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Sample records for chronic progressive radiation

  1. A case of chronic progressive radiation myelopathy treated with long-time corticosteroid administration

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Saeko; Soejima, Toshinori; Higashino, Takanori; Obayashi, Kayoko; Takada, Yoshiki [Hyogo Medical Center for Adults, Akashi (Japan); Hishikawa, Yoshio

    1998-05-01

    This is a report of one patient who developed chronic progressive radiation myelopathy at a gap of two portals 31 months after 40 Gy irradiation. He presented an unusual clinical course with over 5 years and 6 months administration of oral corticosteroid, very slow progression and long-lasting presentation of Gd-DTPA enhanced area in the suffered cord by MRI. It is suggested that corticosteroid administration from initial onset for a long period may change the natural course of radiation myelopathy, that is, may delay progress of it. (author)

  2. Case of chronic progressive radiation myelopathy with a CT myelogram simulating intramedullary tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kanemaru, Kazutomi; Kamo, Hisaki; Yamao, Satoshi; Akiguchi, Ichiro; Kameyama, Masakuni

    1985-05-01

    A 58-year-old man underwent a right middle lobectomy in June, 1975, for poorly differentiated adenocarcinoma of the lung. Postoperative irradiation was given to the hilus (6100 rads), and to the right supraclavicular area (6000 rads). In 1980, 60 months after completion of irradiation, the patient noticed weakness of his legs particularly on the left side. In 1982, he noticed the girdle sensation in the upper thoracic region, and paresthesia in the lateral side of the right thigh. In Dec 1983, micturition disturbance appeared, and gait disturbance progressed, he was admitted to the Kyoto University Hospital. Neurological examination revealed an incomplete left Brown-Sequard syndrome with diminution of pain and thermal sensation on the right lower limb, and weakness and spasticity particularly on the left lower limb. Conventional myelogram with CT myelogram showed spinal cord swelling from T-2 through T-5. No extramedullary lesion was found. Laminectomy was performed through T-1 to T-6. When the dura was opened, the cord was swollen and necrotic with a cyst formation. Microscopic examination of the thickened part of the cord showed necrosis and gliosis. The lesion was correspond to the cord segments exposed to the radiation, and a diagnosis of radiation myelopathy was made. Several cases of radiation myelopathy with definite swelling of the cord at myelography were reported, but myelography in these cases was performed at most within 11 months after the onset. In this case, myelography was performed three years after the onset, and revealed difinite swelling of the cord due to a cyst formation. (author).

  3. Chronic radiation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Akleyev, Alexander V. [Urals Research Centre for Radiation Medicine, Chelyabinsk (Russian Federation). Clinical Dept.

    2014-04-01

    Comprehensive analysis of chronic radiation syndrome, covering epidemiology, pathogenesis, pathoanatomy, diagnosis and treatment. Based on observations in a unique sample of exposed residents of the Techa riverside villages in the Urals. Casts new light on the condition. Of value for all practitioners and researchers with an interest in chronic radiation syndrome. This book covers all aspects of chronic radiation syndrome (CRS) based on observations in a unique sample of residents of the Techa riverside villages in the southern Urals who were exposed to radioactive contamination in the 1950s owing to releases of liquid radioactive wastes from Mayak Production Association, which produced plutonium for weapons. In total, 940 cases of CRS were diagnosed in this population and these patients were subjected to detailed analysis. The opening chapters address the definition and classification of CRS, epidemiology and pathogenesis, covering molecular and cellular mechanisms, radioadaptation, and the role of tissue reactions. The pathoanatomy of CRS during the development and recovery stages is discussed for all organ systems. Clinical manifestations of CRS at the different stages are then described in detail and the dynamics of hematopoietic changes are thoroughly examined. In the following chapters, principles of diagnosis (including assessment of the exposure doses to critical organs) and differential diagnosis from a wide range of other conditions are discussed and current and potential treatment options, described. The medical and social rehabilitation of persons with CRS is also covered. This book, which casts new light on the condition, will be of value for all practitioners and researchers with an interest in CRS.

  4. Chronic radiation myelitis.

    Science.gov (United States)

    Fitzgerald, R H; Marks, R D; Wallace, K M

    1982-08-01

    From March 1971 to September 1973, 200 patients with primary bronchogenic carcinoma received 4,000 rad (40 Gy) by means of split-course accelerated fractionation. Forty-five patients (22.5%) survived more than 11 months; and of these, 6 (13.3%) were found to have progressive myelitis. Recent reports indicate that rapid fractionation is preferred in some centers and may be undergoing a resurgence. The authors review their experience with this technique and the current understanding of the factors which affect the development of radiation myelitis.

