. Multiple enlarged lymph nodes were also shown. Ultrasound can demonstrate te internal structure, extent, depth and associated findings such as pleural effusion, bone destruction and peripheral lung involvement. Ultrasound is not only safe, non-invasive and an effective diagnostic imaging modality for chest wall disease, but can also guide aspiration or biopsy for pathologic diagnosis

  7. The radiology in the solitary bone lesions

    International Nuclear Information System (INIS)

    Veloso, G.A.; Cardoso, V.M.

    1985-01-01

    Three methods of radiologic analysis of the solitary bone lesions are reviewed. 1. Radiological analysis of the lesions with the objective to suppose the histologic type; 2. To appreciate the velocity of growth and aggressiveness of the lesions. 3. To appreciate the biological behaviour of the bone lesions, making the diagnosis necessary for the treatment. (M.A.C.) [pt

  8. [The treatment of decubitus lesions].

    Science.gov (United States)

    Fugazza, G; Moroni, S; Bona, F

    1995-01-01

    The authors present a plan for pharmacological treatment of pressure sores in patients affected by neurological pathologies: cerebrovascular accidents, head injuries, spinal cord injuries. This plan is easily applicable to all pressure sores included between first and third degree of the Reuler and Cooney classification. Authors identified some drugs specifically usefull in different cutaneous lesion degrees. Skin lesions and employed medicines are described as follows: Erythema: semi occlusive bandage with porous adsorbing membrane. This dressing must be left in for five days at least. Excoriation: bactericidal or bacteriostatic medicines if it's situated in a non pressed area while the same dressing utilized for erythema if it's localized in a pressed area. Pressure sores: if there is local infection cleanse the wound from bacterial defilement using topic antibiotics apply compresses with vitamin C if the cutaneous lesion is larger than deeper, Cadexomero lodico if it's deeper than larger. Fistulas: wadding with tablets of collagen. Necrobiosis: complete or partial surgical removal of eschar preceded by the use of enzymatic drugs when eschar is firmly adherent to subcutaneous tissues. The first group collects 9 patients with stroke and head injury: 8 with sacral and 1 with heel pressure sores. First degree pressure sores heal within 45 days and third degree lesions within 160 days. The second group collects 10 spinal cord injury patients mostly with complete lesion among which: 7 sacral, 1 heel, 1 ischiatic and 1 malleolar lesions. First degree pressure sores heal within 30 days, third degree pressure sores heal within 200 days. Healing time are considered acceptable. Pressure sores recovery swiftness can be related to different factors such as pressure sores sterness, neurological pathology and arising of clinical complication (hyperthermia, infections, low serum albumin values, etc).

  9. Lesions of juxtacortical origin (surface lesions of bone)

    International Nuclear Information System (INIS)

    Kenan, S.; Abdelwahab, I.F.; Klein, M.J.; Hermann, G.; Lewis, M.M.

    1993-01-01

    A large variety of tumor and tumor-like conditions have been shown to originate from the surface of bone. Most surface lesions are associated with periosteal reaction. The periosteum is a multipotential membrane. Its cellular composition may give rise to a variety of both neoplasms and tumor-like conditions. To avoid misinterpretation, the orthopedist, radiologist, and pathologist should be familiar with the entire spectrum of surface lesions. A better understanding of the natural history and biological behavior at different lesional maturity stages and correlation of the history with the radiographic and pathological findings is essential to establish the correct diagnosis. A history of injury of blunt trauma is very important. A stress fracture may produce a periosteal reaction acd callus that can be difficult to distinguish from osteosarcoma. In this review article, the authors wish to describe and define each term by its anatomy and radiographic features while discussing the entire spectrum of surface lesions. All the illustrative cases in this review article have been proven histologically. (orig.)

  10. Periapical lesions: diagnosis and treatment

    OpenAIRE

    García-Rubio, A.; Bujaldón-Daza, A.L.; Rodríguez-Archilla, A.

    2015-01-01

    Las lesiones periapicales resultado de la necrosis de la pulpa dental son las patologías que más frecuentemente ocurren encontradas en el hueso alveolar. El tratamiento consiste en la eliminación de los agentes infecciosos mediante el tratamiento del canal radicular, permitiendo la cicatrización de la lesión. Periapical lesions, which are a result of the necrosis of the dental pulp, are the most frequently occurring diseases found in the alveolar bone. The treatment involves the removal of...

  11. Localized lesions in secondary syphillis

    International Nuclear Information System (INIS)

    Rasid, N.; Syphilis, S.

    2008-01-01

    The clinical manifestations of secondary syphilis are variable and can mimic many skin diseases, mostly being generalized and symmetrical in distribution. Localized lesions of secondary syphilis are rarely seen in dermatology clinics. We report an unusual presentation wherein a patient had localized lesions over face and soles only. There is a need for increased awareness on the part of physicians to recognize new patterns of syphilitic infection, together with a willingness to consider the diagnosis of syphilis in patients with unusual clinical features. (author)

  12. Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

    Science.gov (United States)

    Li, L M; Cendes, F; Watson, C; Andermann, F; Fish, D R; Dubeau, F; Free, S; Olivier, A; Harkness, W; Thomas, D G; Duncan, J S; Sander, J W; Shorvon, S D; Cook, M J; Arnold, D L

    1997-02-01

    Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

  13. The Impact of Quantitative Data Provided by a Multi-spectral Digital Skin Lesion Analysis Device on Dermatologists'Decisions to Biopsy Pigmented Lesions.

    Science.gov (United States)

    Farberg, Aaron S; Winkelmann, Richard R; Tucker, Natalie; White, Richard; Rigel, Darrell S

    2017-09-01

    BACKGROUND: Early diagnosis of melanoma is critical to survival. New technologies, such as a multi-spectral digital skin lesion analysis (MSDSLA) device [MelaFind, STRATA Skin Sciences, Horsham, Pennsylvania] may be useful to enhance clinician evaluation of concerning pigmented skin lesions. Previous studies evaluated the effect of only the binary output. OBJECTIVE: The objective of this study was to determine how decisions dermatologists make regarding pigmented lesion biopsies are impacted by providing both the underlying classifier score (CS) and associated probability risk provided by multi-spectral digital skin lesion analysis. This outcome was also compared against the improvement reported with the provision of only the binary output. METHODS: Dermatologists attending an educational conference evaluated 50 pigmented lesions (25 melanomas and 25 benign lesions). Participants were asked if they would biopsy the lesion based on clinical images, and were asked this question again after being shown multi-spectral digital skin lesion analysis data that included the probability graphs and classifier score. RESULTS: Data were analyzed from a total of 160 United States board-certified dermatologists. Biopsy sensitivity for melanoma improved from 76 percent following clinical evaluation to 92 percent after quantitative multi-spectral digital skin lesion analysis information was provided ( p quantitative data were provided. Negative predictive value also increased (68% vs. 91%, panalysis (64% vs. 86%, p data into physician evaluation of pigmented lesions led to both increased sensitivity and specificity, thereby resulting in more accurate biopsy decisions.

  14. Disseminated paracoccidioidomycosis diagnosis based on oral lesions

    Directory of Open Access Journals (Sweden)

    Liana Preto Webber

    2014-01-01

    Full Text Available Paracoccidioidomycosis (PCM is a deep mycosis with primary lung manifestations that may present cutaneous and oral lesions. Oral lesions mimic other infectious diseases or even squamous cell carcinoma, clinically and microscopically. Sometimes, the dentist is the first to detect the disease, because lung lesions are asymptomatic, or even misdiagnosed. An unusual case of PCM with 5 months of evolution presenting pulmonary, oral, and cutaneous lesions that was diagnosed by the dentist based on oral lesions is presented and discussed.

  15. Multivariate analysis of magnetic resonance imaging of focal hepatic lesions

    International Nuclear Information System (INIS)

    Fujishima, Mamoru; Suemitsu, Ichizou; Sei, Tetsurou; Takeda, Yoshihiro; Hiraki, Yoshio

    1993-01-01

    A total of 124 lesions from 1 to 6 cm in diameter, including 31 cavernous hemangiomas, 32 metastases and 61 hepatocellular carcinomas (HCC) were analyzed to study the usefulness of magnetic resonance imaging (MRI) at 0.5 Tesla to differentiate focal hepatic lesions on the basis of qualitative criteria. Each focal hepatic lesion was assessed for shape, internal architecture and signal intensity relative to normal liver parenchyma. While all cavernous hemangiomas and metastases except one lesion could be detected, detection rate of HCC was significantly inferior to that of the other two diseases. A tumor capsule and a hyperintense focus on T 1 -weighted images were demonstrated in only HCC lesions in strong contrast with the other two diseases; however, metastases with slow-growing characteristics or subacute hematoma may appear as similar images. Cavernous hemangiomas appeared markedly hyperintense on T 2 -weighted images in 23 of 31 lesions, but one metastasis and one HCC had similar images. A multivariate analysis of several MRI resulted in the following mean discriminant scores: cavernous hemangioma, -1.2652; metastasis, 0.1830; and HCC, 0.7138. It appeared to be possible to differentiate the three diseases with 84.4 percent accuracy. (author)

  16. Correlation of the SLAP lesion with lesions of the medial sheath of the biceps tendon and intra-articular subscapularis tendon

    Directory of Open Access Journals (Sweden)

    Bennett William

    2009-01-01

    Full Text Available Background: Superior labral anterior to posterior (SLAP lesions have been well described in the literature and are thought to be secondary to traction injuries to the biceps anchor and/or falls on the outstretched arm. The pulley has recently been described as a structure that aids in the prevention of biceps instability. The intra-articular subscapularis insertion (IASS has been noted to contribute to the robust nature of the medial sheath. The purpose of the study was to determine a potential correlation of SLAP lesions and pulley lesions with/without IASS lesions, (hereafter referred to as medial sheath as forces that can disrupt the biceps anchor and may also disrupt structures of the medial sheath or vice-versa. Materials and Methods: Three hundred and sixteen consecutive shoulder arthroscopies performed by one surgeon were reviewed retrospectively. Operative reports and arthroscopic pictures were carefully reviewed with particular attention paid to the labral and pulley pathology. Selection bias was noted as the author had never operated primarily for a Type 1 SLAP lesion. Following, however, and as such, the exclusion criteria, was a Type 1 SLAP. Results: There were a total of 30 SLAP lesions and a total of 126 medial sheath lesions. There were 13 patients who had both SLAP and medial sheath lesions. There were 17 patients who had a SLAP lesion without a medial sheath lesion. There were 96 medial sheath lesions without a SLAP. A comparison of rates between patients who had a medial sheath lesion with a SLAP and those who had a medial sheath lesion without a SLAP, for the 316 patients, and when tested with a Fisher exact test revealed that there was no statistical significance, P = 0.673. The prevalence of SLAP lesions in this population of 316 patients was 9.4%, Buford 1%, medial sheath lesions 39%, and SLAP and medial sheath lesions 4%. Interestingly, there were three Buford complexes, all associated with a SLAP and one Buford complex

  17. Impact of variations in fatty liver on sonographic detection of focal hepatic lesions originally identified by CT

    OpenAIRE

    Wu, Size; Tu, Rong; Nan, Ruixia; Liu, Guangqing; Cui, Xiaojing; Liang, Xian

    2015-01-01

    Purpose: The aim of this study was to investigate the influence of variations in fatty liver on the ultrasonographic detection of focal liver lesions. Methods: A total of 229 patients with varying degrees of fatty liver and focal liver lesions and 200 patients with focal liver lesions but no fatty liver were randomly selected for inclusion in groups I and II, respectively. Findings of focal liver lesions identified on computed tomography were taken as the reference, and findings on ultrasonog...

  18. Imaging inflammatory acne: lesion detection and tracking

    Science.gov (United States)

    Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

    2010-02-01

    It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

  19. Quantification and Localization of Mast Cells in Periapical Lesions

    African Journals Online (AJOL)

    and Oral Biology, Basic Dental. Sciences, Faculty of ... vessels and are especially prominent near skin, mucosa of the lungs, and ... population and growth factors associated with maintenance ... Materials and Methods: A total of 30 cases and out of which ... diseases, including periapical lesions, inflammatory reactions.

  20. Cystic Lesions in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Macarena Gompertz

    2015-11-01

    Full Text Available Autoimmune pancreatitis (AIP can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  1. Stereotactic lesioning for mental illness

    International Nuclear Information System (INIS)

    Kim, M.-C.; Lee, T.-K.

    2008-01-01

    The authors report stereotactically created lesioning by radiofrequency or Cyberknife radiosurgery for patients with mental illness. Since 1993, thirty-eight patients have undergone stereotactic psychosurgery for medically intractable mental illnesses. Two patients had aggressive behavior. Twenty-five patients suffered from Obsessive-Compulsive Disorder (OCD) and ten patients had depression. Another patient suffered from atypical psychosis. Bilateral amygdalotomy and subcaudate tractotomy were done for aggressive behavior. Limbic leucotomy or anterior cingulotomy was done for CCD and subcaudate tractotomy with or without cingulotomy was done for depression. In twenty-three patients, the lesions were made by a radiofrequency (RF) lesion generator. In fifteen cases, the lesions were made with Cyberknife Radiosurgery (CKRS). The Overt Aggression Scale (OAS) declined from 8 to 2 with clinical improvement during follow up period. With long-term follow up (meaning 57 months) in 25 OCDs, the mean Yale Brown Obsessive Compulsive Score (YBOCS) declined from 34 to 13 (n = 25). The Hamilton Depression scale (HAMD) for ten patients with depression declined from 38.5 to 10.5 (n = 10). There was no operative mortality and no significant morbidity except one case with transient urinary incontinence. Authors suggest that stereotactic psychosurgery by RF and CKRS could be a safe and effective means of treating some medically intractable mental illnesses. (author)

  2. Secondary syphilis lesions resembling pityriasis

    International Nuclear Information System (INIS)

    Dar, N.R.; Ali, L.; Nawaz, M.A.

    2007-01-01

    This case report describes a male patient who presented with generalized, centrally-ulcerated papules with crusts and hypopigmented macules. Initially, differential diagnostic considerations included pityriasis lichenoides but the serology for syphilis was positive and there was a rapid response to penicillin with clearing of the lesions at the end of three weeks treatment. (author)

  3. Oral white lesion-histomorhological assessment and associated risk factor

    International Nuclear Information System (INIS)

    Orakzai, G.; Nisa, W.U.; Orakzai, S.H.

    2015-01-01

    Oral white lesions constitute a major clinical problem in Pakistan and South Asian countries. The study was done with the objective to analyse oral white lesions histologically and clinically, and evaluate association between various risk factors in different ages, gender, ethnic groups, sites and sizes of the lesion. Methods: A total of 80 patients presenting with oral white lesions were included in this cross-sectional study conducted at Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi. The biopsy sample was fixed in 10% formalin and after standardized processing, slides were prepared, stained by Hematoxylin and Eosin, with special stains when required. The histo-pathological diagnosis of lesion was recorded. Mean and standard deviation were calculated for quantitative variable. Frequency and percentages were calculated for qualitative variables. Results: Out of total 80 patients 43 were females and 37 males. The mean age of cases was 47.92 years. Majority of the patients were between 30-39 years. Buccal mucosa was affected in majority of the cases (55%), followed by lateral border of tongue 17.5% and lip mucosa (8.8%). No risk factor had been observed in almost half of the patients. Histologically Lichen Planus was the most common lesion (32.5%), followed by chronic nonspecific inflammation in (22.5%), keratosis without dysplasia (10%), keratosis with dysplasia (8.8%), Pemphigus vulgaris (7.5%), fungal infestation (5%) and Squamous cell carcinoma (3.8%). Conclusion: Oral Lichen Planus was the most common oral white lesion in our set up, with buccal mucosa involved in majority of the cases. Association between histo-pathological diagnosis with age and gender was insignificant. However, significant association was observed between histopathological diagnosis and site. Among risk factors significant association was seen between snuff dippers and pan users. (author)

  4. Defective glycolysis and the use of 2-deoxy-D-glucose in polycystic kidney disease: from animal models to humans.

    Science.gov (United States)

    Magistroni, Riccardo; Boletta, Alessandra

    2017-08-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies. Several of these potential treatments have proved effective in slowing down disease progression in pre-clinical animal studies, while only one has subsequently been proven to effectively slow down disease progression in patients, and it has recently been approved for therapy in Europe, Canada and Japan. Among the affected cellular functions and pathways, recent investigations have described metabolic derangement in ADPKD as a major trait offering additional opportunities for targeted therapies. In particular, increased aerobic glycolysis (the Warburg effect) has been described as a prominent feature of ADPKD kidneys and its inhibition using the glucose analogue 2-deoxy-D-glucose (2DG) proved effective in slowing down disease progression in preclinical models of the disease. At the same time, previous clinical experiences have been reported with 2DG, showing that this compound is well tolerated in humans with minimal and reversible side effects. In this work, we review the literature and speculate that 2DG could be a good candidate for a clinical trial in humans affected by ADPKD.

  5. Overexpression of miR-206 suppresses glycolysis, proliferation and migration in breast cancer cells via PFKFB3 targeting

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Xin; Lyu, Pengwei; Cao, Zhang; Li, Jingruo; Guo, Guangcheng; Xia, Wanjun; Gu, Yuanting, E-mail: zzyuantinggu@126.com

    2015-08-07

    miRNAs, sorting as non-coding RNAs, are differentially expressed in breast tumor and act as tumor promoters or suppressors. miR-206 could suppress the progression of breast cancer, the mechanism of which remains unclear. The study here was aimed to investigate the effect of miR-206 on human breast cancers. We found that miR-206 was down-regulated while one of its predicted targets, 6-Phosphofructo-2-kinase (PFKFB3) was up-regulated in human breast carcinomas. 17β-estradiol dose-dependently decreased miR-206 expression as well as enhanced PFKFB3 mRNA and protein expression in estrogen receptor α (ERα) positive breast cancer cells. Furthermore, we identified that miR-206 directly interacted with 3′-untranslated region (UTR) of PFKFB3 mRNA. miR-206 modulated PFKFB3 expression in MCF-7, T47D and SUM159 cells, which was influenced by 17β-estradiol depending on ERα expression. In addition, miR-206 overexpression impeded fructose-2,6-bisphosphate (F2,6BP) production, diminished lactate generation and reduced cell proliferation and migration in breast cancer cells. In conclusion, our study demonstrated that miR-206 regulated PFKFB3 expression in breast cancer cells, thereby stunting glycolysis, cell proliferation and migration. - Highlights: • miR-206 was down-regulated and PFKFB3 was up-regulated in human breast carcinomas. • 17β-estradiol regulated miR-206 and PFKFB3 expression in ERα+ cancer cells. • miR-206directly interacted with 3′-UTR of PFKFB3 mRNA. • miR-206 fructose-2,6-bisphosphate (F2,6BP) impeded production and lactate generation. • miR-206 reduced cell proliferation and migration in breast cancer cells.

  6. Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

    Science.gov (United States)

    Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James; Svanborg, Catharina

    2014-01-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic and metabolomic technology we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted the sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, the HAMLET sensitivity was modified by the glycolytic state of the tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen Hexokinase 1, PFKFB1 and HIF1α modified HAMLET sensitivity. Hexokinase 1 was shown to bind HAMLET in a protein array containing approximately 8000 targets and Hexokinase activity decreased within 15 minutes of HAMLET treatment, prior to morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. The glycolytic machinery was modified and glycolysis was shifted towards the pentose phosphate pathway. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 minutes. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene-addiction or the Warburg effect. PMID:21643007

  7. The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity.

    Science.gov (United States)

    Mazzio, Elizabeth; Soliman, Karam F A

    2003-01-01

    concluded from these studies that several metabolic intermediates are effective in fueling anaerobic glycolysis during mitochondrial inhibition by MPP+.

  8. DIAGNOSTIC UTILITY OF USG-GUIDED FNAC IN HEPATIC LESIONS

    Directory of Open Access Journals (Sweden)

    Sudha P. Meena

    2016-06-01

    Full Text Available INTRODUCTION Guided fine-needle aspiration cytology (FNAC is an easy, rapid, minimally invasive and a cost effective diagnostic method for detecting benign and malignant lesions of liver. AIM The main aim of the present study was to establish the incidence of various hepatic lesions and to find out adequacy and utility of the procedure. MATERIAL AND METHOD A total of 174 cases were included in the study from Government Medical College, Kota and associated hospitals. All cases diagnosed to have single or multiple hepatic mass lesions on USG were included in the study. RESULTS Most common age group affected by hepatic lesion was 51-60 years (34.0%. 91.4% cases were having adequate aspirates. 95.6% of the total diagnosed cases were malignant and among malignant cases majority were metastatic. CONCLUSION USG-guided FNAC is a very useful procedure in the diagnosis of hepatic lesions as the procedure is simple and safe. Thus, FNAC is a simple and effective diagnostic tool in our hand.

  9. A comparative evaluation of Imaging Efficiency for elevated lesions of gallbladder

    International Nuclear Information System (INIS)

    Shizuma, Toru; Karasawa, Eii; Azuma, Tsukasa; Takasaki, Ken; Hayashi, Naoaki

    1999-01-01

    Imaging Efficiency was analyzed in 118 cases of benign lesion, including adenoma and 36 cases of malignant lesion without lymph node metastasis (Stage I) of 154 cases histologically diagnosed as elevated lesions of the gallbladder (443 lesions). On ultrasonography, the maximum diameter of the benign lesions, except in the case of adenomyomatosis, was 17 mm; the minimum diameter in the case of adenocarcinoma was 7 mm. The frequency of malignancy among elevated mucosal lesions of gallbladder with a diameter of 13 to 16 mm, except in the case of adenomyomatosis was 42.1% (8/19 lesions). Of the 91 out of total 154 cases in which the elevated lesions were 10 mm or smaller in a diameter, malignant cases were observed in 5.5% (5/91 cases). Many of the malignant lesions had a solid pattern of internal echo and there was a significant difference in depiction rate on plain CT between benign and malignant lesions. We conclude that plan CT examination is helpful to differentiate benign from malignant lesions of the gallbladder. (author)

  10. Betel quid oral lichenoid lesions: a hospital based cross-sectional study.

    Science.gov (United States)

    Arya, Sugandha; Vengal, Manoj; Raju, Bina; Patil, Neelkant; Sathosker, Sujatha; Bateja, Sumit; David, Jamil

    2017-02-01

    The aim of this study was to assess the prevalence and risk indicators of betel quid oral lichenoid lesions in chewers. A total of 1209 chewers were identified and categorized into three main groups based on the type of lesion: betel quid oral lichenoid lesions only, betel quid oral lichenoid lesions in association with quid-induced other oral mucosal lesions, and no lesions. Multinomial regression analyses were used to determine associations between dependent and independent variables. Betel quid oral lichenoid lesions were more common in individuals who chewed quid comprising both tobacco and areca nut, and in those who chewed it two to three, or greater than three, times a day. Betel quid oral lichenoid lesions + quid-induced other oral mucosal lesions were more likely to occur in females, and in individuals who chewed quid containing both tobacco and areca nut, in their processed and unprocessed forms, and greater than three times a day. The prevalence of betel quid oral lichenoid lesions was higher than that reported in previous studies conducted in India. Increase in the frequency and duration of quid chewing was associated with increased likelihood of developing these oral lichenoid lesions. © 2015 Wiley Publishing Asia Pty Ltd.

  11. Breast vibro-acoustography: initial experience in benign lesions

    International Nuclear Information System (INIS)

    Alizad, Azra; Mehrmohammadi, Mohammad; Ghosh, Karthik; Glazebrook, Katrina N; Carter, Rickey E; Karaberkmez, Leman Gunbery; Whaley, Dana H; Fatemi, Mostafa

    2014-01-01

    Vibro-acoustography (VA) is a newly developed imaging technology that is based on low-frequency vibrations induced in the object by the radiation force of ultrasound. VA is sensitive to the dynamic characteristics of tissue. Here, we evaluate the performance of VA in identifying benign lesions and compare the results to those of mammography. An integrated mammography-VA system designed for in vivo breast imaging was tested on a group of female volunteers, age ≥ 18 years, with suspected breast lesions based on clinical examination. A set of VA scans was acquired after each corresponding mammography. Most lesions were classified as benign based on their histological results. However, in 4 cases, initial diagnosis based on clinical imaging determined that the lesions were cysts. These cysts were aspirated with needle aspiration and disappeared completely under direct ultrasound visualization. Therefore, no biopsies were performed on these cases and lesions were classified as benign based on clinical findings per clinical standards. To define the VA characteristics of benign breast masses, we adopted the features that are normally attributed to such masses in mammography. In a blinded assessment, three radiologists evaluated the VA images independently. The diagnostic accuracy of VA for detection of benign lesions was assessed by comparing the reviewers’ evaluations with clinical data. Out of a total 29 benign lesions in the group, the reviewers were able to locate all lesions on VA images and mammography, 100% with (95% confidence interval (CI): 88% to 100%). Two reviewers were also able to correctly classify 83% (95% CI: 65% to 92%), and the third reviewer 86% (95% CI: 65% to 95%) of lesions, as benign on VA images and 86% (95% CI: 69% to 95%) on mammography. The results suggest that the mammographic characteristics of benign lesion may also be used to identify such lesions in VA. Furthermore, the results show the ability of VA to detect benign breast

  12. Petrous apex lesions in the pediatric population

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Rupa [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Son, Hwa Jung [University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Cincinnati, OH (United States); Koch, Bernadette L. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

    2014-03-15

    A variety of abnormal imaging findings of the petrous apex are encountered in children. Many petrous apex lesions are identified incidentally while images of the brain or head and neck are being obtained for indications unrelated to the temporal bone. Differential considerations of petrous apex lesions in children include ''leave me alone'' lesions, infectious or inflammatory lesions, fibro-osseous lesions, neoplasms and neoplasm-like lesions, as well as a few rare miscellaneous conditions. Some lesions are similar to those encountered in adults, and some are unique to children. Langerhans cell histiocytosis (LCH) and primary and metastatic pediatric malignancies such as neuroblastoma, rhabomyosarcoma and Ewing sarcoma are more likely to be encountered in children. Lesions such as petrous apex cholesterol granuloma, cholesteatoma and chondrosarcoma are more common in adults and are rarely a diagnostic consideration in children. We present a comprehensive pictorial review of CT and MRI appearances of pediatric petrous apex lesions. (orig.)

  13. Imaging review of lipomatous musculoskeletal lesions

    Directory of Open Access Journals (Sweden)

    Burt Ashley M.

    2017-01-01

    Full Text Available Lipomatous lesions are common musculoskeletal lesions that can arise within the soft tissues, bone, neurovascular structures, and synovium. The majority of these lesions are benign, and many of the benign lesions can be diagnosed by radiologic evaluation. However, radiologic differences between benign and malignant lipomatous lesions may be subtle and pathologic correlation is often needed. The use of sonography, computed tomography (CT, and magnetic resonance imaging (MRI is useful not only in portraying fat within the lesion, but also for evaluating the presence and extent of soft tissue components. Lipomas make up most soft tissue lipomatous lesions, but careful evaluation must be performed to distinguish these lesions from a low-grade liposarcoma. In addition to the imaging appearance, the location of the lesion and the patient demographics can be utilized to help diagnose other soft tissue lipomatous lesions, such as elastofibroma dorsi, angiolipoma, lipoblastoma, and hibernoma. Osseous lipomatous lesions such as a parosteal lipoma and intraosseous lipoma occur less commonly as their soft tissue counterpart, but are also benign. Neurovascular and synovial lipomatous lesions are much rarer lesions but demonstrate more classic radiologic findings, particularly on MRI. A review of the clinical, radiologic, and pathologic characteristics of these lesions is presented.

  14. Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet.

    Science.gov (United States)

    Wan, Wenting; Li, Hongxiang; Xiang, Jiamei; Yi, Fan; Xu, Lijia; Jiang, Baoping; Xiao, Peigen

    2018-01-01

    Maca ( Lepidium meyenii Walpers) has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM) on high-fat, high-fructose diet (HFD)-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects. For 20 weeks, 6-week-old male golden hamsters were fed the following respective diets: (1) a standard diet, (2) HFD, (3) HFD supplemented with metformin, or (4) HFD supplemented with three doses of AEM (300, 600, or 1,200 mg/kg). After 20 weeks, the golden hamsters that received daily AEM supplementation presented with the beneficial effects of improved hyperlipidemia, hyperinsulinemia, insulin resistance, and hepatic steatosis in vivo . Based on the hepatic metabolomic analysis results, alterations in metabolites associated with pathological changes were examined. A total of 194 identified metabolites were mapped to 46 relative metabolic pathways, including those of energy metabolism. In addition, via in silico profiling for secondary maca metabolites by a joint pharmacophore- and structure-based approach, a compound-target-disease network was established. The results revealed that 32 bioactive compounds in maca targeted 16 proteins involved in metabolism disorder. Considering the combined metabolomics and virtual screening results, we employed quantitative real-time PCR assays to verify the gene expression of key enzymes in the relevant pathways. AEM promoted glycolysis and inhibited gluconeogenesis via regulating the expression of key genes such as Gck and Pfkm . Moreover, AEM upregulated tricarboxylic acid (TCA) cycle flux by changing the concentrations of intermediates and increasing the mRNA levels of Aco2 , Fh , and Mdh2 . In addition, the lipid

  15. Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet

    Directory of Open Access Journals (Sweden)

    Wenting Wan

    2018-04-01

    Full Text Available Maca (Lepidium meyenii Walpers has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM on high-fat, high-fructose diet (HFD-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects. For 20 weeks, 6-week-old male golden hamsters were fed the following respective diets: (1 a standard diet, (2 HFD, (3 HFD supplemented with metformin, or (4 HFD supplemented with three doses of AEM (300, 600, or 1,200 mg/kg. After 20 weeks, the golden hamsters that received daily AEM supplementation presented with the beneficial effects of improved hyperlipidemia, hyperinsulinemia, insulin resistance, and hepatic steatosis in vivo. Based on the hepatic metabolomic analysis results, alterations in metabolites associated with pathological changes were examined. A total of 194 identified metabolites were mapped to 46 relative metabolic pathways, including those of energy metabolism. In addition, via in silico profiling for secondary maca metabolites by a joint pharmacophore- and structure-based approach, a compound-target-disease network was established. The results revealed that 32 bioactive compounds in maca targeted 16 proteins involved in metabolism disorder. Considering the combined metabolomics and virtual screening results, we employed quantitative real-time PCR assays to verify the gene expression of key enzymes in the relevant pathways. AEM promoted glycolysis and inhibited gluconeogenesis via regulating the expression of key genes such as Gck and Pfkm. Moreover, AEM upregulated tricarboxylic acid (TCA cycle flux by changing the concentrations of intermediates and increasing the mRNA levels of Aco2, Fh, and Mdh2. In addition, the lipid

  16. Change in brain and lesion volumes after CEE therapies

    Science.gov (United States)

    Espeland, Mark A.; Hogan, Patricia E.; Resnick, Susan M.; Bryan, R. Nick; Robinson, Jennifer G.; Goveas, Joseph S.; Davatzikos, Christos; Kuller, Lewis H.; Williamson, Jeff D.; Bushnell, Cheryl D.; Shumaker, Sally A.

    2014-01-01

    Objectives: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen–based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. Methods: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Results: Total brain volume decreased an average of 3.22 cm3/y in the active arm and 3.07 cm3/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm3/y (p = 0.88). Conclusions: Conjugated equine estrogen–based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings. PMID:24384646

  17. Hock lesions and free-stall design.

    Science.gov (United States)

    Weary, D M; Taszkun, I

    2000-04-01

    We compared the prevalence and severity of skin lesions on the hocks of lactating dairy cows in southern British Columbia, comparing 20 farms using three common bedding surfaces: sawdust, sand, and geotextile mattresses. Skin lesions were scored at five positions on the hock. For each position we noted if the lesion showed inflammatory attributes, and then assigned a severity score. Of the 1752 lactating cows scored, 1267 cows (73%) had at least one hock lesion. Of those cows with lesions, 87% had lesions on both legs, 76% had lesions on more than one location on the hock, and 78% had a lesion of at least moderate severity (i.e., evidence of skin breakage or an area of hair loss >10 cm2). Lesions were most prevalent on farms that used geotextile mattresses (91% of cows) and least common on farms that used sand (24% of cows). Moreover, lesions on cows from farms using mattresses were more numerous and more severe than those on cows from sand-bedded farms. The prevalence and severity of lesions on farms using sawdust was intermediate. Lesions also varied in relation to location on the hock. For farms using geotextile mattresses, lesions were more common and more severe on the lateral surfaces of both the tuber calcis and the tarsal joint. On farms using sawdust, lesions were common on the dorsal surface of the tuber calcis and the lateral surfaces of both the tuber calcis and the tarsal joint. Lesions were rare on all five positions for cows from sand-bedded farms. Among the 10 farms sampled using sawdust, we found a significant negative relationship between the length of the stall and severity of lesions. For cows with lesions, the number and severity of lesions increased with age.

  18. Vital tooth with periapical lesion: spontaneous healing after conservative treatment

    Directory of Open Access Journals (Sweden)

    Hyun-Joo Kim

    2012-05-01

    Full Text Available It is often presumed that apical periodontitis follows total pulp necrosis, and consequently root canal treatment is commonly performed. Periapical lesion development is usually caused by bacteria and its byproduct which irritate pulp, develop pulpitis, and result in necrosis through an irreversible process. Afterwards, apical periodontitis occurs. This phenomenon is observed as an apical radiolucency in radiographic view. However, this unusual case presents a spontaneous healing of periapical lesion, which has developed without pulp necrosis in a vital tooth, through conservative treatment.

  19. Impact of radioguided occult lesion localization on the correct excision of malignant breast lesions. Effect of histology and tumor size

    International Nuclear Information System (INIS)

    Woll, J.P.P.; Garcia Vicente, A.M.; Gonzalez Garcia, B.; Delgado Portela, M.; Cordero Garcia, J.M.; Pardo Garcia, R.; Molino Trinidad, C.; Soriano Castrejon, A.M.; Cortes Romera, M.

    2011-01-01

    The aim of this study was to evaluate the impact of radioguided occult lesion localization (ROLL) in the correct location and excision of malignant breast lesions, and analyze if these results are affected by the histology and tumor size. A total of 105 patients with occult breast lesions were studied. The mean age was 55 years. An intralesional dose of 18.5 MBq of 99mTc-labeled macroaggregated human albumin (AMA) was administered using stereotaxic mammography or ultrasound. Surgical resection was carried out with the help of a gammadetector probe. In the histological study, disease-free margin was defined by a distance between the tumor lesion and the surgical margin of more than 1 mm. The possible influence of tumor histology and lesion diameter with respect to free/affected margins was analyzed. Correct radiotracer placement was achieved in 100/105 of the cases (95.2%). In the remaining 5 cases (4.8%), radiotracer placement was incorrect, with 2 of them being malignant lesions that were found by macroscopic inspection, and the other 3 having benign pathology. Among the malignant lesions (44 cases), correct placement of the radiotracer was achieved in 42 cases (95.5%). Of these 42 malignant lesions, in which the ROLL was correctly performed, free surgical margins were obtained in 24 cases (57.1%), while the other 18 (42.9%) had infiltrated surgical margins. The most common histological type among the malignant lesions was invasive ductal carcinoma (71.4%). The histological types with an increased frequency of infiltration of surgical margins were invasive and microinvasive cancer (94.4%). All the affected margins were in lesions greater than 10 mm, and the highest incidence was in those between 20 and 30 mm (55.5%). In our experience, the advantages of the ROLL technique are a precise localization of malignant breast lesions (95.5%) and an increased probability of a complete excision with free margins in more than one half of them. Nevertheless, special

  20. Eye lesions in pet birds.

    Science.gov (United States)

    Tsai, S S; Park, J H; Hirai, K; Itakura, C

    1993-03-01

    Amongst eye lesions in birds that died in quarantine, cataracts were the most common disorders (37/241, 15.4%), being prevalent in the annular pads of cockatiels (Nymphicus hollandicus), Amazon parrots (Amazona aestiva aestiva) and budgerigars (Melopsittacus undulatus). The incidence in male birds was more than twice that in females. Deposition of crystals, mostly in the cornea, was the second most frequent lesion (21/293, 8.7%), mainly found in cockatiels, parakeets (Psittacula krameri manillensis), Amazon parrots (Amazona aestiva aestiva), budgerigars and finches (Poephila gouldiae gouldiae). These corneal crystals were negative to PAS and Kossa's stains. Six parakeets (Psittacula krameri manillensis) had calcium salts deposited in the inner plexiform layer of the retina and occasionally in the iris and ciliary body. Neither inflammation nor neo-vascularization was observed when cataracts, corneal crystalline deposition, and retinal and ciliary calcification were present. Intranuclear inclusion bodies typical for papovavirus infection were found in the eyelids of six budgerigars (2.5%). Similar inclusions were simultaneously found in the pars ciliaris retinae (4, 1.7%), inner plexiform of retina (1, 0.4%) and anterior epithelium of the cornea (1, 0.4%). Other lesions such as candidial endophthalmitis, conjunctival cryptosporidiosis, corneal dystrophy, keratitis, corneal perforation and iridocyclitis, were occasional findings.

  1. Automatic segmentation of psoriasis lesions

    Science.gov (United States)

    Ning, Yang; Shi, Chenbo; Wang, Li; Shu, Chang

    2014-10-01

    The automatic segmentation of psoriatic lesions is widely researched these years. It is an important step in Computer-aid methods of calculating PASI for estimation of lesions. Currently those algorithms can only handle single erythema or only deal with scaling segmentation. In practice, scaling and erythema are often mixed together. In order to get the segmentation of lesions area - this paper proposes an algorithm based on Random forests with color and texture features. The algorithm has three steps. The first step, the polarized light is applied based on the skin's Tyndall-effect in the imaging to eliminate the reflection and Lab color space are used for fitting the human perception. The second step, sliding window and its sub windows are used to get textural feature and color feature. In this step, a feature of image roughness has been defined, so that scaling can be easily separated from normal skin. In the end, Random forests will be used to ensure the generalization ability of the algorithm. This algorithm can give reliable segmentation results even the image has different lighting conditions, skin types. In the data set offered by Union Hospital, more than 90% images can be segmented accurately.

  2. Evaluation of the Rib Lesions by Bone Scanning

    International Nuclear Information System (INIS)

    Park, Hyung Gun; Lee, Dong Soo; Lee, Myung Chul; Cho, Bo Youn; Koh, Chang Soon

    1983-01-01

    In order to establish criteria for distinguishing between occult fracture and metastases, we have reviewed 52 records of cancer patients and 24 of rib fracture patients referred for bone scanning. In 52 patients with biopsy-proven malignancy, multiple linear increased uptake of the ribs was found in 32 cases(61.5%), and was the most common finding. In 24 patients with rib fracture, all but 1 had fecal increased uptake of the ribs, and lesions almost always aligned in a row. By analyzing the appearance of rib lesions in total 76 patients, it was concluded that there is a high probability that rib lesions detected by bone scanning are bony metastases if 1) they are multiple linear as opposed to fecal, and 2) they are not aligned in the same location

  3. Inhibition of hexokinase-2 with targeted liposomal 3-bromopyruvate in an ovarian tumor spheroid model of aerobic glycolysis.

    Science.gov (United States)

    Gandham, Srujan Kumar; Talekar, Meghna; Singh, Amit; Amiji, Mansoor M

    2015-01-01

    The objective of this study was to evaluate the expression levels of glycolytic markers, especially hexokinase-2 (HK2), using a three-dimensional multicellular spheroid model of human ovarian adenocarcinoma (SKOV-3) cells and to develop an epidermal growth factor receptor-targeted liposomal formulation for improving inhibition of HK2 and the cytotoxicity of 3-bromopyruvate (3-BPA). Multicellular SKOV-3 tumor spheroids were developed using the hanging drop method and expression levels of glycolytic markers were examined. Non-targeted and epidermal growth factor receptor-targeted liposomal formulations of 3-BPA were formulated and characterized. Permeability and cellular uptake of the liposomal formulations in three-dimensional SKOV-3 spheroids was evaluated using confocal microscopy. The cytotoxicity and HK2 inhibition potential of solution form of 3-BPA was compared to the corresponding liposomal formulation by using cell proliferation and HK2 enzymatic assays. SKOV-3 spheroids were reproducibly developed using the 96-well hanging drop method, with an average size of 900 µm by day 5. HK2 enzyme activity levels under hypoxic conditions were found to be higher than under normoxic conditions (P<0.0001, Student's t-test, unpaired and two-tailed). Liposomal formulations (both non-targeted and targeted) of 3-BPA showed a more potent inhibitory effect (P<0.001, Student's t-test, unpaired and two-tailed) at a dose of 50 µM than the aqueous solution form at 3, 6, and 24 hours post administration. Similarly, the cytotoxic activity 3-BPA at various concentrations (10 µM-100 µM) showed that the liposomal formulations had an enhanced cytotoxic effect of 2-5-fold (P<0.0001, Student's t-test, unpaired and two-tailed) when compared to the aqueous solution form for both 10 µM and 25 µM concentrations. SKOV-3 spheroids developed by the hanging drop method can be used as a tumor aerobic glycolysis model for evaluation of therapies targeting the glycolytic pathway in cancer

  4. MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia

    Science.gov (United States)

    Guest, Paul C.; Iwata, Keiko; Kato, Takahiro A.; Steiner, Johann; Schmitt, Andrea; Turck, Christoph W.; Martins-de-Souza, Daniel

    2015-01-01

    Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from schizophrenia patients have demonstrated changes in activation of glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling schizophrenia. Treatment with MK-801 resulted in significant changes in the levels of glycolytic enzymes in all cell types. Most of the differences were found in oligodendrocytes, which had altered levels of hexokinase 1 (HK1), enolase 2 (ENO2), phosphoglycerate kinase (PGK), and phosphoglycerate mutase 1 after acute MK-801 treatment (8 h), and HK1, ENO2, PGK, and triosephosphate isomerase (TPI) following long term treatment (72 h). Addition of the antipsychotic clozapine to the cultures resulted in counter-regulatory effects to the MK-801 treatment by normalizing the levels of ENO2 and PGK in both the acute and long term cultures. In astrocytes, MK-801 affected only aldolase C (ALDOC) under both acute conditions and HK1 and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that

  5. The evaluation of the effect of attenuation correction on lesion detectability in whole-body FDG-PET

    International Nuclear Information System (INIS)

    Tomemori, Takashi; Uno, Kimiichi; Oka, Takashi; Suzuki, Takayuki; Tomiyoshi, Katsumi; Jin Wu

    2004-01-01

    The aim of this study was to compare the attenuation corrected and non-corrected FDG-PET images in patients with malignant lesions and to evaluate the effect of attenuation correction on lesion detectability. A total of 71 persons with 112 malignant lesions was examined. All subjects fasted for at least 4 hours before PET study and whole-body PET imaging was performed 45 min after the intravenous administration of FDG (mean dose: 273.8 MBq). Emission scans of 6 min and post-injection transmission scans of 6 min per bed position were used. The intensity of lesion uptake in FDG-PET image was visually classified into 3 grades; grade 2=the lesion was clearly identified in the maximum intensity projection (MIP) image of FDG-PET, grade 1=the lesion was not identified in MIP image but it can be identified in coronal image, grade 0=there was no contrast between lesion and background in both MIP and coronal image. Ninety-eight lesions (87.5%) were classified into same grade in both attenuation corrected and non-corrected image, but in 11 lesions (9.8%) attenuation corrected image was better lesion visualization than non-corrected image. All lesions divided between the primary lesions and the metastatic lesions. In 50 primary lesions, 43 lesions were depicted in both attenuation corrected and non-corrected image and other 7 lesions were not in both image. In 62 metastatic lesions, 50 lesions (80.7%) were classified into same grade in both attenuation corrected and non-corrected image, but in 10 lesions (16.1%) attenuation corrected image were better lesion visualization than non-corrected image. In the most cases, the lesions were depicted in both attenuation corrected and non-corrected image. In the primary lesions, the lesion detectability between attenuation corrected and non-corrected image was similar. But in some cases with the metastatic lesions, attenuation corrected image were better lesion visualization than non-corrected image. For asymptomatic patients, non

  6. The metabolic impact of β-hydroxybutyrate on neurotransmission: Reduced glycolysis mediates changes in calcium responses and KATP channel receptor sensitivity.

    Science.gov (United States)

    Lund, Trine M; Ploug, Kenneth B; Iversen, Anne; Jensen, Anders A; Jansen-Olesen, Inger

    2015-03-01

    Glucose is the main energy substrate for neurons, and ketone bodies are known to be alternative substrates. However, the capacity of ketone bodies to support different neuronal functions is still unknown. Thus, a change in energy substrate from glucose alone to a combination of glucose and β-hydroxybutyrate might change neuronal function as there is a known coupling between metabolism and neurotransmission. The purpose of this study was to shed light on the effects of the ketone body β-hydroxybutyrate on glycolysis and neurotransmission in cultured murine glutamatergic neurons. Previous studies have shown an effect of β-hydroxybutyrate on glucose metabolism, and the present study further specified this by showing attenuation of glycolysis when β-hydroxybutyrate was present in these neurons. In addition, the NMDA receptor-induced calcium responses in the neurons were diminished in the presence of β-hydroxybutyrate, whereas a direct effect of the ketone body on transmitter release was absent. However, the presence of β-hydroxybutyrate augmented transmitter release induced by the KATP channel blocker glibenclamide, thus giving an indirect indication of the involvement of KATP channels in the effects of ketone bodies on transmitter release. Energy metabolism and neurotransmission are linked and involve ATP-sensitive potassium (KATP ) channels. However, it is still unclear how and to what degree available energy substrate affects this link. We investigated the effect of changing energy substrate from only glucose to a combination of glucose and R-β-hydroxybutyrate in cultured neurons. Using the latter combination, glycolysis was diminished, NMDA receptor-induced calcium responses were lower, and the KATP channel blocker glibenclamide caused a higher transmitter release. © 2014 International Society for Neurochemistry.

  7. Clinical Significance of Contralateral Reactive Lesion in Vocal Fold Polyp and Cyst.

    Science.gov (United States)

    Cho, Jung-Hae; Choi, Yong-Sug; Joo, Young-Hoon; Park, Young-Hak; Sun, Dong-Il

    2018-01-01

    We investigated the clinical significance of contralateral reactive lesions in patients undergoing laryngeal microsurgery for benign vocal fold lesions such as vocal polyps and cysts. This was a retrospective, single institution cohort study. Patient medical records were reviewed for demographic characteristics; acoustic, aerodynamic, and perceptual analyses; and Voice Handicap Index score before and after laryngeal microsurgery. Definitive diagnoses were made via intraoperative microlaryngoscopic evaluations. Clinical parameters were assessed to identify risk factors for contralateral reactive lesions. We evaluated surgical outcome using voice analysis. We enrolled 268 patients (109 men and 159 women) with benign vocal fold lesions. A total of 195 (72.8%) had a contralateral reactive vocal fold lesion. A multivariable analysis revealed that being a never smoker and having a hoarseness duration ≥6 months, vocal polyps, and small primary lesions were independent risk factors for contralateral reactive lesions (P vocal fold lesions are frequently detected in patients with vocal polyp and cyst. The reactive lesions had an adverse effect on voice quality. Simultaneous excision of primary and contralateral reactive lesions may be an alternative treatment for better voice outcome. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  8. Gross and microscopic lesions in corals from Micronesia

    Science.gov (United States)

    Work, Thierry M.; Aeby, Greta S.; Hughen, Konrad A.