  5. Acute radiation syndrome and chronic radiation syndrome.

    Science.gov (United States)

    Grammaticos, Philip; Giannoula, Evanthia; Fountos, George P

    2013-01-01

    Acute radiation syndrome (ARS) or sickness or poisoning or toxicity is induced after a whole body exposure of men to high doses of radiation between 1-12Gy. First symptoms are from the gastrointestinal system, which together with bone marrow are the most sensitive parts of our body. Chronic radiation syndrome (CRS) may be induced by smaller than 1Gy radiation doses or after a mild form of ARS. Prophylaxis and treatment suggestions are described. In cases of ARS, a large part of the exposed population after proper medical care may survive, while without medical care this part of the population will be lost. Prophylaxis may also save another part of the population.

  6. Chronic radiation enteritis and malnutrition.

    Science.gov (United States)

    Webb, Gwilym James; Brooke, Rachael; De Silva, Aminda Niroshan

    2013-07-01

    Radiation enteritis is defined as the loss of absorptive capacity of the intestine following irradiation, which is most commonly seen after radiotherapy for pelvic and abdominal malignancies. It is divided into acute and chronic forms and usually presents with diarrhea and malabsorption. Malnutrition is a common complication of chronic radiation enteritis (CRE). We reviewed the etiology, prevalence, symptoms, diagnosis and management of CRE and CRE with malnutrition in this article. Functional short bowel syndrome as a cause of malnutrition in CRE is also considered. The diagnostic work-up includes serum markers, endoscopy, cross-sectional imaging and the exclusion of alternative diagnoses such as recurrent malignancy. Management options of CRE include dietary manipulation, anti-motility agents, electrolyte correction, probiotics, parenteral nutrition, surgical resection and small bowel transplantation. Treatment may also be required for coexisting conditions including vitamin B12 deficiency, bile acid malabsorption and depression.

  7. Sleep disturbances in chronic progressive external ophthalmoplegia.

    NARCIS (Netherlands)

    Smits, B.W.; Westeneng, H.J.; Hal, M.A. van; Engelen, B.G.M. van; Overeem, S.

    2012-01-01

    BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. In addition to extraocular muscle weakness, various other organs can typically be affected, including laryngeal and limb muscles, cerebrum, cerebellum, and peripheral nerves. Given this mul

  8. Radiative Cooling: Principles, Progress, and Potentials.

    Science.gov (United States)

    Hossain, Md Muntasir; Gu, Min

    2016-07-01

    The recent progress on radiative cooling reveals its potential for applications in highly efficient passive cooling. This approach utilizes the maximized emission of infrared thermal radiation through the atmospheric window for releasing heat and minimized absorption of incoming atmospheric radiation. These simultaneous processes can lead to a device temperature substantially below the ambient temperature. Although the application of radiative cooling for nighttime cooling was demonstrated a few decades ago, significant cooling under direct sunlight has been achieved only recently, indicating its potential as a practical passive cooler during the day. In this article, the basic principles of radiative cooling and its performance characteristics for nonradiative contributions, solar radiation, and atmospheric conditions are discussed. The recent advancements over the traditional approaches and their material and structural characteristics are outlined. The key characteristics of the thermal radiators and solar reflectors of the current state-of-the-art radiative coolers are evaluated and their benchmarks are remarked for the peak cooling ability. The scopes for further improvements on radiative cooling efficiency for optimized device characteristics are also theoretically estimated.

  9. Recent progress in silica aerogel Cherenkov radiator

    CERN Document Server

    Tabata, Makoto; Kawai, Hideyuki; Kubo, Masato; Sato, Takeshi

    2012-01-01

    In this paper, we present recent progress in the development of hydrophobic silica aerogel as a Cherenkov radiator. In addition to the conventional method, the recently developed pin-drying method for producing high-refractive-index aerogels with high transparency was studied in detail. Optical qualities and large tile handling for crack-free aerogels were investigated. Sufficient photons were detected from high-performance aerogels in a beam test.

  10. Endoscopic management of chronic radiation proctitis.

    Science.gov (United States)

    Rustagi, Tarun; Mashimo, Hiroshi

    2011-11-01

    Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications. This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis.