    2015-01-01

    The authors documented gross and microscopic morphology of lesions in corals on 7 islands spanning western, southern, and eastern Micronesia, sampling 76 colonies comprising 30 species of corals among 18 genera, with Acropora, Porites, and Montipora dominating. Tissue loss comprised the majority of gross lesions sampled (41%), followed by discoloration (30%) and growth anomaly (29%). Of 31 cases of tissue loss, most lesions were subacute (48%), followed by acute and chronic (26% each). Of 23 samples with discoloration, most were dark discoloration (40%), with bleaching and other discoloration each constituting 30%. Of 22 growth anomalies, umbonate growth anomalies composed half, with exophytic, nodular, and rugose growth anomalies composing the remainder. On histopathology, for 9 cases of dark discoloration, fungal infections predominated (77%); for 7 bleached corals, depletion of zooxanthellae from the gastrodermis made up a majority of microscopic diagnoses (57%); and for growth anomalies other than umbonate, hyperplasia of the basal body wall was the most common microscopic finding (63%). For the remainder of the gross lesions, no single microscopic finding constituted >50% of the total. Host response varied with the agent present on histology. Fragmentation of tissues was most often associated with algae (60%), whereas necrosis dominated (53%) for fungi. Two newly documented potentially symbiotic tissue-associated metazoans were seen in Porites and Montipora. Findings of multiple potential etiologies for a given gross lesion highlight the importance of incorporating histopathology in coral disease surveys. This study also expands the range of corals infected with cell-associated microbial aggregates.

  9. Non-invasive endodontic treatment of large periapical lesions

    Directory of Open Access Journals (Sweden)

    Harry Huiz Peeters

    2008-09-01

    Full Text Available Background: In most cases of large periapical radiolucent lesions of pulpal origin, we often encounter a dilemmatic situation, such as whether to either treat these cases endodontically or surgically. Development of techniques, instruments and root medicaments as well as the tendency toward minimally invasive treatment, all support dentists to treat those cases using the minimal invasive principle (i.e. endodontically instead of surgically. Purpose: The purpose of this paper is to report and discuss the managing of periapical lesions by endodontic no invasive treatment. Case management: The patient with large periapical lesions were treated with noninvasive endodontic treatment. After 6 months, patients in this report were asymptomatic and radiolucencies had disappeared. When the root canal treatment is done according to accepted clinical principles and under aseptic condition, including cleaning, shaping, abturating as well as proper diagnosis, the healing process of the infected area will occur. Conclusion: Some lesions, however, may not be treated conservatively and may require surgical treatment for total elimination of the lesions.

  10. Immunohistochemical Analysis of P63 Expression in Odontogenic Lesions

    Science.gov (United States)

    Atarbashi Moghadam, Saede; Atarbashi Moghadam, Fazele; Eini, Ebrahim

    2013-01-01

    P63 may have a role in tumorigenesis and cytodifferentiation of odontogenic lesions. We investigated the immunohistochemical expression of P63 in a total of 30 cases of odontogenic cysts and tumors. The percentage of positive cells was calculated in the lining of odontogenic cysts and islands of ameloblastoma. P63 expression was evident in all types of odontogenic lesions. P63 was expressed throughout the lining epithelium of odontogenic keratocyst except surface parakeratinized layer. In addition, calcifying odontogenic cyst showed P63 expression in all layers. In almost all radicular and dentigerous cysts, the basal and parabasal layers were immunoreactive. Peripheral cells of ameloblastoma expressed P63; however, stellate reticulum had weaker immunostaining. No significant difference in P63 expression was observed between studied lesions (P = 0.86). Expression of P63 in odontogenic lesions suggests that this protein is important in differentiation and proliferation of odontogenic epithelial cells. However, it seems that it could not be a useful marker to differentiate between aggressive and nonaggressive lesions. P63 also represents a progenitor or basal cell marker, and it is not expressed in mature differentiated cells. PMID:24350278

  11. Immunohistochemical Analysis of P63 Expression in Odontogenic Lesions

    Directory of Open Access Journals (Sweden)

    Saede Atarbashi Moghadam

    2013-01-01

    Full Text Available P63 may have a role in tumorigenesis and cytodifferentiation of odontogenic lesions. We investigated the immunohistochemical expression of P63 in a total of 30 cases of odontogenic cysts and tumors. The percentage of positive cells was calculated in the lining of odontogenic cysts and islands of ameloblastoma. P63 expression was evident in all types of odontogenic lesions. P63 was expressed throughout the lining epithelium of odontogenic keratocyst except surface parakeratinized layer. In addition, calcifying odontogenic cyst showed P63 expression in all layers. In almost all radicular and dentigerous cysts, the basal and parabasal layers were immunoreactive. Peripheral cells of ameloblastoma expressed P63; however, stellate reticulum had weaker immunostaining. No significant difference in P63 expression was observed between studied lesions (. Expression of P63 in odontogenic lesions suggests that this protein is important in differentiation and proliferation of odontogenic epithelial cells. However, it seems that it could not be a useful marker to differentiate between aggressive and nonaggressive lesions. P63 also represents a progenitor or basal cell marker, and it is not expressed in mature differentiated cells.

  12. Enamel lesions in development, classification in Costa Rican families

    International Nuclear Information System (INIS)

    Murillo Knudsen, Gina; Berrocal Salazar, Cristina

    2013-01-01

    Enamel lesions in development were identified and classified in patients of Llano Grande de Cartago, examined at the Facultad de Odontologia of the Universidad de Costa Rica. A guide is provided over the topic. 15 children and 2 Costa Rican adults were selected. Clinical examinations, radiographs and clinical photographs were used as data collection method. Dental defects of the enamel were classified according to the possible genetic causes and without genetic causes. Imperfect Amelogenesis (IA) was diagnosed in 10 of patients. Hypoplastic IA was determined in 3 siblings with autosomal recessive inheritance, for 16% of the total sample. Hypomineralized IA was identified in an adult and two of his sons, with autosomal dominant inheritance. The remaining 4 cases of IA have been sporadic. Lesions of dental fluorosis were determined in the Horowitz index in 4 individuals, from 2 unrelated families. Other defects unspecified of the enamel or hypoplasias were found in 3 individuals. Enamel lesions in development should be classified with precision, for the purpose to inform to patients affected about their condition, origin, prognosis and appropriate treatment. The basis are established to implement reliability in the construction of family genealogy, identification and classification of enamel lesions, as well as the probabilities of future generations to express the lesions in the enamel of temporary or permanent dentition [es

  13. Surgical management of metastatic lesions at the cervicothoracic junction

    Directory of Open Access Journals (Sweden)

    Joseph F Baker

    2015-01-01

    Full Text Available Purpose: The cervicothoracic junction (CTJ represents a transition from the semirigid thoracic spine to the mobile subaxial cervical spine. Pathologic lesions are prone to kyphotic deformity. The aim of this study was to review our experience with surgical stabilization of metastatic lesions affecting the CTJ (C7-T2. Materials and Methods: We reviewed all surgical stabilizations of metastatic spine lesions over the preceding 4 years in our institution. A total of 14 patients with CTJ lesions were identified. Case notes and radiology were reviewed to determine the presentation, outcomes, and specific complications. Results: The mean survival was 405 days (standard deviation [s.d.] 352. 8/14 died at a mean time from surgery of 193 days (s.d. 306. Most cases were a result of either lung or breast primary tumors. Half were stabilized with an anterior only approach and two had staged anterior-posterior. There were no cases of neurologic deterioration in this cohort as a result of surgery. There were two cases of deep surgical site infection and two documented cases of pulmonary embolus. There were no reported construct failures over the follow-up period. Conclusion: Patients with cervicothoracic metastatic lesions can be treated with either anterior or posterior approaches or a combination after considering each individual′s potential instability and disease burden.

  14. Role of Akt/PKB and PFKFB isoenzymes in the control of glycolysis, cell proliferation and protein synthesis in mitogen-stimulated thymocytes.

    Science.gov (United States)

    Houddane, Amina; Bultot, Laurent; Novellasdemunt, Laura; Johanns, Manuel; Gueuning, Marie-Agnès; Vertommen, Didier; Coulie, Pierre G; Bartrons, Ramon; Hue, Louis; Rider, Mark H

    2017-06-01

    Proliferating cells depend on glycolysis mainly to supply precursors for macromolecular synthesis. Fructose 2,6-bisphosphate (Fru-2,6-P 2 ) is the most potent positive allosteric effector of 6-phosphofructo-1-kinase (PFK-1), and hence of glycolysis. Mitogen stimulation of rat thymocytes with concanavalin A (ConA) led to time-dependent increases in lactate accumulation (6-fold), Fru-2,6-P 2 content (4-fold), 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase isoenzyme 3 and 4 (PFKFB3 and PFKFB4) protein levels (~2-fold and ~15-fold, respectively) and rates of cell proliferation (~40-fold) and protein synthesis (10-fold) after 68h of incubation compared with resting cells. After 54h of ConA stimulation, PFKFB3 mRNA levels were 45-fold higher than those of PFKFB4 mRNA. Although PFKFB3 could be phosphorylated at Ser461 by protein kinase B (PKB) in vitro leading to PFK-2 activation, PFKFB3 Ser461 phosphorylation was barely detectable in resting cells and only increased slightly in ConA-stimulated cells. On the other hand, PFKFB3 and PFKFB4 mRNA levels were decreased (90% and 70%, respectively) by exposure of ConA-stimulated cells to low doses of PKB inhibitor (MK-2206), suggesting control of expression of the two PFKFB isoenzymes by PKB. Incubation of thymocytes with ConA resulted in increased expression and phosphorylation of the translation factors eukaryotic initiation factor-4E-binding protein-1 (4E-BP1) and ribosomal protein S6 (rpS6). Treatment of ConA-stimulated thymocytes with PFK-2 inhibitor (3PO) or MK-2206 led to significant decreases in Fru-2,6-P 2 content, medium lactate accumulation and rates of cell proliferation and protein synthesis. These data were confirmed by using siRNA knockdown of PFKFB3, PFKFB4 and PKB α/β in the more easily transfectable Jurkat E6-1 cell line. The findings suggest that increased PFKFB3 and PFKFB4 expression, but not increased PFKFB3 Ser461 phosphorylation, plays a role in increasing glycolysis in mitogen

  15. Lesion Contrast Enhancement in Medical Ultrasound Imaging

    DEFF Research Database (Denmark)

    Stetson, Paul F.; Sommer, F.G.; Macovski, A.

    1997-01-01

    Methods for improving the contrast-to-noise ratio (CNR) of low-contrast lesions in medical ultrasound imaging are described. Differences in the frequency spectra and amplitude distributions of the lesion and its surroundings can be used to increase the CNR of the lesion relative to the background...

  16. The involvement of cation leaks in the storage lesion of red blood cells.

    Directory of Open Access Journals (Sweden)

    Joanna F Flatt

    2014-06-01

    Full Text Available Stored blood components are a critical life-saving tool provided to patients by health services worldwide. Red cells may be stored for up to 42 days, allowing for efficient blood bank inventory management, but with prolonged storage comes an unwanted side-effect known as the ‘storage lesion’, which has been implicated in poorer patient outcomes. This lesion is comprised of a number of processes that are inter-dependent. Metabolic changes include a reduction in glycolysis and ATP production after the first week of storage. This leads to an accumulation of lactate and drop in pH. Longer term damage may be done by the consequent reduction in anti-oxidant enzymes, which contributes to protein and lipid oxidation via reactive oxygen species. The oxidative damage to the cytoskeleton and membrane is involved in increased vesiculation and loss of cation gradients across the membrane. The irreversible damage caused by extensive membrane loss via vesiculation alongside dehydration is likely to result in immediate splenic sequestration of these dense, spherocytic cells. Although often overlooked in the literature, the loss of the cation gradient in stored cells will be considered in more depth in this review as well as the possible effects it may have on other elements of the storage lesion. It has now become clear that blood donors can exhibit quite large variations in the properties of their red cells, including microvesicle production and the rate of cation leak. Further study of stored red blood cells from donors known to have a high or low-rate of cation leak will shed more light on the relationship between cation gradients and the manifestation of the various elements of the storage lesion.

  17. Theory of pairwise lesion interaction

    International Nuclear Information System (INIS)

    Harder, Dietrich; Virsik-Peuckert, Patricia; Bartels, Ernst

    1992-01-01

    A comparison between repair time constants measured both at the molecular and cellular levels has shown that the DNA double strand break is the molecular change of key importance in the causation of cellular effects such as chromosome aberrations and cell inactivation. Cell fusion experiments provided the evidence that it needs the pairwise interaction between two double strand breaks - or more exactly between the two ''repair sites'' arising from them in the course of enzymatic repair - to provide the faulty chromatin crosslink which leads to cytogenetic and cytolethal effects. These modern experiments have confirmed the classical assumption of pairwise lesion interaction (PLI) on which the models of Lea and Neary were based. It seems worthwhile to continue and complete the mathematical treatment of their proposed mechanism in order to show in quantitative terms that the well-known fractionation, protraction and linear energy transfer (LET) irradiation effects are consequences of or can at least be partly attributed to PLI. Arithmetic treatment of PLI - a second order reaction - has also the advantage of providing a prerequisite for further investigations into the stages of development of misrepair products such as chromatin crosslinks. It has been possible to formulate a completely arithmetic theory of PLI by consequently applying three biophysically permitted approximations - pure first order lesion repair kinetics, dose-independent repair time constants and low yield of the ionization/lesion conversion. The mathematical approach will be summarized here, including several formulae not elaborated at the time of previous publications. We will also study an application which sheds light on the chain of events involved in PLI. (author)

  18. Improved differentiation between MS and vascular brain lesions using FLAIR* at 7 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Kilsdonk, Iris D.; Wattjes, Mike P.; Lopez-Soriano, Alexandra; Jong, Marcus C. de; Graaf, Wolter L. de; Conijn, Mandy M.A.; Barkhof, Frederik [VU University Medical Center, Department of Radiology, De Boelelaan 1118, HZ, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Center, Department of Physics and Medical Technology, Amsterdam (Netherlands); Polman, Chris H. [VU University Medical Center, Department of Neurology, Amsterdam (Netherlands); Luijten, Peter R. [University Medical Center, Department of Radiology, Utrecht (Netherlands); Geurts, Jeroen J.G. [VU University, Department of Anatomy and Neurosciences, Amsterdam (Netherlands); Geerlings, Mirjam I. [University Medical Center, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands)

    2014-04-15

    To investigate whether a new magnetic resonance image (MRI) technique called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7 Tesla (T). We examined 16 MS patients and 16 age-matched patients with (risk factors for) vascular disease. 3D-FLAIR and T2*-weighted images were combined into FLAIR* images. Lesion type and intensity, perivascular orientation and presence of a hypointense rim were analysed. In total, 433 cerebral lesions were detected in MS patients versus 86 lesions in vascular patients. Lesions in MS patients were significantly more often orientated in a perivascular manner: 74 % vs. 47 % (P < 0.001). Ten MS lesions (2.3 %) were surrounded by a hypointense rim on FLAIR*, and 24 MS lesions (5.5 %) were hypointense on T2*. No lesions in vascular patients showed any rim or hypointensity. Specificity of differentiating MS from vascular lesions on 7-T FLAIR* increased when the presence of a central vessel was taken into account (from 63 % to 88 %), most obviously for deep white matter lesions (from 69 % to 94 %). High sensitivity remained (81 %). 7-T FLAIR* improves differentiation between MS and vascular lesions based on lesion location, perivascular orientation and presence of hypointense (rims around) lesions. circle A new MRI technique T2*-weighted fluid attenuation inversion recovery (FLAIR*) was investigated. circle FLAIR* at 7-T MRI combines FLAIR and T2* images into a single image. circle FLAIR* at 7 T does not require enhancement with contrast agents. (orig.)

  19. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    Directory of Open Access Journals (Sweden)

    Cassali Geovanni D

    2010-02-01

    Full Text Available Abstract Background It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. Methods A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER, progesterone receptor (PgR, high molecular weight cytokeratin (34βE-12, E-cadherin, Ki-67, HER-2 and P53 was perfomed. Results Columnar cell lesions were identified in 67 (53.1% of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2% were without and 26 (38.8% with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%. Sixty (89.5% of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors. The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Conclusions Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions.

  20. Automatic segmentation and volumetry of multiple sclerosis brain lesions from MR images

    Directory of Open Access Journals (Sweden)

    Saurabh Jain

    2015-01-01

    Full Text Available The location and extent of white matter lesions on magnetic resonance imaging (MRI are important criteria for diagnosis, follow-up and prognosis of multiple sclerosis (MS. Clinical trials have shown that quantitative values, such as lesion volumes, are meaningful in MS prognosis. Manual lesion delineation for the segmentation of lesions is, however, time-consuming and suffers from observer variability. In this paper, we propose MSmetrix, an accurate and reliable automatic method for lesion segmentation based on MRI, independent of scanner or acquisition protocol and without requiring any training data. In MSmetrix, 3D T1-weighted and FLAIR MR images are used in a probabilistic model to detect white matter (WM lesions as an outlier to normal brain while segmenting the brain tissue into grey matter, WM and cerebrospinal fluid. The actual lesion segmentation is performed based on prior knowledge about the location (within WM and the appearance (hyperintense on FLAIR of lesions. The accuracy of MSmetrix is evaluated by comparing its output with expert reference segmentations of 20 MRI datasets of MS patients. Spatial overlap (Dice between the MSmetrix and the expert lesion segmentation is 0.67 ± 0.11. The intraclass correlation coefficient (ICC equals 0.8 indicating a good volumetric agreement between the MSmetrix and expert labelling. The reproducibility of MSmetrix' lesion volumes is evaluated based on 10 MS patients, scanned twice with a short interval on three different scanners. The agreement between the first and the second scan on each scanner is evaluated through the spatial overlap and absolute lesion volume difference between them. The spatial overlap was 0.69 ± 0.14 and absolute total lesion volume difference between the two scans was 0.54 ± 0.58 ml. Finally, the accuracy and reproducibility of MSmetrix compare favourably with other publicly available MS lesion segmentation algorithms, applied on the same data using default

  1. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    International Nuclear Information System (INIS)

    Ferreira, Enio; Gobbi, Helenice; Saraiva, Bruna S; Cassali, Geovanni D

    2010-01-01

    It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34βE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed. Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions

  2. OK-432 sclerotherapy for benign cystic head and neck lesions

    International Nuclear Information System (INIS)

    Kim, Chang Hyun; Rho, Myung Ho; Lee, Sang Wook

    2003-01-01

    To evaluate the efficacy of OK-432 solution for slerotheraphy of cystic lesions of the head and neck. Nineteen cystic lesions comprising ten plunging ranulas, three simple ranulas, three cystic lymphangiomas, one first branchial cleft cyst and two unknown supraclavicular cysts considered to be lymphangiomas were treated by sucking out as much liquid content as possible and then injecting the same volume of OK-432 solution under ultrasound guidance. Patients were followed up clinically and radiologically. Follow-up sonography or CT- performed after a mean interval of nine months showed total or near-total shrinkage of four plunging ranulas. However, six such lesions recurred in spite of more than one (mean, two) sclerotherapy sessions. In cases involving two simple ranulas at the floor of the mouth, failure resulted from extracystic leakage of OK-432 solution via the puncture site. Two unilocular cystic lymphangiomas completely regressed during the follow-up period (mean, seven months), but the multiocular type showed a 65% volume reduction after 12 months. A first branchial cleft cyst was markedly reduced in size, with only a small cystic portion remaining after eight months, follow-up. Two supraclavicular cysts with straw-color fluid did not respond to sclerotherapy. OK-432 sclerotherapy of macrocystic lymphangiomas is an effective and promising alternative to surgery. For other cysts, however, including plunging ranula, efficacy, varied, and 64% of such lesions recurred

  3. OK-432 sclerotherapy for benign cystic head and neck lesions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Hyun; Rho, Myung Ho; Lee, Sang Wook [Masan Samsung Hospital, Masan (Korea, Republic of)

    2003-12-01

    To evaluate the efficacy of OK-432 solution for slerotheraphy of cystic lesions of the head and neck. Nineteen cystic lesions comprising ten plunging ranulas, three simple ranulas, three cystic lymphangiomas, one first branchial cleft cyst and two unknown supraclavicular cysts considered to be lymphangiomas were treated by sucking out as much liquid content as possible and then injecting the same volume of OK-432 solution under ultrasound guidance. Patients were followed up clinically and radiologically. Follow-up sonography or CT- performed after a mean interval of nine months showed total or near-total shrinkage of four plunging ranulas. However, six such lesions recurred in spite of more than one (mean, two) sclerotherapy sessions. In cases involving two simple ranulas at the floor of the mouth, failure resulted from extracystic leakage of OK-432 solution via the puncture site. Two unilocular cystic lymphangiomas completely regressed during the follow-up period (mean, seven months), but the multiocular type showed a 65% volume reduction after 12 months. A first branchial cleft cyst was markedly reduced in size, with only a small cystic portion remaining after eight months, follow-up. Two supraclavicular cysts with straw-color fluid did not respond to sclerotherapy. OK-432 sclerotherapy of macrocystic lymphangiomas is an effective and promising alternative to surgery. For other cysts, however, including plunging ranula, efficacy, varied, and 64% of such lesions recurred.

  4. Clinical experiences of NBI laryngoscope in diagnosis of laryngeal lesions

    Science.gov (United States)

    Qi, Xinmeng; Yu, Dan; Zhao, Xue; Jin, Chunshun; Sun, Changling; Liu, Xueshibojie; Cheng, Jinzhang; Zhang, Dejun

    2014-01-01

    Endoscopy is essential for the diagnosis and treatment of cancers derived from the larynx. However, a laryngoscope with conventional white light (CWL) has technical limitations in detecting small or superficial lesions on the mucosa. Narrow band imaging especially combined with magnifying endoscopy (ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. A total of 3675 patients who have come to the outpatient clinic and complained of inspiratory stridor, dyspnea, phonation problems or foreign body sensation, were enrolled in this study. We describe the glottic conditions of the patients. All 3675 patients underwent laryngoscopy equipped with conventional white light (CWL) and NBI system. 1149 patients received a biopsy process. And 1153 lesions were classified into different groups according to their histopathological results. Among all the 1149 patients, 346 patients (312 males, 34 females; mean age 62.2±10.5 years) were suspected of having a total of 347 precancerous or cancerous (T1 or T2 without lymphnode involvement) lesions of the larynx under the CWL. Thus, we expected to attain a complete vision of what laryngeal lesions look like under the NBI view of a laryngoscope. The aim was to develop a complete description list of each laryngeal conditions (e.g. polyps, papilloma, leukoplakia, etc.), which can serve as a criteria for further laryngoscopic examinations and diagnosis. PMID:25419362

  5. Benign clavicular lesions that may mimic malignancy

    International Nuclear Information System (INIS)

    Gerscovich, E.G.; Greenspan, A.; Szabo, R.M.

    1991-01-01

    Nontraumatic lesions of the clavicle are infrequent. Of these, malignant tumors are more common than benign lesions. From January 1988 to January 1990, we examined 17 patients with benign lesions of the clavicle; in 8, the morphologic appearance of the lesion raised the possibility of malignancy in the differential diagnosis. The radiologic findings in these patients are presented. We propose that the unique shape and embryologic development of the clavicle may contribute to the atypical, aggressive presentation of some benign lesions in that bone. (orig.)

  6. Quantitative angiography methods for bifurcation lesions

    DEFF Research Database (Denmark)

    Collet, Carlos; Onuma, Yoshinobu; Cavalcante, Rafael

    2017-01-01

    Bifurcation lesions represent one of the most challenging lesion subsets in interventional cardiology. The European Bifurcation Club (EBC) is an academic consortium whose goal has been to assess and recommend the appropriate strategies to manage bifurcation lesions. The quantitative coronary...... angiography (QCA) methods for the evaluation of bifurcation lesions have been subject to extensive research. Single-vessel QCA has been shown to be inaccurate for the assessment of bifurcation lesion dimensions. For this reason, dedicated bifurcation software has been developed and validated. These software...

  7. Solitary lucent epiphyseal lesions in children

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, D.J.; Azouz, E.M.

    1988-10-01

    We evaluated retrospectively the varying radiographic appearances of 15 solitary lucent epiphyseal lesions occurring in children. Imaging modalities used included plain films, conventional tomography, nuclear scintigraphy, and computed tomography. 40% of the lesions (6) were due to osteomyelitis. The remaining lesions included tuberculosis (1), foreign body granuloma (1), chondroblastoma (2), chondromyoxid fibroma (1), enchondroma (1), osteoid osteoma (2), and eosinophilic granuloma (1). Although the radiographic appearances of such lesions may be particularly characteristic, pathologic correlation is frequently necessary. The high incidence of osteomyelitis in our cases emphasizes its importance as a cause for a lucent epiphyseal lesion.

  8. Computerized tomography of orbital lesions

    International Nuclear Information System (INIS)

    Kuroiwa, Mayumi

    1981-01-01

    Two different types of computerized tomography scanners (CT scanner), i.e. a whole-body CT scanner (GE-CT/T8800) and a cerebral CT scanner (EMI-1010), were compared in the assessment and diagnosis of various orbital lesions. The whole-body CT scanner was found to be advantageous over the cerebral CT scanner for the following reasons: (1) CT images were more informative due to thinner slices associated with smaller-sized and larger-numbered matrices; (2) less artifacts derived from motion of the head or eyeball were produced because of the shorter scanning time; (3) with a devised gantry, coronal dissections were available whenever demanded. (author)

  9. Metatranscriptomics reveals overall active bacterial composition in caries lesions

    Directory of Open Access Journals (Sweden)

    Aurea Simón-Soro

    2014-10-01

    Full Text Available 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

  10. Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet

    Directory of Open Access Journals (Sweden)

    Da-Wei Huang

    2018-01-01

    Full Text Available This study investigated the ameliorative effect of gallic acid (GA on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study (p < 0.05. Western blot assay indicated that GA restored expression of insulin signaling-related proteins, such as insulin receptor (IR, protein kinase C-zeta (PKC-ζ, and glucose transporter-4 (GLUT4 in the perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK and pyruvate kinase (PK, and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL, which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM complications.

  11. Ultrasonographic findings of breast lesions

    International Nuclear Information System (INIS)

    Hwang, In Sung; Kim, Yang Soo; Suh, Hyoung Sim

    1990-01-01

    Authors retrospectively analyzed ultrasonographic findings of 61 cases of breast lesions which were proven pathologically at Daerim St. Mary's Hospital from May 1987 to February 1990. The results were as follows : 1. Of all 61 cases, there were 27 fibroadenomas, 13 fibrocystic diseases, 11 carcinomas, 8 abscesses, 1 sclerosing adenosis, and 1 intraductal papilloma. 2. Findings suggesting benignancy were smooth contour, round or oval shape, homogeneously echolucent internal echo, echogenic boundary echo, and posterior enhancement. In the cases of abscess, the findings were rather irregular contour, strong posterior enhancement, and dirty, inhomogeneous internal echo. While irregular and lobulated shape, inhomogeneous and mixed internal echo and pectoral muscle invasion were suggested for malignancy. 3. The sensitivity was 98% and the specificity 58% in benign mass excluding abscesses, 63% and 98% in abscesses, and 55% and 98% in carcinomas. In conclusion, ultrasonography is one of the excellent imaging modality for detecting breast lesions larger than 5 mm in size, but unfortunately some of the malignant tumors simulated benignancy, thus we considered fine needle aspiration biopsy and adjunctive imaging modalities such as film mammography must be followed for better detection of breast cancer

  12. Ultrasonographic findings of breast lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, In Sung; Kim, Yang Soo; Suh, Hyoung Sim [College of Medicine, Daerim St. Mary' s Hospital, Seoul (Korea, Republic of)

    1990-07-15

    Authors retrospectively analyzed ultrasonographic findings of 61 cases of breast lesions which were proven pathologically at Daerim St. Mary's Hospital from May 1987 to February 1990. The results were as follows : 1. Of all 61 cases, there were 27 fibroadenomas, 13 fibrocystic diseases, 11 carcinomas, 8 abscesses, 1 sclerosing adenosis, and 1 intraductal papilloma. 2. Findings suggesting benignancy were smooth contour, round or oval shape, homogeneously echolucent internal echo, echogenic boundary echo, and posterior enhancement. In the cases of abscess, the findings were rather irregular contour, strong posterior enhancement, and dirty, inhomogeneous internal echo. While irregular and lobulated shape, inhomogeneous and mixed internal echo and pectoral muscle invasion were suggested for malignancy. 3. The sensitivity was 98% and the specificity 58% in benign mass excluding abscesses, 63% and 98% in abscesses, and 55% and 98% in carcinomas. In conclusion, ultrasonography is one of the excellent imaging modality for detecting breast lesions larger than 5 mm in size, but unfortunately some of the malignant tumors simulated benignancy, thus we considered fine needle aspiration biopsy and adjunctive imaging modalities such as film mammography must be followed for better detection of breast cancer.

  13. Imaging in cardiac mass lesions

    International Nuclear Information System (INIS)

    Mundinger, A.; Gruber, H.P.; Dinkel, E.; Geibel, A.; Beck, A.; Wimmer, B.; Schlosser, V.

    1992-01-01

    In 26 patients with cardiac mass lesions confirmed by surgery, diagnostic imaging was performed preoperatively by means of two-dimensional echocardiography (26 patients), angiography (12 patients), correlative computed tomography (CT, 8 patients), and magnetic resonance imaging (MRI, 3 patients). Two-dimensional echocardiography correctly identified the cardiac masses in all patients. Angiography missed two of 12 cardiac masses; CT missed one of eight. MRI identified three of three cardiac masses. Although the sensitivity of two-dimensional echocardiography was high (100%), all methods lacked specificity. None of the methods allowed differentiation between myxoma (n=13) and thrombus (n=7). Malignancy of the lesions was successfully predicted by noninvasive imaging methods in all six patients. However, CT and MRI provided additional information concerning cardiac mural infiltration, pericardial involvement, and extracardiac tumor extension, and should be integrated within a preoperative imaging strategy. Thus two-dimensional echocardiography is the method of choice for primary assessment of patients with suspected cardiac masses. Further preoperative imaging by CT or MRI can be limited to patients with malignancies suspected on the grounds of pericardial effusion or other clinical results. (author)

  14. Small ubiquitin-like modifier 1 modification of pyruvate kinase M2 promotes aerobic glycolysis and cell proliferation in A549 human lung cancer cells

    Directory of Open Access Journals (Sweden)

    An S

    2018-04-01

    Full Text Available Shuxian An,1,* Liangqian Huang,2,3,* Ping Miao,1 Liang Shi,1 Mengqin Shen,1 Xiaoping Zhao,1 Jianjun Liu,1 Gang Huang1,3,4 1Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 2Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 3Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 4Shanghai University of Medicine and Health Sciences, Shanghai, China *These authors contributed equally to this work Objective: Lung cancer is the leading cause of cancer-related death worldwide. Aerobic glycolysis is considered the seventh hallmark of cancer. The M2 isoform of pyruvate kinase (PKM2 is an important rate-limiting enzyme in glycolytic pathway, and is strongly expressed in several types of cancer. Thus, understanding the underlying mechanisms of regulation of PKM2 is of great value for targeted therapy for lung cancer.Patients and methods: Seventy-three lung adenocarcinoma patients were analyzed in our study. The expression levels of PKM2 were analyzed by immunohistochemistry on tissues. The effect of small ubiquitin-like modifier 1 (SUMO1 on PKM2 expression was investigated using Western blot assay and quantitative polymerase chain reaction. PKM2 SUMO1 modification was determined by in vitro and in vivo SUMOylation assays. 18F-deoxyglucose uptake and lactate production measurements were conducted to research the levels of glycolysis. The level of oxidative phosphorylation in cells was determined by cellular oxygen consumption rate measurements. Cell proliferation assays were carried out to confirm the growth ability of tumor cells.Results: PKM2 was overexpressed in lung adenocarcinoma patients based on immunohistochemical staining. Patients with high PKM2 expression had reduced

  15. Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features

    Energy Technology Data Exchange (ETDEWEB)

    Kornaat, Peter R.; Sharma, Ruby; Bloem, Johan L.; Watt, Iain [Leiden University Medical Center, Department of Radiology, Leiden (Netherlands); Kloppenburg, Margreet; Botha-Scheepers, Stella A. [Leiden University Medical Center, Department of Rheumatology, Leiden (Netherlands); Hellio le Graverand, Marie-Pierre [Pfizer Groton, Groton, CT (United States); Coene, L.N.J.E.M. [Haga Hospital, Department of Orthopaedic Surgery, The Hague (Netherlands)

    2007-12-15

    It has been suggested that bone marrow edema-like (BME) lesions in the knee are associated with progression of osteoarthritis (OA). The purpose of our study in patients with OA was to evaluate prospectively changes of BME lesions over 2 years and their relationship with clinical features. Magnetic resonance (MR) images of the knee were obtained from 182 patients (20% male; aged 43-76 years; mean age 59 years) who had been diagnosed with familial symptomatic OA at multiple joint sites. MR images were made at baseline and at 2 years follow-up. BME lesions in 2 years were associated with clinical features assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. A total of 327 BME lesions were recorded. Total size of BME lesions changed in 90 patients (66%). Size of individual lesions changed in 147 foci (45%): new lesions appeared in 69 (21%), existing lesions disappeared in 32 (10%), increased in size in 26 (8%) and decreased in size in 20 (6%) lesions. Increase or decrease of BME lesions, over a 2-year time period, was not associated with severity of WOMAC scores. BME lesions fluctuated in the majority of patients with OA over a 2-year time period. These changes were not associated with severity of WOMAC scores at the study end point. (orig.)

  16. Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features

    International Nuclear Information System (INIS)

    Kornaat, Peter R.; Sharma, Ruby; Bloem, Johan L.; Watt, Iain; Kloppenburg, Margreet; Botha-Scheepers, Stella A.; Hellio le Graverand, Marie-Pierre; Coene, L.N.J.E.M.

    2007-01-01

    It has been suggested that bone marrow edema-like (BME) lesions in the knee are associated with progression of osteoarthritis (OA). The purpose of our study in patients with OA was to evaluate prospectively changes of BME lesions over 2 years and their relationship with clinical features. Magnetic resonance (MR) images of the knee were obtained from 182 patients (20% male; aged 43-76 years; mean age 59 years) who had been diagnosed with familial symptomatic OA at multiple joint sites. MR images were made at baseline and at 2 years follow-up. BME lesions in 2 years were associated with clinical features assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. A total of 327 BME lesions were recorded. Total size of BME lesions changed in 90 patients (66%). Size of individual lesions changed in 147 foci (45%): new lesions appeared in 69 (21%), existing lesions disappeared in 32 (10%), increased in size in 26 (8%) and decreased in size in 20 (6%) lesions. Increase or decrease of BME lesions, over a 2-year time period, was not associated with severity of WOMAC scores. BME lesions fluctuated in the majority of patients with OA over a 2-year time period. These changes were not associated with severity of WOMAC scores at the study end point. (orig.)

  17. Coexistence of pheochromocytoma with uncommon vascular lesions

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2012-01-01

    Full Text Available Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14% had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis.

  18. Computed tomography - guided cutting needle biopsy of pulmonary lesions

    International Nuclear Information System (INIS)

    Liao Shin Yu; Deheinzelin, Daniel; Younes, Riad N.; Chojniak, Rubens

    2002-01-01

    The purpose of this study was to report the experience of a radiology department in the use of computed tomography-guided cutting needle biopsy of pulmonary nodules, by evaluating diagnostic yield and incidence of complications. This is a retrospective analysis of 52 consecutive patients who underwent lung lesion biopsy guided by computed tomography, performed between May 1997 and May 2000. Thirty-five patients were male and 17 were female, with ages ranging from 5 to 85 years (median, 62 years). The size of the lesions ranged from 1.8 to 15 cm (median, 5.4 cm). In a total of 52 biopsies of lung lesions, 51 biopsies (98.1%) supplied appropriate material for histopathological diagnosis, with 9 diagnosed (17.3%) as benign and 42 (80.8%) as malignant lesions. Specific diagnosis was obtained in 44 (84.6%) biopsies: 4 benign (9.1%) and 40 (90.9%) malignant lesions. The sensitivity, specificity, and accuracy of the cutting needle biopsies for determining presence of malignancy were 96.8%, 100%, and 97.2%, respectively. Complications occurred in 9 cases (17.3%), including 6 cases (11.5%) of small pneumothorax, 1 (1.9%) of hemoptysis, 1 (1.9%) of pulmonary hematoma, and 1 (1.9%) of thoracic wall hematoma. All had spontaneous resolution. There were no complications requiring subsequent intervention. The high sensitivity and specificity of the method and the low rate of complications have established cutting needle biopsy as an efficient and safe tool for the diagnosis of lung lesions. In our hospital, cutting needle biopsy is considered a reliable procedure for the evaluation of indeterminate pulmonary nodules. (author)

  19. Computed tomographic evaluation of pulmonary mass lesion in chest radiography

    International Nuclear Information System (INIS)

    Choe, Kyu Ok

    1984-01-01

    Until recently, solitary coin lesion of pulmonary disease has been a conspicuous problem in radiologic diagnosis. It is now well informed that CT has offered high resolution with its objective CT numbers to provide additional information in terms of anatomic and pathologic changes. Here by the aid of CT, the authors has retrospectively patients with various shape of round masses thus illustrating the advantage of it over conventional X-ray in diagnosis. 1. Total 53 patients, including 34 males and 19 females, aging between 19 to 76 years old with nodule or mass of any size ranging 1 to 13 cm in diameter were observed. 2. On plain chest X-ray they were identified where 50 patients has single round nodular or mass, only one had two masses which were ecchinococcal cysts, and the rest two had invisible lesions, only detected by CT. 3. With philips tomoscan 310, CT scan was taken 12 mm thicken slice during quiet respiration. Using the ROI cursor the average CT number of the central area was calculated 1.0 cm in side the outer border of the mass. 4. As a consequence of their pathologic features, they were itemized to 4 group as 36 solid, 9 cystic, 4 consolidative and 4 cavitary lesions. 5. Correct diagnosis of 3 cystic lesions, 4 diffuse calcification, 1 A-V malformation were available by CT densitometry. 6. By the aid of better resolution and additional cross-sectional orientation of CT, 3 extrapulmonary lesions, 3 segmental consolidations, 2 bronchocele, and 2 solitary metastasis, were helpful in diagnosis. 7. Also helpful in determining the extent of intrathoracic extent of bronchogenic carcinoma for the same reason but given clues were not more than the ordinary. 8. However, the limitation of the CT densitometry led to miss diagnosis of 3 examples of cystic vs.solid lesions, and CT density of noncalcified granuloma together with bronchogenic carcinoma, did not have a clear cut separation in between.

  20. MRI and pathological findings of epileptogenic lesions removed surgically

    International Nuclear Information System (INIS)

    Moritake, Kouzo; Kikuchi, Haruhiko; Minamikawa, Jun

    1990-01-01

    MRI revealed focal cerebral lesions in 19 patients, 12 males and 7 females, who had suffered from disabling seizures refractory to medical therapy for over one year; the lengths of the periods of therapy ranged from one to 17 years; mean: 8.8 years. Their ages at surgery ranged from 3 to 46 years; mean: 15.2 years. The results of other preoperative and intraoperative examinations, including mobile long-term ambulatory EEG monitoring, local CBF two-dimensional imaging by SPECT, and intraoperative cortical EEG, justified the surgical resection of those lesions revealed by MRI. These lesions were removed totally or subtotally. The pathological findings of the excised lesions were neuronal loss and gliosis in 10 cases (porencephaly, 2; arachnoid cyst, 3; post-traumatic scar, 1; nonspecific infarct, 4), hamartomatous pathology in 5 (hemartoma, 1; tuberous sclerosis, 4), and neoplasm in 4 (low-grade astrocytoma, 2; oligodendroglioma, 1; epidermoid, 1). The common pathological feature of these lesions was the proliferation of abnormal glial cells, which are sensitive to MRI imaging, especially to T 2 -weighted images. The postoperative follow-up terms of these 19 patients ranged from 6 to 23 months; mean: 15 months. Epileptic attacks had ceased in 12 of the 19 patients (63%), and there had been a marked improvement in both the frequency and severity of attacks in another 4. No permanent surgical complications or worsening of the seizures were seen in any patient. In conclusion, MRI is sensitive to epileptogenic lesions in patients with medically intractable epilepsy and is helpful in defining their configurations and margins and in planning the surgical approach. (author)

  1. Association between selected oral pathogens and gastric precancerous lesions.

    Directory of Open Access Journals (Sweden)

    Christian R Salazar

    Full Text Available We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans and dental caries (Streptococcus mutans and S. sobrinus. There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87-2.12, P. gingivalis (OR = 1.12, 0.67-1.88 and T. denticola (OR = 1.34, 0.83-2.12 measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13-5.56 among those with ≥ median of percent tooth sites with PD ≥ 3 mm, compared with no association among those below the median (OR = 0.86, 0.43-1.72. A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03-0.06. Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.

  2. Skin lesions in hospitalized cases of dengue Fever.

    Science.gov (United States)

    Saleem, Khawer; Shaikh, Irfan

    2008-10-01

    To determine the frequency and types of skin lesions in cases of dengue fever in patients admitted in three hospitals of Karachi. Case series. Three tertiary care hospitals of Karachi, from November 2006 to February 2007. One hundred patients of dengue fever with positive anti-dengue Immunoglobulin M (IgM) serology were included in the study. The admitted patients in PNS Shifa Hospital, Jinnah Postgraduate Medical Centre (JPMC) and Civil Hospital, Karachi were selected for the study. Presenting features were noted. The patients were physically examined for the presence of skin and mucosal lesions and findings were recorded. Total and Differential Leukocyte Count (TLC and DLC), platelet count and Liver Function Tests (LFTs) were done in all the patients. All the patients had low leukocyte and low platelet counts. The common presenting symptoms were high-grade fever with or without rigors, headache, body aches, backache, vomiting, sore throat with cough and generalized weakness (seen in 86% patients). The uncommon presenting features were diarrhea, abdominal pain, bleeding from gums and nosebleeds (seen in 14% patients). Sixty-eight (68%) patients had skin lesions. The most common skin presentation was generalized macular blanchable erythema involving trunk and limbs, seen in 44 (65%) cases. Discrete petechial lesions were seen on various body areas in 24 (35%) cases. Palmer erythema was seen in 20 (30%) patients. Generalized itching was seen in 16 (23%) cases. Isolated itching of palms and soles was seen in 20 (30%) cases. Twenty-eight (28%) patients had deranged LFTs. Out of those, 4 patients had raised serum bilirubin level whereas rest of the 24 had raised ALT. Dengue fever commonly presents with specific skin lesions. The skin lesions can be a clue to the diagnosis in difficult cases.

  3. Skin lesions in hospitalized cases of dengue fever

    International Nuclear Information System (INIS)

    Saleem, K.; Shaikh, I.

    2008-01-01

    To determine the frequency and types of skin lesions in cases of dengue fever in patients admitted in three hospitals of Karachi. One hundred patients of dengue fever with positive anti-dengue Immunoglobulin M (IgM) serology were included in the study. The admitted patients in PNS Shifa Hospital, Jinnah Postgraduate Medical Centre (JPMC) and Civil Hospital, Karachi were selected for the study. Presenting features were noted. The patients were physically examined for the presence of skin and mucosal lesions and findings were recorded. Total and Differential Leukocyte Count (TLC and DLC), platelet count and Liver Function Tests (LFTs) were done in all the patients. All the patients had low leukocyte and low platelet counts. The common presenting symptoms were high-grade fever with or without rigors, headache, body aches, backache, vomiting, sore throat with cough and generalized weakness (seen in 86% patients). The uncommon presenting features were diarrhea, abdominal pain, bleeding from gums and nosebleeds (seen in 14% patients). Sixty-eight (68%) patients had skin lesions. The most common skin presentation was generalized macular blanchable erythema involving trunk and limbs, seen in 44 (65%) cases. Discrete petechial lesions were seen on various body areas in 24 (35%) cases. Palmer erythema was seen in 20 (30%) patients. Generalized itching was seen in 16 (23%) cases. Isolated itching of palms and soles was seen in 20 (30%) cases. Twenty-eight (28%) patients had deranged LFTs. Out of those, 4 patients had raised serum bilirubin level whereas rest of the 24 had raised ALT. Dengue fever commonly presents with specific skin lesions. The skin lesions can be a clue to the diagnosis in difficult cases. (author)

  4. Skin lesions in hospitalized cases of dengue fever

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, K; Shaikh, I [Jinnah Postgraduate Medical Hospital, Karachi (Pakistan)

    2008-10-15

    To determine the frequency and types of skin lesions in cases of dengue fever in patients admitted in three hospitals of Karachi. One hundred patients of dengue fever with positive anti-dengue Immunoglobulin M (IgM) serology were included in the study. The admitted patients in PNS Shifa Hospital, Jinnah Postgraduate Medical Centre (JPMC) and Civil Hospital, Karachi were selected for the study. Presenting features were noted. The patients were physically examined for the presence of skin and mucosal lesions and findings were recorded. Total and Differential Leukocyte Count (TLC and DLC), platelet count and Liver Function Tests (LFTs) were done in all the patients. All the patients had low leukocyte and low platelet counts. The common presenting symptoms were high-grade fever with or without rigors, headache, body aches, backache, vomiting, sore throat with cough and generalized weakness (seen in 86% patients). The uncommon presenting features were diarrhea, abdominal pain, bleeding from gums and nosebleeds (seen in 14% patients). Sixty-eight (68%) patients had skin lesions. The most common skin presentation was generalized macular blanchable erythema involving trunk and limbs, seen in 44 (65%) cases. Discrete petechial lesions were seen on various body areas in 24 (35%) cases. Palmer erythema was seen in 20 (30%) patients. Generalized itching was seen in 16 (23%) cases. Isolated itching of palms and soles was seen in 20 (30%) cases. Twenty-eight (28%) patients had deranged LFTs. Out of those, 4 patients had raised serum bilirubin level whereas rest of the 24 had raised ALT. Dengue fever commonly presents with specific skin lesions. The skin lesions can be a clue to the diagnosis in difficult cases. (author)

  5. Primary study on lesion mimic mutants of rice (oryza sativa L.)

    International Nuclear Information System (INIS)

    Hao Zhongna; Zhang Hongzhi; Tao Rongixang

    2007-01-01

    Nineteen lesion mimic mutants (xsl1-19) of japonica rice Xiushui11 were obtained by γ-rays irradiation treatment. All mutants belonged to whole life lesion mimic. Lesion mimic of mutants didn't largen after tillering stage, leaves didn't wither, and no effect on the plants exsert spikes and seed. When the highest temperature in day exceeded 32 degree C in seedling stage, lesion mimic of all mutant expect xsl19 disappeared. Under 32 degree C, lesion mimic would appear gradually, and symptoms weren't inhibited by high temperature after 5 leaf stage. The plant heights of all lesion mimic mutants were 47.56-63.54 cm in the tillering stage, and that of CK was 83.75 cm; but the dwarf phenomenon of mutants only appeared before tillering stage, and didn't affect plant heights finally; the heading dates of mutants were the same to the CK, the ear length of all mutants were 9.43-15.19 cm, and that of CK was 16.41 cm; the total grain quantity per spike of all mutants were 88.17-165.33, and those of xsl19 and CK were 49.50 and 76.17. The results showed all lesion mimic mutants except xsl19 had short spikes and total grain quantity per spike increasing. All lesion mimic mutants were susceptible to Magnaporthe grisea, and they had no relationship with resistance. (authors)

  6. Fate of hypointense lesions on Gd-EOB-DTPA-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Akai, Hiroyuki; Matsuda, Izuru; Kiryu, Shigeru; Tajima, Taku; Takao, Hidemasa; Watanabe, Yasushi; Imamura, Hiroshi; Kokudo, Norihiro

    2012-01-01

    Purpose: To investigate the natural outcome and clinical implication of hypointense lesions in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. Materials and methods: Forty patients underwent Gd-EOB-DTPA-enhanced MRI for preoperative evaluation of HCC. Hypointense lesions in the hepatobiliary phase that were hypovascular 5 mm of more were extracted for follow-up. We performed a longitudinal study retrospectively for these lesions regardless of whether classical HCC developed or emerged in a different area from that of the lesions being followed. Results: Thirty one patients displayed 130 hypointense lesions on MRI and only nine showed no hypointense lesions. In total, 17 (13.1%) of 130 hypointense lesions on MRI developed into classical HCC. The cumulative rates for these lesions to develop into classical HCC were 3.2% at 1 year, 11.1% at 2 years and 15.9% at 3 years. The total occurrence rates of classical HCC (25.8% at 1 year, 52.6% at 2 years and 76.4% at 3 years) were higher compared to those regarding only occurrence of classical HCC from hypointense lesions on MRI (10.0% at 1 year, 35.6% at 2 years and 44.6% at 3 years), although no significant difference was observed (p = 0.073). Conclusions: Hypointense lesions that are detected in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI have some malignant potential, although treating these lesions aggressively in patients who already have HCC may be too severe.