  11. Endoscopic management of chronic radiation proctitis

    Institute of Scientific and Technical Information of China (English)

    Tarun Rustagi; Hiroshi Mashimo

    2011-01-01

    Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously, some lead to chronic symptoms including diarrhea, tenesmus, urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insufficient. There are very few controlled or prospective trials, and comparisons between therapies are limited because of different evaluation methods. Medical treatments, including formalin, topical sucralfate, 5-amino salicylic acid enemas, and short chain fatty acids have been used with limited success. Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe, neodymium:yttrium-aluminium-garnet laser, potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benefit, but with frequent complications. Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its efficacy and safety profile. Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application, with lower rate of complications.This review will focus on endoscopic ablation therapies, including such newer modalities, for chronic radiation proctitis.

  12. Chronic haemorrhagic radiation proctitis: A review

    Institute of Scientific and Technical Information of China (English)

    Vishnu Prasad Nelamangala Ramakrishnaiah; Srinivasan Krishnamachari

    2016-01-01

    Chronic haemorrhagic radiation proctitis(CHRP) is a difficult problem faced by the patients following radiation for pelvic malignancy. There is no standardtreatment for this condition, but many methods of treatment are available. The aim of this study was to review the literature to see whether there is an improvement in the available evidence in comparison with previously published systematic reviews in treating patients with CHRP. The Pub Med/Medline database and Google Scholar search was selectively searched. Studies, which treated patients with rectal bleeding due to chronic radiation proctitis or CHRP, were included. Seventy studies were finally selected out of which 14 were randomized controlled clinical trials. Though these studies could not be compared, it could be seen that there was an improvement in the methodology of the studies. There was an objective assessment of symptoms, signs and an objective assessment of outcomes. But, still, there were only a few studies that looked into the quality of life following treatment of CHRP. To increase recruitment to trials, a national registry of cases with established late radiation toxicity would facilitate the further improvement of such studies. Some of the conclusions that could be reached based on the available evidence are 4% formalin should be the first line treatment for patients with CHRP. Formalin and argon plasma coagulation(APC) are equally effective, but formalin is better for severe disease. Refractory patients, not responding to formalin or APC, need to be referred for hyperbaric oxygen therapy or surgery. Radio-frequency ablation is a promising modality that needs to be studied further in randomized trials.

  13. Novel biomarkers for progression of chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    LIU Bi-cheng; L(U) Lin-li

    2010-01-01

    @@ CHARACTERISTICS OF THE PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD) Although there are different initiators of CKD, it is generally recognized that the secondary pathological pathway is quite common to all CKD. CKD may inevitably progress to end stage renal disease (ESRD) due to a vicious cycle of nephron destruction by progressive glomerulosclerosis and tubulointerstitial fibrosis.

  14. Radiation transport: Progress report, July 1, 1987-September 30, 1987

    Energy Technology Data Exchange (ETDEWEB)

    O' Dell, R.D.; Nagy, A.

    1988-05-01

    Research and development progress in radiation transport for the Los Alamos National Laboratory's Group S-6 for the fourth quarter of FY 87 is reported. Included are unclassified tasks in the areas of Deterministic Radiation Transport, Monte Carlo Radiation Transport, and Cross Sections and Physics. 23 refs., 9 figs.

  15. Progress of radiation oncology: known and unknown

    Institute of Scientific and Technical Information of China (English)

    Liu Jing; Yu Jinming

    2014-01-01

    Objective To elaborate known and unknown aspects of radiation oncology.Data sources Data cited in this review were obtained mainly from PubMed and Medline in English from 1999 to 2013,with keywords "individualized medicine","personalized medicine","radiation dose","radiation target","molecular targeted therapy","molecular imaging" and "~nctional imaging".Study selection Articles regarding radiation target delineation,radiation doses,new technology and equipment,combination of radiotherapy and molecular targeted therapy as well as other aspects were identified,retrieved and reviewed.Results A larger radiation field and a higher radiation dose are not always better.New equipment and technology are also not always better than conventional equipment and technologies.Effectiveness of radiotherapy combined with molecular targeted therapy needs more data to verify.Conclusion Personalized radiotherapy is the direction for the future.

  16. Chronic radiation-induced dermatitis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Spałek M

    2016-12-01

    Full Text Available Mateusz Spałek Department of Radiotherapy I, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Abstract: Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF. RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and

  17. Enalapril dosage in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper;

    2005-01-01

    OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent ...