  7. The significance of crystalline/chrysalis structures in the diagnosis of melanocytic and nonmelanocytic lesions.

    Science.gov (United States)

    Balagula, Yevgeniy; Braun, Ralph P; Rabinovitz, Harold S; Dusza, Stephen W; Scope, Alon; Liebman, Tracey N; Mordente, Ines; Siamas, Katherine; Marghoob, Ashfaq A

    2012-08-01

    Crystalline/chrysalis structures (CS) are white shiny streaks that can only be seen with polarized dermatoscopy. We sought to estimate the prevalence and assess the clinical significance of CS in melanocytic and nonmelanocytic lesions. This was a prospective observational study in which dermatoscopic assessment of lesions was recorded in consecutive patients examined during a 6-month period. In addition, a data set of biopsy-proven melanomas was retrospectively analyzed. In all, 11,225 lesions in 881 patients were prospectively examined. Retrospectively, 229 melanomas imaged with polarized dermatoscopy were analyzed. In the prospective data set, a median of 12.7 lesions (range, 1-54) were evaluated per patient. None of clinically diagnosed Clark nevi (n = 9750, 86.8%) demonstrated CS. Overall, CS were observed in 206 (1.8%) lesions, most commonly dermatofibromas and scars among nonbiopsied lesions. A total of 265 (2.4%) lesions were biopsied, including 20 melanomas and 36 nevi. Among biopsied malignant lesions, CS were most commonly observed in basal cell carcinoma (47.6%) and invasive melanomas (84.6%). Melanomas were more likely to have CS than biopsied nevi (odds ratio = 9.7, 95% confidence interval 2.7-34.1). In the retrospective data set, CS were more commonly observed among invasive melanomas (41%) compared with in situ melanomas (17%) (odds ratio = 3.4, 95% confidence interval 1.9-6.3, P < .001). The prevalence of CS correlated with increased melanoma thickness (P = .001). Biopsied lesions represent a small percentage of the total number of lesions evaluated. Among biopsied malignant lesions, CS are most commonly observed in basal cell carcinoma and invasive melanomas and rarely seen in nevi. In melanoma, CS may reflect increased tumor thickness and progression. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  8. Comparative clinical characteristics of neuromyelitis optica spectrum disorders with and without medulla oblongata lesions.

    Science.gov (United States)

    Wang, Yanqiang; Zhang, Lei; Zhang, Bingjun; Dai, Yongqiang; Kang, Zhuang; Lu, Ciyong; Qiu, Wei; Hu, Xueqiang; Lu, Zhengqi

    2014-05-01

    Brainstem involvement, especially the medulla oblongata (MO), has been reported in neuromyelitis optica spectrum disorders (NMOSDs). The purpose of this study was to investigate retrospectively and compare clinical, laboratory, and imaging features of NMOSDs with and without MO lesions. A total of 170 patients with NMOSDs were enrolled, including 44 patients with MO lesions and 126 patients without MO lesions. Clinical features, laboratory tests, and magnetic resonance imaging findings among these patients were assessed. MO lesions were found in 25.9 % of the NMOSDs patients. The mean duration was 13 months. Patients with MO lesions had a higher Annualized relapse rate and Expanded Disability Status Score Scale. Headache, dizziness, nystagmus, dysarthria, intractable hiccup and nausea, choking cough or dysphagia, movement disorders, and neuropathic pain were more common in MO lesion patients. Patients with MO lesions were more frequently complicated with thyroid diseases. Multiple brain involvement, More importantly, Longitudinally extensive transverse myelitis were more frequently found in patients with MO lesions. MO lesions might be a symbol of more severe neurologic deficits and worse prognosis of NMOSDs.

  9. Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions

    Energy Technology Data Exchange (ETDEWEB)

    Zech, Wolf-Dieter; Schwendener, Nicole; Jackowski, Christian [University of Bern, Institute of Forensic Medicine, Bern (Switzerland); Persson, Anders; Warntjes, Marcel J. [University of Linkoeping, Center for Medical Image Science and Visualization (CMIV), Linkoeping (Sweden)

    2015-07-15

    Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. (orig.)

  10. Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions

    International Nuclear Information System (INIS)

    Zech, Wolf-Dieter; Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J.

    2015-01-01

    Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. (orig.)

  11. An Epidemiological Study of Oral Mucosal Lesions in Karnataka State, India

    Directory of Open Access Journals (Sweden)

    K. V. V Prasad

    2004-01-01

    Full Text Available This article presents oral mucosal lesions findings from a state oral health survey of Karnataka, India. A total of 46,579 subjects aged 1-4 to 65+ years were selected by using multistage-cluster-stratified random sampling method and subjects were examined by 32 dentists trained in standardized clinical diagnostic criteria for oral mucosal lesions. In the present study, 7.53% of subjects had one or more oral mucosal lesions, in which, male subjects (9.41 % had a significantly higher prevalence of lesions compared to female subjects (4.38%; urban subjects (11.61% had a significantly higher prevalence than rural subjects (5.01 % and the Christian subjects had a significantly higher prevalence of lesions than the Hindus, Muslims and others (F=211.594, <0.001, S. The observed prevalence of oral mucosal lesions increased with age (r=0.8174, P<0.05, S, which is statistically significant. The most prevalent lesions observed were Leukoplakia (1.73%, Lichen planus (2.02% Ulceration (0.73%, Candidiasis (0.94% and Abscess (1.05%. The maximum number of lesions was seen in sulci (7.33% and the minimum number of lesions was seen in lips (0.02%. Differences in prevalence were analyzed by sex, religion, location and geographical area.

  12. Use of shear wave elastography to differentiate benign and malignant breast lesions.

    Science.gov (United States)

    Çebi Olgun, Deniz; Korkmazer, Bora; Kılıç, Fahrettin; Dikici, Atilla Süleyman; Velidedeoğlu, Mehmet; Aydoğan, Fatih; Kantarcı, Fatih; Yılmaz, Mehmet Halit

    2014-01-01

    We aimed to determine the correlations between the elasticity values of solid breast masses and histopathological findings to define cutoff elasticity values differentiating malignant from benign lesions. A total of 115 solid breast lesions of 109 consecutive patients were evaluated prospectively using shear wave elastography (SWE). Two orthogonal elastographic images of each lesion were obtained. Minimum, mean, and maximum elasticity values were calculated in regions of interest placed over the stiffest areas on the two images; we also calculated mass/fat elasticity ratios. Correlation of elastographic measurements with histopathological results were studied. Eighty-three benign and thirty-two malignant lesions were histopathologically diagnosed. The minimum, mean, and maximum elasticity values, and the mass/fat elasticity ratios of malignant lesions, were significantly higher than those of benign lesions. The cutoff value was 45.7 kPa for mean elasticity (sensitivity, 96%; specificity, 95%), 54.3 kPa for maximum elasticity (sensitivity, 95%; specificity, 94%), 37.1 kPa for minimum elasticity (sensitivity, 96%; specificity, 95%), and 4.6 for the mass/fat elasticity ratio (sensitivity, 97%; specificity, 95%). SWE yields additional valuable quantitative data to ultrasonographic examination on solid breast lesions. SWE may serve as a complementary tool for diagnosis of breast lesions. Long-term clinical studies are required to accurately select lesions requiring biopsy.

  13. Evaluation of mast cell counts and microvessel density in reactive lesions of the oral cavity

    Directory of Open Access Journals (Sweden)

    Maryam Kouhsoltani

    2016-12-01

    Full Text Available Background. Reliable immunohistochemical assays to assess the definitive role of mast cells (MCs and angiogenesis in the pathogenesis of oral reactive lesions are generally not available. The aim of the present study was to evaluate mast cell counts (MCC and microvessel density (MVD in oral reactive lesions and determine the correlation between MCC and MVD. Methods. Seventy-five cases of reactive lesions of the oral cavity, including pyogenic granuloma, fibroma, peripheral giant cell granuloma, inflammatory fibrous hyperplasia, peripheral ossifying fibroma (15 for each category were immunohisto-chemically stained with MC tryptase and CD31. Fifteen cases of normal gingival tissue were considered as the control group. The mean MCC and MVD in superficial and deep connective tissues were assessed and total MCC and MVD was computed for each lesion. Results. Statistically significant differences were observed in MCC and MVD between the study groups (P < 0.001. MC tryptase and CD31 expression increased in the superficial connective tissue of each lesion in comparison to the deep con-nective tissue. A significant negative correlation was not found between MCC and MVD in oral reactive lesions (P < 0.001, r = -0.458. Conclusion. Although MCs were present in the reactive lesions of the oral cavity, a direct correlation between MCC and MVD was not found in these lesions. Therefore, a significant interaction between MCs and endothelial cells and an active role for MCs in the growth of oral reactive lesions was not found in this study.

  14. Total parenteral nutrition - infants

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007239.htm Total parenteral nutrition - infants To use the sharing features on this page, please enable JavaScript. Total parenteral nutrition (TPN) is a method of feeding that bypasses ...

  15. Total parenteral nutrition

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000177.htm Total parenteral nutrition To use the sharing features on this page, please enable JavaScript. Total parenteral nutrition (TPN) is a method of feeding that bypasses ...

  16. Technique of total thyroidectomy

    International Nuclear Information System (INIS)

    Rao, R.S.

    1999-01-01

    It is essential to define the various surgical procedures that are carried out for carcinoma of the thyroid gland. They are thyroid gland, subtotal lobectomy, total thyroidectomy and near total thyroidectomy

  17. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  18. Total well dominated trees

    DEFF Research Database (Denmark)

    Finbow, Arthur; Frendrup, Allan; Vestergaard, Preben D.

    cardinality then G is a total well dominated graph. In this paper we study composition and decomposition of total well dominated trees. By a reversible process we prove that any total well dominated tree can both be reduced to and constructed from a family of three small trees....

  19. 'Emotional Intelligence': Lessons from Lesions.

    Science.gov (United States)

    Hogeveen, J; Salvi, C; Grafman, J

    2016-10-01

    'Emotional intelligence' (EI) is one of the most highly used psychological terms in popular nomenclature, yet its construct, divergent, and predictive validities are contentiously debated. Despite this debate, the EI construct is composed of a set of emotional abilities - recognizing emotional states in the self and others, using emotions to guide thought and behavior, understanding how emotions shape behavior, and emotion regulation - that undoubtedly influence important social and personal outcomes. In this review, evidence from human lesion studies is reviewed in order to provide insight into the necessary brain regions for each of these core emotional abilities. Critically, we consider how this neuropsychological evidence might help to guide efforts to define and measure EI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Imaging of extradural spinal lesions

    International Nuclear Information System (INIS)

    Ahlhelm, F.; Schulte-Altedorneburg, G.; Naumann, N.; Reith, W.; Nabhan, A.

    2006-01-01

    There is a wide variety of spinal extradural tumors. In addition to real neoplasms, degenerative diseases, congenital abnormalities and inflammatory disorders can be causes of extradural masses. Due to the bony boundary of the spinal canal, both benign as well as malignant masses can cause progressive neurological deficits including paraplegia. Most of the spinal tumors are benign (hemangioma of the vertebral body, degenerative diseases). In younger patients congenital abnormalities and primary tumors of the spine have to be considered, whereas in adults the list of differential diagnoses should include secondary malignancies such as metastases and lymphomas as well as metabolic disorders such as osteoporotic vertebral compression fracture and Paget's disease. Cross-sectional imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) of the spine often help to make a specific diagnosis of extradural spinal lesions and represent important tools for tumor staging and preoperative evaluation. (orig.) [de

  1. Cutaneous lesions in new born

    Directory of Open Access Journals (Sweden)

    Sachdeva Meenakshi

    2002-11-01

    Full Text Available Five hundred unselected newborn babies delivered in the Department of Obstetrics and Gynaecology, Unit II of SGBT Hospital attached to Government Medical College, Amritsar during April 2000 to October 2000 were examined for cutaneous lesions daily for the first five days after birth. Different cutaneous lesions were seen in 474(94. 8% newborns. The physiological skin changes observed in order of frequency were Epstein pearls in 305(61%, Mongolian spot in 301(60. 2%, superficial cutaneous desquamation in 200(40%, icterus in 128(25. 6%, milia in 119(23. 8%, sebaceous gland hyperplasia in 107 (21. 4%, occipital alopecia in 94(18. 8%, lanugo in 72(14. 4%, peripheral cyanosis in 47(9. 4%, breast hypertrophy in 29(5. 8% and miniature puberty in 28(5. 6% newborns. Of the transient non-infective skin diseases, erythema toxicum neonatorum was observed most commonly in 105(21 %, followed by miliaria rubra in 103(20. 6% and acne neonatorum in 27(5. 4% newborns. The naevi and other developmental defects in the descending order were salmon patch in 69(13. 8%, congenital melanocytic noevi in 10(2%, accessory tragi in 3(0.6%, spina bifida in 2(0.4%, hydrocephalus in 1(0.2% and poliosis in 1(0.2% newborns. Cradle cap was the only dermatitis observed in 50(10% newborns. One (0.2% case each of Harlequin ichthyosis and labial cyst was seen.

  2. Imaging pattern of calvarial lesions in adults

    Energy Technology Data Exchange (ETDEWEB)

    Garfinkle, Jarred; Melancon, Denis; Cortes, Maria; Tampieri, Donatella [Montreal Neurological Institute and Hospital-McGill University Health Center, Department of Diagnostic and Interventional Neuroradiology, Montreal, Quebec (Canada)

    2011-10-15

    Calvarial lesions often present themselves as clinically silent findings on skull radiographs or as palpable masses that may cause localized pain or soreness. This review aims to explore the radiographic, computed tomography (CT), and magnetic resonance imaging (MRI) characteristics of calvarial neoplastic, inflammatory, and congenital lesions that are common in adults in order to facilitate a structured approach to their diagnosis and limit the differential diagnosis. In addition to reviewing the literature, we reviewed the records of 141 patients of the Montreal Neurological Institute and Hospital with radiologically documented calvarial lesions between 2001 and June 2009. CT is ideal for detecting bony lesions and is helpful in precisely localizing a lesion pre-surgically. MRI is best at identifying intradiploic lesions before they affect the cortical tables and is able to establish extraosseous involvement, especially when paramagnetic contrast is employed. (orig.)

  3. Detection of Fundus Lesions Using Classifier Selection

    Science.gov (United States)

    Nagayoshi, Hiroto; Hiramatsu, Yoshitaka; Sako, Hiroshi; Himaga, Mitsutoshi; Kato, Satoshi

    A system for detecting fundus lesions caused by diabetic retinopathy from fundus images is being developed. The system can screen the images in advance in order to reduce the inspection workload on doctors. One of the difficulties that must be addressed in completing this system is how to remove false positives (which tend to arise near blood vessels) without decreasing the detection rate of lesions in other areas. To overcome this difficulty, we developed classifier selection according to the position of a candidate lesion, and we introduced new features that can distinguish true lesions from false positives. A system incorporating classifier selection and these new features was tested in experiments using 55 fundus images with some lesions and 223 images without lesions. The results of the experiments confirm the effectiveness of the proposed system, namely, degrees of sensitivity and specificity of 98% and 81%, respectively.

  4. [Pediatric lung lesions: a clinicopathological study of 215 cases].

    Science.gov (United States)

    Niu, Huilin; Wang, Fenghua; Liu, Wei; Wang, Yong; Chen, Zhengrong; Gao, Qiu; Yi, Peng; Li, Liping; Zeng, Rongxin

    2015-09-01

    To investigate clinical and pathological features of lung lesions in children. Clinical manifestations, radiologic imaging, histopathological features and immunohistochemical results were analyzed in 215 cases of lung lesions in children. A total of 215 cases of lung lesions in children aged 0 day to 13 years (average age of 27.2 months and the median age of 18.0 months) were selected, including 137 male and 78 female patients with a male to female ratio of 1.76:1.00. The incidence of congenital lung disease was higher in patients of less than 1 year old than those of over 1 year old age, and the difference of the two groups was statistically significant (P = 0.004). 142 cases had acquired lung diseases, and 73 cases had congenital bronchopulmonary dysplasia. Lung abscess was the most common lesion seen in 86 cases (40.0%), including 1 case of fungal abscess. Congenital pulmonary airway malformation (CPAM) was the second most common, seen in 44 patients (20.5%), including 20 cases of type 1, 18 cases of type 2 and 6 cases of type 4 CPAM. Pulmonary sequestration was found in 25 cases (11.6%) including 14 cases of intralobar type and 11 cases of extralobar type. Two cases of extralobar pulmonary sequestration showed simultaneous CPAM2 type 2 lesion. Other lesions included tuberculosis (13 cases, 6.0%), emphysema (12 cases, 5.6%), interstitial pneumonia (7 cases, 3.2%), pulmonary hemorrhage (6 cases, 2.8%), bronchogenic cyst (4 cases, 1.9%), bronchiolitis obliterans (2 cases, 0.9%), idiopathic pulmonary hemosiderin deposition disease (2 cases, 0.9%) and 1 cases of lung non-specific changes. 13 cases of neoplastic lesions (6.0%) were found, of which 11 cases were primary tumors (5.1%), including inflammatory myofibroblastic tumor in 5 patients (2.3%), pleuropulmonary blastoma in 5 cases (1 case of type I, 2 type II and 2 type III) and 1 case of mucoepidermoid carcinoma (0.5%) and 2 cases of metastatic tumors (hepatoblastoma and Wilm's tumor, 0.9%). Infectious diseases

  5. Hybrid Odontogenic Lesion: A Rare Entity

    Directory of Open Access Journals (Sweden)

    Reza Imani

    2017-03-01

    Full Text Available Hybrid tumors are very rare tumors composed of two different tumor entities, each of which conforms to an exactly defined tumor category. A 14-year-old boy was referred for an intraosseous painless lesion with a histopathological feature of multiple odontogenic lesions including calcifying odontogenic cyst, complex odontoma and ameloblastic fibro-odontoma. The final diagnosis considered to be a hybrid odontogenic lesion.

  6. Space Occupying Lesions in the Liver

    OpenAIRE

    Nasser Ebrahimi Daryani

    2009-01-01

    "nRadiology (imaging) plays a pivotal role for the diagnosis, staging, treatment planning, and follow-up of focal liver lesions. The differential diagnosis in patients presenting with a focal liver lesion is broad. "nThe size of the liver mass is an important consideration in guiding the evaluation. Lesions smaller than approximately 1.0 cm are commonly benign incidental findings on imaging studies, and in most cases represent small cysts, hemangiomas, or biliary hamartomas. Further...

  7. Benign Lesions of The Vocal Fold

    Directory of Open Access Journals (Sweden)

    Ozgur Surmelioglu

    2013-02-01

    Full Text Available Benign lesions of vocal folds are common disorders. Fifty percent of patients who have sound complaints are found to have these lesions after endoscopic and stroboscopic examinations. Benign vocal fold diseases are primarily caused by vibratory trauma. However they may also occur as a result of viral infections and congenital causes. These lesions are often presented with the complaints of dysphonia. [Archives Medical Review Journal 2013; 22(1.000: 86-95

  8. Proliferative changes in nonpalpable breast lesions detected by mammography

    International Nuclear Information System (INIS)

    Vega, A.; Delgado, A.; Ortega, E.; Garijo, F.; Mosquera, J.; Sogo, C.; Alvarez, A.

    2000-01-01

    To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs

  9. Deficit-lesion correlations in syntactic comprehension in aphasia.

    Science.gov (United States)

    Caplan, David; Michaud, Jennifer; Hufford, Rebecca; Makris, Nikos

    2016-01-01

    The effects of lesions on syntactic comprehension were studied in thirty-one people with aphasia (PWA). Participants were tested for the ability to parse and interpret four types of syntactic structures and elements - passives, object extracted relative clauses, reflexives and pronouns - in three tasks - object manipulation, sentence picture matching with full sentence presentation and sentence picture matching with self-paced listening presentation. Accuracy, end-of-sentence RT and self-paced listening times for each word were measured. MR scans were obtained and analyzed for total lesion volume and for lesion size in 48 cortical areas. Lesion size in several areas of the left hemisphere was related to accuracy in particular sentence types in particular tasks and to self-paced listening times for critical words in particular sentence types. The results support a model of brain organization that includes areas that are specialized for the combination of particular syntactic and interpretive operations and the use of the meanings produced by those operations to accomplish task-related operations. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. MRI appearance of stereotactic thalamic lesions in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Terada, Kousaku; Asakura, Tetsuhiko; Kasamo, Shizuya; Kusumoto, Kazuhiro; Niiro, Masaki [Kagoshima Univ. (Japan). Faculty of Medicine; Uetsuhara, Kouichi

    1990-04-01

    Stereotactic thalamotomy is a useful method of treatment in selected cases of Parkinsonism. Previously, the consequences of these stereotactic lesions have been assessed by means of their postoperative clinical effects and CT appearances. Now, however, MR imaging allows a clearer, three-dimensional demonstration of the lesion than does CT scanning; its appearance can now be correlated with the results obtained by the use of the radiofrequency method and its clinical effects. The authors have performed postoperative MR imaging on 12 patients with a total of 13 thalamotomies. The early postoperative MR appearance of these lesions is composed of two relatively clear and distinct parts. In T{sub 1}-weighted imaging, there is a central hyper-intense core and a low-intensity area surrounding it. In T{sub 2}-weighted imaging, there is a central hypo-intense core and a high-intensity area surrounding it. The late postoperative MR appearance is a low-intensity spot in T{sub 1}-weighted imaging and a high-intensity spot in T{sub 2}-weighted imaging. MR imaging is very useful for the postoperative evaluation of stereotactic thalamotomy in helping to identify the location of and the chronological change in the radiofrequency lesions. (author).

  11. Deficit-Lesion Correlations in Syntactic Comprehension in Aphasia

    Science.gov (United States)

    Caplan, David; Michaud, Jennifer; Hufford, Rebecca; Makris, Nikos

    2015-01-01

    The effects of lesions on syntactic comprehension were studied in thirty one people with aphasia (PWA). Participants were tested for the ability to parse and interpret four types of syntactic structures and elements -- passives, object extracted relative clauses, reflexives and pronouns – in three tasks – object manipulation, sentence picture matching with full sentence presentation and sentence picture matching with self-paced listening presentation. Accuracy, end-of-sentence RT and self-paced listening times for each word were measured. MR scans were obtained and analyzed for total lesion volume and for lesion size in 48 cortical areas. Lesion size in several areas of the left hemisphere was related to accuracy in particular sentence types in particular tasks and to self-paced listening times for critical words in particular sentence types. The results support a model of brain organization that includes areas that are specialized for the combination of particular syntactic and interpretive operations and the use of the meanings produced by those operations to accomplish task-related operations. PMID:26688433

  12. Lesion localization in aphasia without hemiparesis

    International Nuclear Information System (INIS)

    Komatsu, Midori; Senoh, Yoko; Okamoto, Koichi; Morimatsu, Mitsunori; Hirai, Shunsaku

    1983-01-01

    The distribution of the lesions responsible for aphasia unassociated with right-sided hemiparesis was evaluated by cranial computed tomography (CT) among stroke patients. In the Broca aphasia group were observed atypical aphasic symptoms, and the lesions were far more localized than in ordinary Broca one. In the Wernicke aphasia group showed relatively large lesions in the left superior temporal gyrus, sometimes extending to supramarginal and angular gyri, which caused such additional symptoms as apraxia without motor paresis in some cases. In the Transcortical motor aphasia group showed the occlusion of the left internal carotid artery, though without obvious abnormality at CT. In another patient a circumscribed low density lesion was disclosed in the area anterior and superior to so-called Broca's area. In the Transcortical sensory aphasia group, the lesion involved the borderzone supplied by the left middle and posterior cerebral arteries. In the Amnestic aphasia group showed a lesion in the left parietal lobe, while in another no remarkable change was demonstrated. In the Global aphasia group, one had multiple isolated lesions in both anterior and posterior speech areas. Another showed a large lesion involving the whole territory of the left middle cerebral artery. In the remaining one a high density area was observed in the left superior temporal, supramarginal and angular gyri, not extending to the frontal lobe beyond with sylvian fissure. Therefore, in interpreting CTs of such aphasic patients we must take account of not only the extent of the lesion but also the severity of destruction. (J.P.N.)

  13. Lesion localization in aphasia without hemiparesis

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Midori; Senoh, Yoko; Okamoto, Koichi; Morimatsu, Mitsunori; Hirai, Shunsaku (Gunma Univ., Maebashi (Japan). School of Medicine)

    1983-06-01

    The distribution of the lesions responsible for aphasia unassociated with right-sided hemiparesis was evaluated by cranial computed tomography (CT) among stroke patients. In the Broca aphasia group were observed atypical aphasic symptoms, and the lesions were far more localized than in ordinary Broca one. In the Wernicke aphasia group showed relatively large lesions in the left superior temporal gyrus, sometimes extending to supramarginal and angular gyri, which caused such additional symptoms as apraxia without motor paresis in some cases. In the Transcortical motor aphasia group showed the occlusion of the left internal carotid artery, though without obvious abnormality at CT. In another patient a circumscribed low density lesion was disclosed in the area anterior and superior to so-called Broca's area. In the Transcortical sensory aphasia group, the lesion involved the borderzone supplied by the left middle and posterior cerebral arteries. In the Amnestic aphasia group showed a lesion in the left parietal lobe, while in another no remarkable change was demonstrated. In the Global aphasia group, one had multiple isolated lesions in both anterior and posterior speech areas. Another showed a large lesion involving the whole territory of the left middle cerebral artery. In the remaining one a high density area was observed in the left superior temporal, supramarginal and angular gyri, not extending to the frontal lobe beyond with sylvian fissure. Therefore, in interpreting CTs of such aphasic patients we must take account of not only the extent of the lesion but also the severity of destruction.

  14. Thermophysical lesions caused by HZE particles

    International Nuclear Information System (INIS)

    Tobias, C.A.; Malachowski, M.; Nelson, A.; Philpott, D.E.

    1980-01-01

    This paper deals with a type of damage caused by heavy particles that may occur in subcellular structures. These lesions are called thermophysical radiation injury and are similar to damage produced in solids by HZE particles. This chapter summarizes some of the experimental evidence for the presence of these lesions in certain mammalian tissues including the retina, brain, cornea, lens of mice and seeds of corn. Of all tissues examined, only the cornea exhibited a type of lesion which would fulfill the criteria of thermophysical lesions

  15. MR imaging of sacral and perisacral lesions

    International Nuclear Information System (INIS)

    Wetzel, L.H.; Levine, E.; Murphey, M.D.

    1987-01-01

    This exhibit demonstrates the utility of MR imaging in evaluating sacral and perisacral lesions. Thirty-two lesions were studied using a superconducting 1.0-T MR imager. Eleven primary and 13 metastatic tumors, four congenital lesions, and four arachnoid cysts were evaluated. MR did not usually enable a more specific histologic diagnosis than other imaging techniques. However, extraosseous and proximal spinal extent of tumors was well defined without use of oral or intravenous contrast material. MR imaging is an excellent noninvasive technique for evaluating most sacral and perisacral lesions and is particularly helpful when precise tumor extent must be determined for treatment planning

  16. Visible and occult microscopic lesions of endometriosis

    Directory of Open Access Journals (Sweden)

    Khaleque Newaz Khan

    2014-11-01

    Full Text Available Endometriosis is a multifactorial disease mostly affecting women of reproductive age and is associated with chronic pelvic pain and infertility. Even after 300 years, most of the literature claims that pathogenesis and/or pathophysiology of endometriosis is still elusive. Recurrence of pain and lesion continues to occur after effective medical or surgical therapies. Once generated within the pelvis due to retrograde entry of menstrual debris, peritoneal endometriotic lesions time-dependently change their color appearance resulting from certain biochemical change within lesions. A variable pattern of endometriotic lesions within the pelvis can be detected by laparoscopy as visible peritoneal endometriosis. It is generally believed that besides ovarian steroid hormones, the growth of endometriosis can be regulated by the innate immune system in the pelvic microenvironment by their interaction with endometrial cells and immune cells. Even with the careful eyes of an expert surgeon, we may sometimes miss detecting peritoneal lesion within the peritoneal cavity or deep into the peritoneum. In such a case, random collection of normal peritoneum may carry the possibility to identify some hidden endometriotic lesions by microscopy and these lesions can be named as occult (invisible microscopic endometriosis (OME. Here, we discuss the color appearance of peritoneal lesions and activity of these lesions by analysis of a panel of activity markers. Finally we discuss our recent findings on OME, their biological and clinical significance, and try to make a possible link in the origin between visible endometriosis and OME.

  17. Measuring Cutaneous Lesions: Trends in Clinical Practice.

    Science.gov (United States)

    Zhang, Shali; Blalock, Travis W

    2018-03-01

    Knowing the size of a cutaneous lesion can be important for tracking its progression over time, selecting the proper treatment modality, surgical planning, determining prognosis, and accurate billing. However, providers vary in their consistency, accuracy, and methods of measuring cutaneous lesions. To investigate the clinical practices of US dermatologists and dermatologic surgeons regarding how they determine the size of cutaneous lesions. A survey was electronically distributed to members of the American Society for Dermatologic Surgery. Four hundred twenty-six dermatologists completed the online survey. When a lesion is suspected to be malignant, 85% of respondents obtained exact measurements most, if not all, of the time; however, only 8% did for benign lesions. Most providers determined lesion sizes themselves rather than delegating to staff. When performing visual estimation, approximately three-quarters believed that they were accurate to within 1 to 2 mm. The top reasons for obtaining exact measurements were for tracking atypical pigmented lesions, determining treatment pathways, and accurate billing. The majority of respondents believed that lesion size affected management decisions; however, the need for exact measurement remains controversial, particularly for benign lesions. Future studies may investigate whether taking exact versus estimated measurements has an effect on outcomes.

  18. Articular cartilage damage with intramedullary lesion (bone bruise) in anterior cruciate ligament rupture

    International Nuclear Information System (INIS)

    Ide, Shuya; Ohdera, Toshihiro; Tokunaga, Masami; Hiroshima, Shiro; Yoshimoto, Eiji

    2002-01-01

    We evaluated the relationship between the intramedullary lesion on MRI and cartilage damage in patients associated with acute anterior cruciate ligament (ACL) rupture. Thirty-two cases documented by MRI and arthroscopy within one month from injury underwent ACL reconstruction using ST-G, and arthroscopy was performed again after surgery. The mean term between reconstruction and postoperative arthroscopy was twelve months. The cartilage damage on arthroscopy was compared with the intramedullary lesion on MRI. Cartilage damage was observed in 9 cases (28.1%) during the initial arthroscopy and in 16 cases (50.0%) during the second arthroscopy. Intramedullary lesion was detected in all 32 cases (total: 73 lesions) on MRI. Intramedullary lesion leading to cartilage damage was common in the geographic-type lateral femoral condyle. There was significant difference between the lateral meniscus tear and the cartilage damage of the lateral compartment. (author)

  19. Localization of lesions in aphasia, (2)

    International Nuclear Information System (INIS)

    Hojo, Kei; Watanabe, Shunzo; Tasaki, Hiroichi; Sato, Tokijiro; Metoki, Hirofumi.

    1985-01-01

    The relationship between the focus and the extent of the lesions and the various symptoms was investigated. 1. Broca aphasics: More than 80% of the group with obvious anarthric components had lesions of the third frontal gyrus involving Broca's area and the lower part of the precental gyrus as well as opercular and insular regions. The size of the lesions of this group was significantly larger than that of the group without marked anarthric components, and the latter was proved to have little localizing value. 2. Wernicke aphasics: The group with poor reading comprehension had cortical and/or subcortical lesions, involving posterior parts of both superior and middle temporal gyri as well as the supramarginal gyrus. On the other hand, lesions of the group with poor auditory comprehension were more anteriorly located and localized in the deep structures. Lesions of the group with poor Token test scores were large and scattered more anteriorly and/or posteriorly compared with those of the group with good Token test scores. 3. Amnestic aphaiscs: The group with poor naming scores had somewhat larger lesions than the group with good naming scores, and the lesions were scattered about the left hemisphere. The finding has proved that both groups had little localizing value. 4. Conduction aphasics: Lesions of the non-fluent type were significantly larger than those of the fluent type and distributed more anteriorly. However, highly involved lesions were located in the supramarginal gyrus and posterior parts of superior and/or middle temporal gyri. 5. Global aphasics: Lesions of the group with good articulation and prosody were observed to distribute more posteriorly in comparison with those of the other global aphasics. (J.P.N.)

  20. In-stent neoatherosclerosis and tissue characteristics of restenotic lesions following implantation of second generation drug-eluting stents in unrestricted coronary lesions: Optical frequency domain imaging study.

    Science.gov (United States)

    Sabbah, Mahmoud; Kadota, Kazushige; El-Eraky, Azza; Kamal, Hanan M; Abdellah, Ahmed-Tageldien; El Hawary, Ahmed

    2017-06-01

    Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and morphological appearance of the restenotic tissue. Utilizing Optical frequency domain imaging, two independent reviewers, retrospectively compared the prevalence of neoatherosclerosis (NA), and the morphological differences, and tissue characteristics of 50 G2-DESs in-stent restenosis (ISR) lesions (35 everolimus-eluting stent [22 cobalt-chromium (CoCr), 13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]) implanted liberally in unrestricted coronary lesions. More than half of the stents were implanted in type C lesions, while 40% of the stents were implanted primarily in lesions with recanalized chronic total occlusion. NA, defined as a neointima formation with the presence of lipids or calcification, was observed in fewer than half (24/50) of all ISR lesions with no significant in-between group differences (41%, 69%, and 40% in CoCr, PtCr, and BES respectively, P = 0.22), nor were there any significant differences in the morphological appearance or tissue characteristics between all G2-DESs subtypes. Acknowledging some limitations, our results may suggest that the prevalence of NA and the morphological appearance of restenotic lesions might not differ when G2-DESs are implanted in unrestricted, rather complex, coronary lesions. © 2017, Wiley Periodicals, Inc.

  1. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  2. Use of Molecular Imaging Markers of Glycolysis, Hypoxia and Proliferation (18F-FDG, 64Cu-ATSM and 18F-FLT) in a Dog with Fibrosarcoma

    DEFF Research Database (Denmark)

    Zornhagen, Kamilla; Clausen, Malene; Hansen, Anders Elias

    2015-01-01

    of cancer patients. A dog with fibrosarcoma was imaged using 18F-FDG, 64Cu-ATSM, and 18F-FLT before, during, and after 10 fractions of 4.5 Gy radiotherapy. Uptake of all tracers decreased during treatment. Fluctuations in 18F-FDG and 18F-FLT PET uptakes and a heterogeneous spatial distribution of the three......Glycolysis, hypoxia, and proliferation are important factors in the tumor microenvironment contributing to treatment-resistant aggressiveness. Imaging these factors using combined functional positron emission tomography and computed tomography can potentially guide diagnosis and management...... tracers were seen. Tracer distributions partially overlapped. It appears that each tracer provides distinct information about tumor heterogeneity and treatment response....

  3. Protection to glycolysis by a combination of 5-hydroxy-L-tryptophan and 2-aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats

    International Nuclear Information System (INIS)

    Basu, S.K.; Srinivasan, M.N.; Chuttani, K.; George, S.

    1992-01-01

    Rate of glycolysis in vivo at different time intervals following 8 Gy[LDsub(100(30)] whole body gamma radiation (WBGR) was evaluated by estimating liver glycogen, blood sugar, serum lactic dehydrogenase (LDH) and lactic acid concentration in adult male Sprague Dawley rats. Within 1 hr of radiation exposure, a significant fall in liver glycogen was observed in rats fed food and water ad libitum. The glycogen content increased after 24 hr and had returned to control level on 7th day after radiation exposure. Blood sugar, serum LDH and blood lactate levels increased significantly as compared to non irradiated controls. Pretreatment with 5-hydroxy-L-tryptophan (5-HTP;100 mg/kg) + 2-aminoethylisothiuronium bromide hydrobromide (AET;20 mg/kg)ip 30 min before 8 Gy WBGR, modified these values and restored them to normal level on 7th day post-irradiation. (author). 24 refs

  4. Frequency of fungal infection in biopsies of oral mucosal lesions: A prospective hospital-based study

    Directory of Open Access Journals (Sweden)

    Thimmarasa Venkappa Bhovi

    2015-01-01

    Full Text Available Aims and Objectives: To determine the frequency and common site of fungal infection in biopsies of oral mucosal lesions and also to detect the lesions most likely to be infected with fungal infection. Materials and Methods: A total of 100 patients with oral mucosal lesions were advised routine hematological examination followed by incisional biopsy under local anesthesia. The specimen were fixed in 10% neutral buffered formalin and processed. One section from the specimen was stained with hematoxylin and eosin staining for histopathological diagnosis of the lesion and a second section was stained with Periodic acid-Schiff (PAS stain for detection of fungal infection. Results: Out of the 100 patients, the most common mucosal lesion encountered was carcinoma (56% followed by lesions with dysplastic changes (28%, benign lesions (9%, squamous papilloma (2% and oral submucous fibrosis (5%. The most common anatomic location affected by the mucosal lesions were buccal mucosa, followed by the tongue, gingiva, maxillary tuberosity and floor of the mouth with values of 73%, 16%, 6%, 4% and 1%, respectively. Squamous papilloma had the highest positive association with fungal infection (100% followed by lesions with dysplastic changes (17.9% and carcinoma (8.9%. The maximum fungal positive association was encountered in the mucosal lesions over the tongue (18.7% followed by the buccal mucosa (12.3%. Conclusion: There is statistically significant association of fungal infection with dysplastic lesions and papilloma with the tongue and buccal mucosa as the most common sites. Hence a PAS stain should be performed whenever epithelial dysplasia on the tongue and buccal mucosa is diagnosed.

  5. Serial lung imaging with /sup 123/I-IMP in localized pulmonary lesions

    Energy Technology Data Exchange (ETDEWEB)

    Nakajo, Masayuki; Shimada, Jurio; Shimozono, Michiko; Uchiyama, Noriaki; Hiraki, Yoshiyuki; Shinohara, Shinji.

    1988-05-01

    /sup 123/I-IMP (N-isopropyl-p-(/sup 123/I)-iodoamphetamine) dynamic (1 frame/min for 25 mins), 30-min and 4-hr static lung imaging was performed in a total of 65 patients with roentgenographic evidence of localized pulmonary lesion (12 with pneumonia, one with lung abscess, 5 with pulmonary tuberculosis, 3 with pneumoconiosis, one with lung fluke disease and 43 with various histological types of primary lung cancer). The findings in 65 of 70 (95 %) lesions in the initial 1 or 2-min dynamic /sup 123/I-IMP images were analogous to those obtained by /sup 99m/Tc-MAA lung perfusion imaging and decreased activity was observed in 68 of 70 (97 %) lesions, suggesting that the initial images mainly reflected the relative distribution of pulmonary arterial blood flow. However, /sup 123/I-IMP accumulated differently according to the pathological conditions afterwards. Decrease activity from /sup 123/I-IMP was contineously observed in a cavity of the lung abscess, 2 of 2 tuberculomas, 3 of 7 large nodules of pneumoconiosis and all of the 42 cancerous lesions which were possible to be evaluated. Gradual increased in activity relative to that of ''normal lung fields'' was observed in all 14 lesions of pneumonia; pneumonic lesions of the lung abscess, tuberculosis and lung fluke disease; 4 of 7 large nodules of pneumoconiosis; all of 8 atelectatic lesions and 32 of 44 areas surrounding cancers (most of them had roentgenographic evidence of infiltrating shadows). Thus /sup 123/I-IMP accumulated increasingly in pneumonic and atelectatic lesions, while it appeared not to accumulate in such lesions replacing lung tissues as cavity, caseous and fibrous lesions and primary lung cancers. /sup 123/I-IMP can be used as a new lung imaging agent to provide diagnostic informations on the property of pulmonary lesions.

  6. Serial lung imaging with 123I-IMP in localized pulmonary lesions

    International Nuclear Information System (INIS)

    Nakajo, Masayuki; Shimada, Jurio; Shimozono, Michiko; Uchiyama, Noriaki; Hiraki, Yoshiyuki; Shinohara, Shinji.

    1988-01-01

    123 I-IMP (N-isopropyl-p-[ 123 I]-iodoamphetamine) dynamic (1 frame/min for 25 mins), 30-min and 4-hr static lung imaging was performed in a total of 65 patients with roentgenographic evidence of localized pulmonary lesion (12 with pneumonia, one with lung abscess, 5 with pulmonary tuberculosis, 3 with pneumoconiosis, one with lung fluke disease and 43 with various histological types of primary lung cancer). The findings in 65 of 70 (95 %) lesions in the initial 1 or 2-min dynamic 123 I-IMP images were analogous to those obtained by 99m Tc-MAA lung perfusion imaging and decreased activity was observed in 68 of 70 (97 %) lesions, suggesting that the initial images mainly reflected the relative distribution of pulmonary arterial blood flow. However, 123 I-IMP accumulated differently according to the pathological conditions afterwards. Decrease activity from 123 I-IMP was contineously observed in a cavity of the lung abscess, 2 of 2 tuberculomas, 3 of 7 large nodules of pneumoconiosis and all of the 42 cancerous lesions which were possible to be evaluated. Gradual increased in activity relative to that of ''normal lung fields'' was observed in all 14 lesions of pneumonia; pneumonic lesions of the lung abscess, tuberculosis and lung fluke disease; 4 of 7 large nodules of pneumoconiosis; all of 8 atelectatic lesions and 32 of 44 areas surrounding cancers (most of them had roentgenographic evidence of infiltrating shadows). Thus 123 I-IMP accumulated increasingly in pneumonic and atelectatic lesions, while it appeared not to accumulate in such lesions replacing lung tissues as cavity, caseous and fibrous lesions and primary lung cancers. 123 I-IMP can be used as a new lung imaging agent to provide diagnostic informations on the property of pulmonary lesions. (author)

  7. Relationship between IL-1β production and endodontic status of human periapical lesions

    Directory of Open Access Journals (Sweden)

    Popovska Lidija

    2017-01-01

    Full Text Available Background/Aim. Apical periodontitis is mainly caused by bacterial infection within the root canal and periapical bone destruction which are prominent features of this lesion. The aim of this study was to determine the quantity of interleukin-1β in the tissues of periapical lesions and to analyze its relationships with: lesion size, previous treatments and pathohistological finding of involved teeth. Methods. Periapical tissues were obtained from patients undergoing periapical surgery. Out of all 80 cases included in the study, 24 had no previous endodontic treatment (open lesions, 37 were with endodontic failure (closed lesion and in 15 cases root canal retreatment was performed few months before the surgery. By excluding four samples, the total of 76 samples, consisted of periapical lesions and the apical part of the tooth root, was collected. Each periapical tissue sample was divided into two equal parts. The one half of each lesion was used for quantification of interleukin-1β in tissue homogenates by the enzyme-linked immunosorbent assay (ELISA method. The other part of each lesion was used for histopathological evaluation. Results. For each of the tissue homogenates, the quantity of interleukin-1β was measured, and it ranged from 0.6 pg/mg up to 74 pg/mg. There was no significant difference between the symptomatology and amount of interleukin-1β. Statistical data analysis showed a moderate correlation between lesion size and interleukin-1β measured values. The highest levels of interleukin-1β corresponded with chronic lesions in the stages of acute exacerbation and granulomas in early developing stages. Persistant granulomas, scar tissues, non-inflamed cysts and teeth with recently finished endodontic treatments showed a significantly lower level of interleukin-1β. Conclusion. The study results suggest that the differences in quantity of interleukin-1β correlate to lesion progression and phases of development.

  8. Pathologic features of lower extremity arterial lesions in diabetes mellitus:an analysis of 162 patients

    International Nuclear Information System (INIS)

    Guo Xiangjiang; Zhang Jiwei

    2010-01-01

    Objective: To investigate the angiographic manifestations of lower extremity atherosclerotic occlusion in patients with diabetes mellitus. Methods: The angiographic findings of lower extremity in 162 patients with diabetes mellitus were retrospectively analyzed. (1) The arteries of lower extremity were divided into the following four segments: iliac, femoral, popliteal and crural artery. The involvements of these arteries were documented. (2) Based on the lesion's number, location, nature (stricture or occlusion) and length ( 5 cm), the diabetic arterial diseases were categorized. Results: (1) Of 162 diabetic lower limbs, multiple segmental lesions were seen in 131, superficial femoral arterial lesions in 130, and crural arterial lesions in 139, of which 130 arterial lesions had at least two below-the-knee arteries being involved. (2) Based on segmental angiographic classification, a total of 660 vascular lesions were detected, including stricture lesions (33.8%) and occlusive lesions (66.2%). Of the 437 occlusions, 70.5% were located in below-the-knee arteries, and most of which were longer than 10 cm and located in anterior and posterior tibial arteries, while only a few peroneal arteries were involved (P < 0.0001). One hundred and fifty-two lesions were detected in superficial femoral arteries, of which 49 (31.2%) were located at the origin of the superficial femoral artery and 56 (35.7) were in the adductor canal hiatus. Conclusion: The main feature of peripheral arterial disease of lower extremity caused by diabetes mellitus is multi-level atherosclerotic occlusion, the superficial femoral and the crural arteries are most likely to be involved. The lesions of superficial femoral artery are often located at the arterial origin and in the adductor canal hiatus, while the deep femoral artery and the femoral artery are less involved. Long occlusive lesions are more prevalent in crural arteries, especially in anterior and posterior tibial arteries. (J Intervent

  9. Differentiation of thyroid lesion detected by FDG PET/CT using SUV ratio

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bom Sahn; Kang, Won Jun; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We investigated the usefulness of SUV ratio to discriminate focal thyroid lesion incidentally detected on 18F-FDG PET/CT (FDG PET) in patients with malignant disease. A total of 2167 subjects with malignant tumor underwent PET/CT for staging. Forty-five of 2167 subjects (2.1%) showed hypermetabolic thyroid lesions on FDG PET. Of 45, 21 lesions were confirmed by pathology (n = 16) or follow up exam (n=5). Seventeen patients had focal FDG uptakes, while 4 patients had diffuse thyroid uptakes. Standardized uptake value (SUV) was measured by drawing region of interest (ROI) on bilateral thyroid lobes and liver. From 21 patients, 12 thyroid lesions were confirmed as malignant lesions and 9 lesions as benign lesions. All of bilateral thyroid FDG uptakes were determined as benign disease such as thyroiditis. From seventeen focal thyroid incidentaloma, FDG PET had 100 % (12/12) of sensitivity and 60 % (3/5) of specificity, retrospectively. Malignant nodules had a significantly higher lesion to liver ratio than those of benign nodules (2.10.9 vs. 1.20.6, p=0.029). With ROC curve, the best cut-off value of lesion to liver was 1.0 with sensitivity of 100% and specificity of 60 % (area under the curve=0.783). The SUV ratio of lesion to contralateral lobe do not have statistical significance to determine malignancy (3.72.1 vs. 2.61.7, p=0.079). This study showed that focal thyroidal FDG uptake detected by FDG PET could be differentiated with best performance by SUV ratio of lesion to liver.