  18. Radiation transport. Progress report, April 1-December 31, 1983

    Energy Technology Data Exchange (ETDEWEB)

    O' Dell, R.D.

    1984-10-01

    Research and development progress in radiation transport by the Los Alamos National Laboratory's Group X-6 for the last nine months of CY 83 is reported. Included are unclassified tasks in the areas of Fission Reactor Neutronics, Deterministic Transport Methods, Monte Carlo Radiation Transport, and Cross Sections and Physics.

  19. PROGRESSION VARIANTS OF CHRONIC SYSTEMIC INFLAMMATION

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    E. Y. Gusev

    2009-01-01

    Full Text Available Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50; elderly persons 60 yrs old, as well as senior persons (n = 22; persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16; climacteric syndrome (n = 16; autoimmune thyroiditis (n = 29. The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI II-III stage (n=49; valvular cardiac disease (rheumatism, n = 15; psoriatic arthritis (n = 12; reactive arthritis (n = 17; antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5; systemic lupus erythematosus (n=49; decompensated atherosclerosis of femoral artery (n = 38; end-stage renal disease (n = 42. Plasma cytokines (TNFαα, IL-6, IL-8, IL-10, acute-phase C-reactive protein (CRP, cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR, and eosinophil cationic protein (ECP were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA. The integral indices of systemic inflammatory reaction (SIR have been calculated, i.e., a Reactivity Coefficient (RC and a Reactivity Level (RL. In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

  20. Formalin irrigation for hemorrhagic chronic radiation proctitis.

    Science.gov (United States)

    Ma, Teng-Hui; Yuan, Zi-Xu; Zhong, Qing-Hua; Wang, Huai-Ming; Qin, Qi-Yuan; Chen, Xiao-Xia; Wang, Jian-Ping; Wang, Lei

    2015-03-28

    To assess the efficacy and safety of a modified topical formalin irrigation method in refractory hemorrhagic chronic radiation proctitis (CRP). Patients with CRP who did not respond to previous medical treatments and presented with grade II-III rectal bleeding according to the Common Terminology Criteria for Adverse Events were enrolled. Patients with anorectal strictures, deep ulcerations, and fistulas were excluded. All patients underwent flexible endoscopic evaluation before treatment. Patient demographics and clinical data, including primary tumor, radiotherapy and previous treatment options, were collected. Patients received topical 4% formalin irrigation in a clasp-knife position under spinal epidural anesthesia in the operating room. Remission of rectal bleeding and related complications were recorded. Defecation, remission of bleeding, and other symptoms were investigated at follow-up. Endoscopic findings in patients with rectovaginal fistulas were analyzed. Twenty-four patients (19 female, 5 male) with a mean age of 61.5 ± 9.5 years were enrolled. The mean time from the end of radiotherapy to the onset of bleeding was 11.1 ± 9.0 mo (range: 2-24 mo). Six patients (25.0%) were blood transfusion dependent. The median preoperative Vienna Rectoscopy Score (VRS) was 3 points. Nineteen patients (79.2%) received only one course of topical formalin irrigation, and five (20.8%) required a second course. No side effects were observed. One month after treatment, bleeding cessation was complete in five patients and obvious in 14; the effectiveness rate was 79.1% (19/24). For long-term efficacy, 5/16, 1/9 and 0/6 patients complained of persistent bleeding at 1, 2 and 5 years after treatment, respectively. Three rectovaginal fistulas were found at 1 mo, 3 mo and 2 years after treatment. Univariate analysis showed associations of higher endoscopic VRS and ulceration score with risk of developing rectovaginal fistula. Modified formalin irrigation is an effective and safe

  1. Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kaspar-Josche Streitberger

    Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

  2. Acetaminophen, aspirin and progression of advanced chronic kidney disease

    NARCIS (Netherlands)

    Evans, Marie; Fored, Carl Michael; Bellocco, Rino; Fitzmaurice, Garrett; Fryzek, Jon P.; McLaughlin, Joseph K.; Nyren, Olof; Elinder, Carl-Gustaf

    2009-01-01

    Background. Although many studies have investigated the possible association between analgesic use (acetaminophen and aspirin) and the development of chronic kidney disease (CKD), the effect of analgesics on the progression of established CKD of any cause has not yet been investigated. Methods. In t

  3. Acetaminophen, aspirin and progression of advanced chronic kidney disease

    NARCIS (Netherlands)