  10. The Phosphatidylinositol 3,5-Bisphosphate (PI(3,5)P2)-dependent Tup1 Conversion (PIPTC) Regulates Metabolic Reprogramming from Glycolysis to Gluconeogenesis*

    Science.gov (United States)

    Han, Bong-Kwan; Emr, Scott D.

    2013-01-01

    Glucose/carbon metabolism is a fundamental cellular process in living cells. In response to varying environments, eukaryotic cells reprogram their glucose/carbon metabolism between aerobic or anaerobic glycolysis, oxidative phosphorylation, and/or gluconeogenesis. The distinct type of glucose/carbon metabolism that a cell carries out has significant effects on the cell's proliferation and differentiation. However, it is poorly understood how the reprogramming of glucose/carbon metabolism is regulated. Here, we report a novel endosomal PI(3,5)P2 lipid-dependent regulatory mechanism that is required for metabolic reprogramming from glycolysis to gluconeogenesis in Saccharomyces cerevisiae. Certain gluconeogenesis genes, such as FBP1 (encoding fructose-1,6-bisphosphatase 1) and ICL1 (encoding isocitrate lyase 1) are under control of the Mig1 repressor and Cyc8-Tup1 corepressor complex. We previously identified the PI(3,5)P2-dependent Tup1 conversion (PIPTC), a mechanism to convert Cyc8-Tup1 corepressor to Cti6-Cyc8-Tup1 coactivator. We demonstrate that the PIPTC plays a critical role for transcriptional activation of FBP1 and ICL1. Furthermore, without the PIPTC, the Cat8 and Sip4 transcriptional activators cannot be efficiently recruited to the promoters of FBP1 and ICL1, suggesting a key role for the PIPTC in remodulating the chromatin architecture at the promoters. Our findings expand our understanding of the regulatory mechanisms for metabolic reprogramming in eukaryotes to include key regulation steps outside the nucleus. Given that Tup1 and the metabolic enzymes that control PI(3,5)P2 are highly conserved among eukaryotes, our findings may provide important insights toward understanding glucose/carbon metabolic reprogramming in other eukaryotes, including humans. PMID:23733183

  11. The phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)-dependent Tup1 conversion (PIPTC) regulates metabolic reprogramming from glycolysis to gluconeogenesis.

    Science.gov (United States)

    Han, Bong-Kwan; Emr, Scott D

    2013-07-12

    Glucose/carbon metabolism is a fundamental cellular process in living cells. In response to varying environments, eukaryotic cells reprogram their glucose/carbon metabolism between aerobic or anaerobic glycolysis, oxidative phosphorylation, and/or gluconeogenesis. The distinct type of glucose/carbon metabolism that a cell carries out has significant effects on the cell's proliferation and differentiation. However, it is poorly understood how the reprogramming of glucose/carbon metabolism is regulated. Here, we report a novel endosomal PI(3,5)P2 lipid-dependent regulatory mechanism that is required for metabolic reprogramming from glycolysis to gluconeogenesis in Saccharomyces cerevisiae. Certain gluconeogenesis genes, such as FBP1 (encoding fructose-1,6-bisphosphatase 1) and ICL1 (encoding isocitrate lyase 1) are under control of the Mig1 repressor and Cyc8-Tup1 corepressor complex. We previously identified the PI(3,5)P2-dependent Tup1 conversion (PIPTC), a mechanism to convert Cyc8-Tup1 corepressor to Cti6-Cyc8-Tup1 coactivator. We demonstrate that the PIPTC plays a critical role for transcriptional activation of FBP1 and ICL1. Furthermore, without the PIPTC, the Cat8 and Sip4 transcriptional activators cannot be efficiently recruited to the promoters of FBP1 and ICL1, suggesting a key role for the PIPTC in remodulating the chromatin architecture at the promoters. Our findings expand our understanding of the regulatory mechanisms for metabolic reprogramming in eukaryotes to include key regulation steps outside the nucleus. Given that Tup1 and the metabolic enzymes that control PI(3,5)P2 are highly conserved among eukaryotes, our findings may provide important insights toward understanding glucose/carbon metabolic reprogramming in other eukaryotes, including humans.

  12. Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer

    Directory of Open Access Journals (Sweden)

    Ling Li

    2015-04-01

    Full Text Available Inhibition of glycolysis using 2-deoxy-d-glucose (2DG, 20 mM, 24–48 h combined with inhibition of the pentose cycle using dehydroepiandrosterone (DHEA, 300 µM, 24–48 h increased clonogenic cell killing in both human prostate (PC-3 and DU145 and human breast (MDA-MB231 cancer cells via a mechanism involving thiol-mediated oxidative stress. Surprisingly, when 2DG+DHEA treatment was combined with an inhibitor of glutathione (GSH synthesis (l-buthionine sulfoximine; BSO, 1 mM that depleted GSH>90% of control, no further increase in cell killing was observed during 48 h exposures. In contrast, when an inhibitor of thioredoxin reductase (TrxR activity (Auranofin; Au, 1 µM, was combined with 2DG+DHEA or DHEA-alone for 24 h, clonogenic cell killing was significantly increased in all three human cancer cell lines. Furthermore, enhanced clonogenic cell killing seen with the combination of DHEA+Au was nearly completely inhibited using the thiol antioxidant, N-acetylcysteine (NAC, 20 mM. Redox Western blot analysis of PC-3 cells also supported the conclusion that thioredoxin-1 (Trx-1 oxidation was enhanced by treatment DHEA+Au and inhibited by NAC. Importantly, normal human mammary epithelial cells (HMEC were not as sensitive to 2DG, DHEA, and Au combinations as their cancer cell counterparts (MDA-MB-231. Overall, these results support the hypothesis that inhibition of glycolysis and pentose cycle activity, combined with inhibition of Trx metabolism, may provide a promising strategy for selectively sensitizing human cancer cells to oxidative stress-induced cell killing.

  13. Soluble Sugars as the Carbohydrate Reserve for CAM in Pineapple Leaves : Implications for the Role of Pyrophosphate:6-Phosphofructokinase in Glycolysis.

    Science.gov (United States)

    Carnal, N W; Black, C C

    1989-05-01

    Neutral ethanol-soluble sugar pools serve as carbohydrate reserves for Crassulacean acid metabolism (CAM) in pineapple (Ananas comosus (L.) Merr.) leaves. Levels of neutral soluble sugars and glucans fluctuated reciprocally with concentrations of malic acid. Hexose loss from neutral soluble-sugar pools was sufficient to account for malic acid accumulation with about 95% of the required hexose accounted for by turnover of fructose and glucose pools. Hexose loss from starch or starch plus lower molecular weight glucan pools was insufficient to account for nocturnal accumulation of malic acid. The apparent maximum catalytic capacity of pyrophosphate:6-phosphofructokinase (PPi-PFK) at 15 degrees C was about 16 times higher than the mean maximum rate of glycolysis that occurred to support malic acid accumulation in pineapple leaves at night and 12 times higher than the mean maximum rate of hexose turnover from all carbohydrate pools. The apparent maximum catalytic capacity of ATP-PFK at 15 degrees C was about 70% of the activity required to account for the mean maximal rate of hexose turnover from all carbohydrate pools if turnover were completely via glycolysis, and marginally sufficient to account for mean maximal rates of acidification. Therefore, at low night temperatures conducive to CAM and under subsaturating substrate concentrations, PPi-PFK activity, but not ATP-PFK activity, would be sufficient to support the rate of glycolytic carbohydrate processing required for acid accumulation. These data for pineapple establish that there are at least two types of CAM plants with respect to the nature of the carbohydrate reserve utilized to support nighttime CO(2) accumulation. The data further indicate that the glycolytic carbohydrate processing that supports acidification proceeds in different subcellular compartments in plants utilizing different carbohydrate reserves.

  14. [Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions].

    Science.gov (United States)

    Geier, T; Glende, M; Reich, J G

    1978-01-01

    In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.

  15. Traumatic brain lesions in newborns

    Directory of Open Access Journals (Sweden)

    Nícollas Nunes Rabelo

    Full Text Available ABSTRACT The neonatal period is a highly vulnerable time for an infant. The high neonatal morbidity and mortality rates attest to the fragility of life during this period. The incidence of birth trauma is 0.8%, varying from 0.2-2 per 1,000 births. The aim of this study is to describe brain traumas, and their mechanism, anatomy considerations, and physiopathology of the newborn traumatic brain injury. Methods A literature review using the PubMed data base, MEDLINE, EMBASE, Science Direct, The Cochrane Database, Google Scholar, and clinical trials. Selected papers from 1922 to 2016 were studied. We selected 109 papers, through key-words, with inclusion and exclusion criteria. Discussion This paper discusses the risk factors for birth trauma, the anatomy of the occipito-anterior and vertex presentation, and traumatic brain lesions. Conclusion Birth-related traumatic brain injury may cause serious complications in newborn infants. Its successful management includes special training, teamwork, and an individual approach.

  16. Red Blood Cell Storage Lesion

    Directory of Open Access Journals (Sweden)

    Daryl J. Kor

    2009-10-01

    Full Text Available The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L, lysophosphatidylcholine (lyso-PC, and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.

  17. Cerebral CT of ischaemic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Aulich, A

    1981-11-25

    The diagnosis of stroke must first be established by clinical examination. CT has proved useful for confirmation of the diagnosis and provides a global intracranial picture of morphological changes in cerebral vascular diseases. A hemorrhage can be recognized with certainty at the first CT examination as the cause of the stroke, but in the detection of a lesion due to ischemia an important role is played by the correct choice of the time of examination, and in some cases also of the check-up with contrast medium. The differential diagnosis between infarct in the acute stage and encephalitis or gliomas of low-grade malignity can be difficult. A decision can often only be made after a series of examinations. Postmalacial conditions are often difficult to differentiate from defects due to other causes, such as hemorrhage, head injury, postoperative states and after encephalitis. A knowledge of the anamnesis and the clinical findings is indispensable for CT evaluation. In assessing the prognosis before vascular surgery on the extracranial brain-supplying vessels the performance of a CT examination should be advised. A warning is given against the use of CT as a screening method.

  18. Total Quality Leadership

    Science.gov (United States)

    1991-01-01

    More than 750 NASA, government, contractor, and academic representatives attended the Seventh Annual NASA/Contractors Conference on Quality and Productivity. The panel presentations and Keynote speeches revolving around the theme of total quality leadership provided a solid base of understanding of the importance, benefits, and principles of total quality management (TQM). The presentations from the conference are summarized.

  19. Genoptraening efter total knaealloplastik

    DEFF Research Database (Denmark)

    Holm, Bente; Kehlet, Henrik

    2009-01-01

    The short- and long-term benefits of post-discharge physiotherapy regimens after total knee arthroplasty are debatable. A national survey including hospitals in Denmark that perform total knee arthroplasty showed a large variability in indication and regimen for post-knee arthroplasty...

  20. Malignant Lesions as Mammographically Appearing Intramammary Ganglia

    International Nuclear Information System (INIS)

    Martinez-Miraveta, P.; Pons, M. J.; Pina, L. J.; Zornoza, G.

    2004-01-01

    Intramammary ganglia are frequent mammographic findings of no pathological importance. We present two cases of malignant breast lesions whose mammographic appearance could resemble that of intramammary ganglia. Although the mammographic appearance of a lesion is similar to that of intramammary ganglia, it should be carefully studied, especially if it presents a poorly defined border or is palpable. (Author)

  1. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...

    African Journals Online (AJOL)

    Contact allergic reactions due to hypersensitivity to dental materials in professionals and ... Keywords: Amalgam, Amalgam contact hypersensitivity lesion, Lichenoid reaction, Oral mucosa ... was associated with mild burning sensation. The patient did ... OLLD in which oral and/or skin lesions appear in temporal association ...

  2. Oncocytic lesions of the ophthalmic region

    DEFF Research Database (Denmark)

    Østergaard, Jens; Prause, Jan U; Heegaard, Steffen

    2011-01-01

    –brown, cystic and slow-growing. The antimitochondrial antibody MU213-UC produced a distinct and intense immunostaining of all oncocytic lesions and was found to be useful in substantiating oncocytic differentiation. Twenty-six of the lesions originated in the caruncle, three in the conjunctiva, two...

  3. Principal component analysis of psoriasis lesions images

    DEFF Research Database (Denmark)

    Maletti, Gabriela Mariel; Ersbøll, Bjarne Kjær

    2003-01-01

    A set of RGB images of psoriasis lesions is used. By visual examination of these images, there seem to be no common pattern that could be used to find and align the lesions within and between sessions. It is expected that the principal components of the original images could be useful during future...

  4. Imaging granulomatous lesions with optical coherence tomography

    DEFF Research Database (Denmark)

    Banzhaf, Christina; Jemec, Gregor B E

    2012-01-01

    To investigate and compare the presentation of granulomatous lesions in optical coherence tomography (OCT) images and compare this to previous studies of nonmelanoma skin tumors.......To investigate and compare the presentation of granulomatous lesions in optical coherence tomography (OCT) images and compare this to previous studies of nonmelanoma skin tumors....

  5. The Post-Ureteroscopic Lesion Scale (PULS)

    DEFF Research Database (Denmark)

    Schoenthaler, Martin; Buchholz, Noor; Farin, Erik

    2014-01-01

    The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading system for the description of ureteral lesions after ureteroscopy. In this article, we present the results of a video-based multicenter evaluation of the inter-rater reliability of clinically important PULS grades 0-3....

  6. Hypervascular liver lesions in radiologically normal liver

    Energy Technology Data Exchange (ETDEWEB)

    Amico, Enio Campos; Alves, Jose Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; Joao, Samir Assi; Liguori, Adriano de Araujo Lima, E-mail: ecamic@uol.com.br [Hospital Universitario Onofre Lopes (HUOL/UFRN), Natal, RN (Brazil). Clinica Gastrocentro e Ambulatorios de Cirurgia do Aparelho Digestivo e de Cirurgia Hepatobiliopancreatica

    2017-09-01

    Background: The hypervascular liver lesions represent a diagnostic challenge. Aim: To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. Method: This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Results: Eighty eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p< 0.001), personal history of cancer (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. Conclusion: It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine amino transaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. (author)

  7. Radiotherapy for ocular lesions by electron beam therapy

    International Nuclear Information System (INIS)

    Miyaishi, Kazuo

    1981-01-01

    Radiotherapy can be very significant as the treatment for ocular lesions, eyes need to be preserved as properly as possible on their functions and cosmetics. The appliance of conventional X ray therapy has been gradually abandaned as conventional X ray therapy ceased to be accepted as the general treatment for malignant tumors. Consequently the necessity of electron beam therapy has been rising even as the substituted method for conventional X ray therapy. The department of radiology of Gunma University was obliged to establish a new therapy for ocular lesions, and has been trying electron beam therapy since 1973; It is concluded that electron beam therapy is not at all inferior to conventional X ray therapy as reported above. Basic therapeutic methods for ocular lesions are the following: 1) For epidermoid carcinoma, 600 rads at a time, 3600 - 4200 rads in total is applied by 8 MeV electron twice a week method. 2) For malignant melanoma, 1000 rads at a time, 4000 - 5000 rads in total is applied by 8 MeV electron twice a week method. 3) For orbitar lymphoid neoplasm, Cobalt-60 γ ray or Linac X ray is applied together with electron beam. 4) For embryonal rhabdomyosarcoma, adenoid cystic cancer etc., the therapy for whole body is necessary. 5) For benign tumors, a small dose at a time is applied for a long time. (author)

  8. Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex

    International Nuclear Information System (INIS)

    Boronat, Susana; Barber, Ignasi; Pargaonkar, Vivek; Chang, Joshua; Thiele, Elizabeth A.

    2016-01-01

    Sclerotic bone lesions are often seen on chest CT in adults with tuberous sclerosis complex. To characterize bone lesions at abdominal MRI in children with tuberous sclerosis complex. This retrospective review included 70 children with tuberous sclerosis complex who had undergone abdominal MRI for renal imaging. An additional longitudinal study was performed in 50 children who had had two or more MRI scans. Abdominal CT (eight children) and radiographs (three children) were reviewed and compared with MRI. A total of 173 sclerotic bone lesions were detected in 51/70 children (73%; 95% confidence interval: 0.61-0.82) chiefly affecting vertebral pedicles. New lesions appeared in 20 children and growth of previous sclerotic bone lesions was documented in 14 children. Sclerotic bone lesions were more frequent in girls and in children with more extensive renal involvement. Sclerotic bone lesions are commonly detected by abdominal MRI in children with tuberous sclerosis complex. They usually affect posterior vertebral elements and their number and size increase with age. As current recommendations for tuberous sclerosis complex surveillance include renal MR performed in childhood, recognition of these lesions is useful. (orig.)

  9. Comparison of AMI-25 enhanced MRI and helical dynamic CT in the detection of hepatic lesions

    International Nuclear Information System (INIS)

    Saitou, Kazuhiro; Matsuda, Hiromichi; Fukushima, Hiroaki; Kanzaki, Hiroshi; Hirose, Takashi; Karizaki, Dai; Abe, Kimihiko; Amino, Saburou

    1994-01-01

    We performed AMI-25 enhanced MRI and helical dynamic CT in 12 cases of hepatic lesions. Nine of these were hepatocellular carcinomas. Two cases were metastatic liver tumors (the primary lesion was gastric in one and the other was gallbladder cancer). One case was suspected to be adenomatous hyperplasia. Thirty-two lesions were detected in T2-weighted SE images before AMI-25 administration, while 46 lesions were detected in AMI-25 enhanced MRI images. In particular, AMI-25 enhanced MRI was superior to plain MRI in lesions less than 10 mm in size. A total of 48 lesions were detected in helical dynamic CT. Although AMI-25 enhanced MRI almost equaled helical dynamic CT in the detection of liver tumors, helical dynamic CT was slightly superior to AMI-25 enhanced MRI in the detection of subphrenic lesions. It was possible to know the hemodynamics in each hepatic lesion by helical dynamic CT. AMI-25 enhanced MRI was useful to know the inclusion of reticuloendothelial system, and that yielded different diagnoses in adenomatous hyperplasia and well differentiated hepatocellular carcinoma. Helical dynamic CT was useful for qualitative diagnosis. Both AMI-25 enhanced MRI and helical dynamic CT contributed to the detection of liver tumor and qualitative diagnosis. (author)

  10. Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex

    Energy Technology Data Exchange (ETDEWEB)

    Boronat, Susana [Massachusetts General Hospital, Department of Neurology, Boston, MA (United States); Universitat Autonoma de Barcelona, Department of Pediatric Neurology, Vall d' Hebron Hospital, Barcelona (Spain); Barber, Ignasi [Universitat Autonoma de Barcelona, Department of Pediatric Radiology, Vall d' Hebron Hospital, Barcelona (Spain); Pargaonkar, Vivek [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Chang, Joshua; Thiele, Elizabeth A. [Massachusetts General Hospital, Department of Neurology, Boston, MA (United States)

    2016-05-15

    Sclerotic bone lesions are often seen on chest CT in adults with tuberous sclerosis complex. To characterize bone lesions at abdominal MRI in children with tuberous sclerosis complex. This retrospective review included 70 children with tuberous sclerosis complex who had undergone abdominal MRI for renal imaging. An additional longitudinal study was performed in 50 children who had had two or more MRI scans. Abdominal CT (eight children) and radiographs (three children) were reviewed and compared with MRI. A total of 173 sclerotic bone lesions were detected in 51/70 children (73%; 95% confidence interval: 0.61-0.82) chiefly affecting vertebral pedicles. New lesions appeared in 20 children and growth of previous sclerotic bone lesions was documented in 14 children. Sclerotic bone lesions were more frequent in girls and in children with more extensive renal involvement. Sclerotic bone lesions are commonly detected by abdominal MRI in children with tuberous sclerosis complex. They usually affect posterior vertebral elements and their number and size increase with age. As current recommendations for tuberous sclerosis complex surveillance include renal MR performed in childhood, recognition of these lesions is useful. (orig.)

  11. Depiction and characterization of liver lesions in whole body [18F]-FDG PET/MRI

    International Nuclear Information System (INIS)

    Beiderwellen, Karsten; Gomez, Benedikt; Buchbender, Christian; Hartung, Verena; Poeppel, Thorsten D.; Nensa, Felix; Kuehl, Hilmar; Bockisch, Andreas; Lauenstein, Thomas C.

    2013-01-01

    Objectives: To assess the value of PET/MRI with [ 18 F]-FDG using a whole body protocol for the depiction and characterization of liver lesions in comparison to PET/CT. Methods: 70 patients (31 women, 39 men) with solid tumors underwent [ 18 F]-FDG PET/CT and followed by an additional PET/MRI using an integrated scanner. Two readers rated the datasets (PET/CT; PET/MRI) regarding conspicuity of hepatic lesions (4-point ordinal scale) and diagnostic confidence (5-point ordinal scale). Median scores for lesion conspicuity and diagnostic confidence were compared using Wilcoxon's rank sum test. Prior examinations, histopathology and clinical follow-up (116 ± 54 days) served as standard of reference. Results: 36 of 70 (51%) patients showed liver lesions. Using PET/CT and PET/MRI all patients with liver metastases could correctly be identified. A total of 97 lesions were found (malignant n = 26; benign n = 71). For lesion conspicuity significantly higher scores were obtained for PET/MRI in comparison to PET/CT (p < 0.001). Significantly better performance for diagnostic confidence was observed in PET/MRI, both for malignant as for benign lesions (p < 0.001). Conclusions: PET/MRI, even in the setting of a whole body approach, provides higher lesion conspicuity and diagnostic confidence compared to PET/CT and may therefore evolve as an attractive alternative in oncologic imaging

  12. [Microsurgery assisted by intraoperative magnetic resonance imaging and neuronavigation for small lesions in deep brain].

    Science.gov (United States)

    Song, Zhi-jun; Chen, Xiao-lei; Xu, Bai-nan; Sun, Zheng-hui; Sun, Guo-chen; Zhao, Yan; Wang, Fei; Wang, Yu-bo; Zhou, Ding-biao

    2012-01-03

    To explore the practicability of resecting small lesions in deep brain by intraoperative magnetic resonance imaging (iMRI) and neuronavigator-assisted microsurgery and its clinical efficacies. A total of 42 cases with small lesions in deep brain underwent intraoperative MRI and neuronavigator-assisted microsurgery. The drifting of neuronavigation was corrected by images acquired from intraoperative MR rescanning. All lesions were successfully identified and 40 cases totally removed without mortality. Only 3 cases developed new neurological deficits post-operatively while 2 of them returned to normal neurological functions after a follow-up duration of 3 months to 2 years. The application of intraoperative MRI can effectively correct the drifting of neuronavigation and enhance the accuracy of microsurgical neuronavigation for small lesions in deep brain.

  13. Inhibition of glycolysis and growth of colon cancer cells by 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO in combination with butyrate, 2-deoxy glucose, 3-bromopyruvate or biguanides

    Directory of Open Access Journals (Sweden)

    Lea MA

    2015-09-01

    Full Text Available Introduction: Glycolysis shows a positive correlation with growth of human colon cancer cells. PFKFB3 is an important enzyme regulating glycolysis in many tumor cells and presents a target for cancer chemotherapy. We studied the action of an inhibitor of PFKFB3, 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO, as a single agent and in combination with other molecules that affect glycolysis. Materials and methods: Effects on growth were studied in four human colon cancer cell lines. Glucose metabolism was monitored by uptake from the incubation medium and lactic acid production was judged by acidification of the medium. Induction of alkaline phosphatase served as a marker of differentiation. Results: Growth of colon cancer cells was inhibited by 3PO and butyrate but only butyrate induced activation of alkaline phosphatase. Although metformin and phenformin can increase glucose metabolism, they inhibit colon cancer cell growth and can exert additive inhibitory effects in combination with 3PO. Additive growth inhibitory effects with 3PO were also observed with two compounds that inhibit glycolysis: 2-deoxyglucose and 3-bromopyruvate. Conclusion: 3PO was an inhibitor of growth of colon cancer cells and may be a useful agent in combination with other drugs that inhibit colon cancer cell proliferation.

  14. The relevance of clinical and radiographic features of jaw lesions: A prospective study

    Directory of Open Access Journals (Sweden)

    Juliane Piragine ARAUJO

    Full Text Available Abstract The study was carried out in a Brazilian population and the aim was to describe the prevalence and the clinic-radiographical features of jaw lesions. In addition, a comparison between the main diagnosis hypothesis and final diagnosis was accessed. A prospective study which evaluated all patients with jaw lesions diagnosed in an Oral Diagnosis Center, between August 2013 and October 2014. A total of 450 patients were observed for the first time, and 130 had some type of jaw lesion. The mean age of the patients was 35.2 years ± 17.86. Among these, 71 were women (54.62% and 87 were Caucasian (66.92%. The mandible was affected more frequently (71.43% than the maxilla (28.57%. Swelling and pain were the most frequent clinical signs and symptoms and were observed in 60 (42.85% and 38 (27.14% cases, respectively. The panoramic x-ray was the main radiographic exam utilized (88.57%. Radiolucent lesions accounted for 89 cases (63.57% and the unilocular form was present in 114 cases (81.43%. A total of 93 cases had histopathological analyses and the periapical cyst was the most frequent lesion. In the other 47 lesions, the diagnosis was conducted by clinical and radiographic management. Bone lesions were frequent, being noted on first visit in approximately 30% of patients; in 1/3 of the cases, the diagnoses were completed with a combination of clinical and radiographic exams.

  15. Heterotopic bone formation following total shoulder arthroplasty

    DEFF Research Database (Denmark)

    Kjaersgaard-Andersen, P.; Frich, Lars Henrik; Sjøbjerg, J.O.

    1989-01-01

    The incidence and location of heterotopic bone formation following total shoulder arthroplasty were evaluated in 58 Neer Mark-II total shoulder replacements. One year after surgery, 45% had developed some ectopic ossification. In six shoulders (10%) the ossifications roentgenographically bridged...... the glenohumeral and/or the glenoacromial space. There was no correlation between shoulder pain and the development of ossification. Shoulders with grade III heterotopic bone formation had a limited range of active elevation compared with shoulders without or with only a milder lesion. Men and patients...... with osteoarthritis of the shoulder joint were significantly disposed to the development of heterotopic bone. Heterotopic bone formation following total shoulder arthroplasty is frequent, but disabling heterotopic ossifications seem to be rare....

  16. Identification of total reversible cysteine oxidation in an atherosclerosis model using a modified biotin switch assay.

    Science.gov (United States)

    Li, Ru; Huang, Jiqing; Kast, Juergen

    2015-05-01

    Oxidative stress due to the imbalance of reactive oxygen species (ROS) and the resulting reversible cysteine oxidation (CysOX) are involved in the early proatherogenic aspect of atherosclerosis. Given that the corresponding redox signaling pathways are still unclear, a modified biotin switch assay was developed to quantify the reversible CysOX in an atherosclerosis model established by using a monocytic cell line treated with platelet releasate. The accumulation of ROS was observed in the model system and validated in human primary monocytes. Through the application of the modified biotin switch assay, we obtained the first reversible CysOX proteome for this model. A total of 75 peptides, corresponding to 53 proteins, were quantified with oxidative modification. The bioinformatics analysis of these CysOX-containing proteins highlighted biological processes including glycolysis, cytoskeleton arrangement, and redox regulation. Moreover, the reversible oxidation of three glycolysis enzymes was observed using this method, and the regulation influence was verified by an enzyme activity assay. NADPH oxidase (NOX) inhibition treatment, in conjunction with the modified biotin switch method, was used to evaluate the global CysOX status. In conclusion, this versatile modified biotin switch assay provides an approach for the quantification of all reversible CysOX and for the study of redox signaling in atherosclerosis as well as in diseases in other biological systems.

  17. Pediatric Awake Craniotomy for Brain Lesions.

    Science.gov (United States)

    Akay, Ali; Rükşen, Mete; Çetin, H Yurday; Seval, H Özer; İşlekel, Sertaç

    2016-01-01

    Awake craniotomy is a special method to prevent motor deficits during the resection of lesions that are located in, or close to, functional areas. Although it is more commonly performed in adult patients, reports of pediatric cases undergoing awake craniotomy are limited in the literature. In our clinic, where we frequently use awake craniotomy in adult patients, we performed this method in 2 selected pediatric cases for lesion surgery. At an early age, these 2 cases diagnosed with epilepsy presented cerebral lesions, but since the lesions enclosed functional areas, surgical resection was not regarded as a treatment option at this time. In these 2 pediatric cases, we successfully completed lesion surgery with awake craniotomy. The method and the techniques employed during surgery are presented concomitant with other reports in the literature. © 2016 S. Karger AG, Basel.

  18. Bone scintigraphy in lesions of the skull

    International Nuclear Information System (INIS)

    Fischer, M.; Wasilewski, A.; Deitmer, T.

    1982-01-01

    The value of 3-phase-scintigraphy in bone lesions of the skull with a new seeking agent 99mTc-2,3-dicarboxypropane-1,1-diphosphonic acid (DPD) is studied. A high soft tissue-bone-ratio of DPD is emphasized. For this reason DPD is used for bone scintigraphy of the skull, because the mass of soft tissue in relation to bone is high and a higher clearance improves the interpretation of the images of the first two phases. An increased tracer uptake is found for skeletal neoplasms (malignant and benign lesions) and for acute osteomyelitis. By contrast, the chronic inflammatory bone lesions showed normal tracer uptake. This new bone seeking agent allows to localize and differentiate tumorous or acute inflammatory lesions and chronic inflammatory bone lesions of the skull

  19. Significance of localization of nonpalpable breast lesions

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ki Keun; Choi, Hyun Ju [Yongdong Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1990-12-15

    As mammography has become more popular for the evaluation of breast symptoms and for the screening of asymptomatic women, the smaller lesions are being detected before they become palpable, therefore preoperative localization became necessary. This has led to the development of several methods for preoperative localization of nonpalpable lesions. Authors analyzed 50 cases with preoperative localization in 45 patients which had abnormal findings on film mammogram or ultrasonomammogram since October 1985 through March 1990 at Yongdong Severance Hospital, College of Medicine, Yonsei University. The results were as follows: 1. Techniques of localization were spot method in 8 cases, conventional needle localization method in 38 cases and Kopan's needle localization method in 4 cases. 2. The most common mammographic indication for localization was focal calcifications in 29 cases(58%), which was followed by a newly developed mass in 25 cases(50%). 3. Outcome of pathologically confirmed diagnosis put into benign lesions in 37 cases(74%) and malignant lesions in 13 cases(26%). 4. Among the cases with localization of lesions which has suggested as benign lesions in film and ultrasonomammogram,all cases(100%) were confirmed in benign lesions pathologically. Among the cases with localization of lesions which has suggested as malignant lesions in film and ultrasonomammogram, pathologic malignant has been proved of 44% and possible histopathologic precursor of malignant was resulted in 25% such as atypical hyperplasia and adenosis. Conclusively, authors consider that the abnormal areas should be removed in their entirety with the sacrifice of minimum volume of contiguous normal breast tissue through the preoperative localization, hence our preoperative localization has contributed favorable prognosis based on material lesions in early stage breast cancer.

  20. Significance of localization of nonpalpable breast lesions

    International Nuclear Information System (INIS)

    Oh, Ki Keun; Choi, Hyun Ju

    1990-01-01

    As mammography has become more popular for the evaluation of breast symptoms and for the screening of asymptomatic women, the smaller lesions are being detected before they become palpable, therefore preoperative localization became necessary. This has led to the development of several methods for preoperative localization of nonpalpable lesions. Authors analyzed 50 cases with preoperative localization in 45 patients which had abnormal findings on film mammogram or ultrasonomammogram since October 1985 through March 1990 at Yongdong Severance Hospital, College of Medicine, Yonsei University. The results were as follows: 1. Techniques of localization were spot method in 8 cases, conventional needle localization method in 38 cases and Kopan's needle localization method in 4 cases. 2. The most common mammographic indication for localization was focal calcifications in 29 cases(58%), which was followed by a newly developed mass in 25 cases(50%). 3. Outcome of pathologically confirmed diagnosis put into benign lesions in 37 cases(74%) and malignant lesions in 13 cases(26%). 4. Among the cases with localization of lesions which has suggested as benign lesions in film and ultrasonomammogram,all cases(100%) were confirmed in benign lesions pathologically. Among the cases with localization of lesions which has suggested as malignant lesions in film and ultrasonomammogram, pathologic malignant has been proved of 44% and possible histopathologic precursor of malignant was resulted in 25% such as atypical hyperplasia and adenosis. Conclusively, authors consider that the abnormal areas should be removed in their entirety with the sacrifice of minimum volume of contiguous normal breast tissue through the preoperative localization, hence our preoperative localization has contributed favorable prognosis based on material lesions in early stage breast cancer

  1. Inducible DNA-repair systems in yeast: competition for lesions.

    Science.gov (United States)

    Mitchel, R E; Morrison, D P

    1987-03-01

    DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate

  2. BENIGN LESIONS OF LARYNX - A CLINICAL STUDY OF 50 CASES

    Directory of Open Access Journals (Sweden)

    Sridhar Reddy

    2016-01-01

    Full Text Available INTRODUCTION Benign Lesions of Larynx (BLL have been defined as “An abnormal mass of tissue in larynx, the growth of which exceeds and is coordinated with that of normal tissue and persists in the same excessive manner after cessation of stimuli which evoked the change.” These lesions have significant influence on vocal, social and emotional adjustments of patients. These patients present with hoarseness of voice. AIM A clinical study was undertaken at Govt. ENT Hospital, Hyderabad, for 1 year from January 2014 to December 2014. Aim of this study was to analyze age and sex distribution, symptomatology, sites of involvement, management and recurrence of benign lesions of larynx. MATERIAL AND METHODS A total of 50 patients were studied who were admitted in the hospital. Inclusion criteria: Patients with Hoarseness of Voice (HOV /change of voice, difficulty in breathing and swallowing, vocal fatigue, Foreign Body (FB sensation in the throat. Exclusion criteria: Malignancy of larynx and acute inflammatory conditions of larynx. RESULTS Benign lesions of larynx show male preponderance with M:F ratio of 2.12:1, with common age group between 31 to 40 years. Chronic vocal misuse was the predominant cause and more in professional voice users. The common lesion was Vocal Cord (VC polyp, followed by VC nodules and papillomas. Common side involved was right side. Majority of the patients had to undergo surgery. Majority of recurrence was seen in laryngeal papillomas (33.33%. CONCLUSION Benign lesions of larynx produce symptoms which vary from mild HOV to life threatening stridor. Early diagnosis leads to effective management. Males were more affected and maximum cases seen between 31 to 40 years. Chronic voice abuse, smoking, alcohol, frequent throat clearing and Laryngopharyngeal Reflux (LPR/Gastroesophageal Reflux Disease (GERD are precipitating factors. Microlaryngeal Surgery (MLS, voice rest and speech therapy offer a cost effective, useful and safe

  3. Laparoscopic total pancreatectomy

    Science.gov (United States)

    Wang, Xin; Li, Yongbin; Cai, Yunqiang; Liu, Xubao; Peng, Bing

    2017-01-01

    Abstract Rationale: Laparoscopic total pancreatectomy is a complicated surgical procedure and rarely been reported. This study was conducted to investigate the safety and feasibility of laparoscopic total pancreatectomy. Patients and Methods: Three patients underwent laparoscopic total pancreatectomy between May 2014 and August 2015. We reviewed their general demographic data, perioperative details, and short-term outcomes. General morbidity was assessed using Clavien–Dindo classification and delayed gastric emptying (DGE) was evaluated by International Study Group of Pancreatic Surgery (ISGPS) definition. Diagnosis and Outcomes: The indications for laparoscopic total pancreatectomy were intraductal papillary mucinous neoplasm (IPMN) (n = 2) and pancreatic neuroendocrine tumor (PNET) (n = 1). All patients underwent laparoscopic pylorus and spleen-preserving total pancreatectomy, the mean operative time was 490 minutes (range 450–540 minutes), the mean estimated blood loss was 266 mL (range 100–400 minutes); 2 patients suffered from postoperative complication. All the patients recovered uneventfully with conservative treatment and discharged with a mean hospital stay 18 days (range 8–24 days). The short-term (from 108 to 600 days) follow up demonstrated 3 patients had normal and consistent glycated hemoglobin (HbA1c) level with acceptable quality of life. Lessons: Laparoscopic total pancreatectomy is feasible and safe in selected patients and pylorus and spleen preserving technique should be considered. Further prospective randomized studies are needed to obtain a comprehensive understanding the role of laparoscopic technique in total pancreatectomy. PMID:28099344

  4. Detection of rotator cuff lesions with indirect MR angiography

    International Nuclear Information System (INIS)

    Rudolph, J.; Lorenz, M.; Schroeder, R.; Felix, R.

    2000-01-01

    Purpose: To determine the value of indirect MR arthrography in lesions of the rotator cuff, prospectively versus arthroscopy. Methods: 63 patients with suspected shoulder pathology were examined: Oblique-coronary and axial T 1 w sequences, axial FLASH-2 D sequences, furthermore oblique-coronary T 2 - and PD-weighted sequences were taken. After intravenous administration of 0.1 mmol Gd-DTPA/kilogram body weight and active motion of the shoulder T 1 w sequences were repeated. Signal intensities (SI) inside the tendon were quantitatively measured by the ROI technique (region-of-interest) and the percentual contrast-enhancement CE was calculated. In 32 patients the results were confirmed by surgical follow-up. Results: The mean SI measured in the supraspinous tendon were higher in lesions (degeneration, impingement, partial and total rupture), before as well as after contrast medium, compared to intact findings (p [de

  5. A Cohort Study on Meniscal Lesions among Airport Baggage Handlers

    DEFF Research Database (Denmark)

    Mikkelsen, Sigurd; Brauer, Charlotte; Pedersen, Ellen Bøtker

    2016-01-01

    socioeconomic background and less knee-straining work. Baggage handlers lifted suitcases with an average weight of approximately 15 kg, in total approximately five tonnes during a 9-hour workday. The cohort was followed in the National Patient Register and Civil Registration System. The outcome was a first time......Meniscal lesions are common and may contribute to the development of knee arthrosis. A few case-control and cross-sectional studies have identified knee-straining work as risk factors for meniscal lesions, but exposure-response relations and the role of specific exposures are uncertain...... of unskilled men employed at Copenhagen Airport or in other companies in the metropolitan Copenhagen area from 1990 to 2012 (the Copenhagen Airport Cohort). The cohort at risk included 3,307 airport baggage handlers with heavy lifting and kneeling or squatting work tasks and 63,934 referents with a similar...

  6. Spinal accessory nerve schwannomas masquerading as a fourth ventricular lesion

    Directory of Open Access Journals (Sweden)

    Shyam Sundar Krishnan

    2015-01-01

    Full Text Available Schwannomas are benign lesions that arise from the nerve sheath of cranial nerves. The most common schwannomas arise from the 8 th cranial nerve (the vestibulo-cochlear nerve followed by trigeminal and facial nerves and then from glossopharyngeal, vagus, and spinal accessory nerves. Schwannomas involving the oculomotor, trochlear, abducens and hypoglossal nerves are very rare. We report a very unusual spinal accessory nerve schwannoma which occupied the fourth ventricle and extended inferiorly to the upper cervical canal. The radiological features have been detailed. The diagnostic dilemma was due to its midline posterior location mimicking a fourth ventricular lesion like medulloblastoma and ependymoma. Total excision is the ideal treatment for these tumors. A brief review of literature with tabulations of the variants has been listed.

  7. Estonian total ozone climatology

    Directory of Open Access Journals (Sweden)

    K. Eerme

    Full Text Available The climatological characteristics of total ozone over Estonia based on the Total Ozone Mapping Spectrometer (TOMS data are discussed. The mean annual cycle during 1979–2000 for the site at 58.3° N and 26.5° E is compiled. The available ground-level data interpolated before TOMS, have been used for trend detection. During the last two decades, the quasi-biennial oscillation (QBO corrected systematic decrease of total ozone from February–April was 3 ± 2.6% per decade. Before 1980, a spring decrease was not detectable. No decreasing trend was found in either the late autumn ozone minimum or in the summer total ozone. The QBO related signal in the spring total ozone has an amplitude of ± 20 DU and phase lag of 20 months. Between 1987–1992, the lagged covariance between the Singapore wind and the studied total ozone was weak. The spring (April–May and summer (June–August total ozone have the best correlation (coefficient 0.7 in the yearly cycle. The correlation between the May and August total ozone is higher than the one between the other summer months. Seasonal power spectra of the total ozone variance show preferred periods with an over 95% significance level. Since 1986, during the winter/spring, the contribution period of 32 days prevails instead of the earlier dominating 26 days. The spectral densities of the periods from 4 days to 2 weeks exhibit high interannual variability.

    Key words. Atmospheric composition and structure (middle atmosphere – composition and chemistry; volcanic effects – Meteorology and atmospheric dynamics (climatology

  8. Detection and Characterization of Focal Hepatic lesions using Magnetic resonance Imaging

    International Nuclear Information System (INIS)

    Pulgarin, Luis G; Delgado, Jorge Andres; Toro Nancy

    2008-01-01

    A retrospective one year study was performed from June 2006 to June 2007. A total of ten focal liver lesions in 60 patients were examined, describing their magnetic resonance (MR) characteristics, using T1, T2 and dynamic Gd-enhanced T1 weighted sequences with and without fat suppression. Lesions were classified into benign or malignant tumors and a diagnosis was proposed. Specific diagnoses such as simple cyst, abscess, hemangioma, focal nodular hyperplasia, hepatocellular carcinoma, and cholangiocarcinoma were reported.

  9. Frontal lobe syndrome from bilateral globus pallidus lesions a complication of Wernicke's encephalopathy

    OpenAIRE

    Arruda, Walter Oleschko

    1991-01-01

    A 38 year-old man developed the classical clinical picture of Wernicke's encephalopathy as a consequence of prolonged total parenteral nutrition. As a late complication he developed a frontal lobe syndrome. Bilateral globus pallidus lesions were observed in the CT-scan examination. Some aspects related to the cortical syndromes caused by subcortical lesions are discussed. Relata-se um caso de encefalopatia de Wernicke que ocorreu em paciente masculino de 38 anos, como complicação de alimen...

  10. Cortical chondroblastoma: report of a case and literature review of this lesion reported in unusual locations

    Energy Technology Data Exchange (ETDEWEB)

    Hameed, Meera R. [University of Medicine and Dentistry, New Jersey Medical School of Pathology, Newark, NJ (United States); New Jersey Medical School, Department of Pathology and Laboratory Medicine, Newark, NJ (United States); Blacksin, Marcia [University of Medicine and Dentistry, New Jersey Medical School of Radiology, Newark, NJ (United States); Das, Kasturi; Aisner, Seena [University of Medicine and Dentistry, New Jersey Medical School of Pathology, Newark, NJ (United States); Patterson, Francis; Benevenia, Joseph [University of Medicine and Dentistry, New Jersey Medical School of Orthopedic Surgery, Newark, NJ (United States)

    2006-05-15

    Chondroblastoma is a rare benign tumor occurring in adolescence and young adulthood, almost always involving the epiphysis of long bones. A 24-year-old man presented with a discrete soft-tissue lesion penetrating the cortex of the right distal femoral metadiaphyseal region. Biopsy revealed a chondroblastoma, and the patient subsequently underwent a total curettage of the lesion with cancellous bone graft from the iliac crest. (orig.)

  11. Total photon absorption

    International Nuclear Information System (INIS)

    Carlos, P.

    1985-06-01

    The present discussion is limited to a presentation of the most recent total photonuclear absorption experiments performed with real photons at intermediate energy, and more precisely in the region of nucleon resonances. The main sources of real photons are briefly reviewed and the experimental procedures used for total photonuclear absorption cross section measurements. The main results obtained below 140 MeV photon energy as well as above 2 GeV are recalled. The experimental study of total photonuclear absorption in the nuclear resonance region (140 MeV< E<2 GeV) is still at its beginning and some results are presented

  12. [Total artificial heart].

    Science.gov (United States)

    Antretter, H; Dumfarth, J; Höfer, D

    2015-09-01

    To date the CardioWest™ total artificial heart is the only clinically available implantable biventricular mechanical replacement for irreversible cardiac failure. This article presents the indications, contraindications, implantation procedere and postoperative treatment. In addition to a overview of the applications of the total artificial heart this article gives a brief presentation of the two patients treated in our department with the CardioWest™. The clinical course, postoperative rehabilitation, device-related complications and control mechanisms are presented. The total artificial heart is a reliable implant for treating critically ill patients with irreversible cardiogenic shock. A bridge to transplantation is feasible with excellent results.

  13. Radioguided occult lesion localization versus wire-guided localization for non-palpable breast lesions: randomized controlled trial

    International Nuclear Information System (INIS)

    Ocal, Koray; Dag, Ahmet; Turkmenoglu, Ozgur; Yucel, Erdem; Gunay, Emel Ceylan; Duce, Meltem Nass

    2011-01-01

    Aim: this prospective randomized clinical study was conducted to compare radioguided occult lesion localization (ROLL) with wire-guided localization to evaluate optimum localization techniques for non-palpable breast lesions. Methods: a total of 108 patients who were undergoing an excisional biopsy for non-palpable breast lesions requiring pathologic diagnosis were randomly assigned to the ROLL group (n 56) and wire-guided localization group (n 52). In the study, patients' characteristics, radiological abnormalities, radiological technique of localization, localization time, operation time, weight of the excised specimen, clearance margins, pathological diagnosis and perioperative complications were assessed. Results: there were no differences between the two groups in terms of age, radiological abnormalities and localization technique (p = non-significant for all). ROLL techniques resulted in 100% retrieval of the lesions; for the wire-guided localization technique, 98%. Both localization time and operation time were significantly reduced with the ROLL technique (p = significant for all). The weight of the specimen was significantly lower in the ROLL group than in the wire-guided localization group (p = significant). The overall complication rate and pathological diagnosis were similar for both groups (p = non-significant for all). Clear margins were achieved in 91% of ROLL patients and in 53% of wire-guided localization patients, and the difference was significant. Conclusions: the present study indicated that the ROLL technique is as effective as wire-guided localization for the excision of non-palpable breast lesions. In addition, ROLL improved the outcomes by reducing localization and operation time, preventing healthy tissue excision and achieving clearer margins. (author)

  14. Radioguided occult lesion localization versus wire-guided localization for non-palpable breast lesions: randomized controlled trial

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    Ocal, Koray; Dag, Ahmet; Turkmenoglu, Ozgur; Yucel, Erdem [Mersin University (Turkey). Medical Faculty. Dept. of General Surgery; Gunay, Emel Ceylan [Mersin University (Turkey). Medical Faculty. Dept. of Nuclear Medicine; Duce, Meltem Nass [Mersin University (Turkey). Medical Faculty. Dept. of Radiology

    2011-07-01

    Aim: this prospective randomized clinical study was conducted to compare radioguided occult lesion localization (ROLL) with wire-guided localization to evaluate optimum localization techniques for non-palpable breast lesions. Methods: a total of 108 patients who were undergoing an excisional biopsy for non-palpable breast lesions requiring pathologic diagnosis were randomly assigned to the ROLL group (n 56) and wire-guided localization group (n 52). In the study, patients' characteristics, radiological abnormalities, radiological technique of localization, localization time, operation time, weight of the excised specimen, clearance margins, pathological diagnosis and perioperative complications were assessed. Results: there were no differences between the two groups in terms of age, radiological abnormalities and localization technique (p = non-significant for all). ROLL techniques resulted in 100% retrieval of the lesions; for the wire-guided localization technique, 98%. Both localization time and operation time were significantly reduced with the ROLL technique (p = significant for all). The weight of the specimen was significantly lower in the ROLL group than in the wire-guided localization group (p = signific