    Evans, Marie; Fored, Carl Michael; Bellocco, Rino; Fitzmaurice, Garrett; Fryzek, Jon P.; McLaughlin, Joseph K.; Nyren, Olof; Elinder, Carl-Gustaf

    2009-01-01

    Background. Although many studies have investigated the possible association between analgesic use (acetaminophen and aspirin) and the development of chronic kidney disease (CKD), the effect of analgesics on the progression of established CKD of any cause has not yet been investigated. Methods. In t

  4. Progress in radiation immune thermionic integrated circuits

    Energy Technology Data Exchange (ETDEWEB)

    Lynn, D.K.; McCormick, J.B. (comps.)

    1985-08-01

    This report describes the results of a program directed at evaluating the thermionic integrated circuit (TIC) technology for applicability to military systems. Previous programs under the sponsorship of the Department of Energy, Office of Basic Energy Sciences, have developed an initial TIC technology base and demonstrated operation in high-temperature and high-radiation environments. The program described in this report has two parts: (1) a technical portion in which experiments and analyses were conducted to refine perceptions of near-term as well as ultimate performance levels of the TIC technology and (2) an applications portion in which the technical conclusions were to be evaluated against potential military applications. This report draws several conclusions that strongly suggest that (1) useful radiation-hard/high-temperature operable integrated circuits can be developed using the TIC technology; (2) because of their ability to survive and operate in hostile environments, a variety of potential military applications have been projected for this technology; and (3) based on the above two conclusions, an aggressive TIC development program should be initiated to provide the designers of future systems with integrated circuits and devices with the unique features of the TICs.

  5. Progress in radiation immune thermionic integrated circuits

    Energy Technology Data Exchange (ETDEWEB)

    Lynn, D.K.; McCormick, J.B. (comps.)

    1985-08-01

    This report describes the results of a program directed at evaluating the thermionic integrated circuit (TIC) technology for applicability to military systems. Previous programs under the sponsorship of the Department of Energy, Office of Basic Energy Sciences, have developed an initial TIC technology base and demonstrated operation in high-temperature and high-radiation environments. The program described in this report has two parts: (1) a technical portion in which experiments and analyses were conducted to refine perceptions of near-term as well as ultimate performance levels of the TIC technology and (2) an applications portion in which the technical conclusions were to be evaluated against potential military applications. This report draws several conclusions that strongly suggest that (1) useful radiation-hard/high-temperature operable integrated circuits can be developed using the TIC technology; (2) because of their ability to survive and operate in hostile environments, a variety of potential military applications have been projected for this technology; and (3) based on the above two conclusions, an aggressive TIC development program should be initiated to provide the designers of future systems with integrated circuits and devices with the unique features of the TICs.

  6. Central Blood Pressure and Chronic Kidney Disease Progression

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

  7. Chronic neuroendocrinological sequelae of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sklar, C.A. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Constine, L.S. [Univ. of Rochester Medical Center, Rochester, NY (United States)

    1995-03-30

    A variety of neuroendocrine disturbances are observed following treatment with external radiation therapy when the hypothalamic-pituitary axis (HPA) is included in the treatment field. Radiation-induced abnormalities are generally dose dependent and may develop many years after irradiation. Growth hormone deficiency and premature sexual development can occur following doses as low as 18 Gy fractionated radiation and are the most common neuroendocrine problems noted in children. Deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin are seen primarily in individuals treated with > 40 Gy HPA irradiation. Hyperprolactinemia can be seen following high-dose radiotherapy (>40 Gy), especially among young women. Most neuroendocrine disturbances that develop as a result of HPA irradiation are treatable; patients at risk require long-term endocrine follow-up. 23 refs., 6 figs., 2 tabs.

  8. Recent progress with the Transition Radiation Tracker

    CERN Document Server

    Froidevaux, D

    Start-up of end-cap assembly in Russia On July 2nd at PNPI (first photo) and on August 1st at JINR Dubna (second photo), the first straws were inserted into the first 4-plane end-cap wheels, each containing 3072 straws. The straws were glued, the radiator stacks were installed and the PNPI wheel was tested for gas leaks. An initial large leak rate was observed and fixed by increasing somewhat the amount of glue around each straw end-piece and improving the leak-tightness of the testing equipment itself. PNPI will assemble a total of 48 4-plane wheels of type A using two assembly lines. JINR Dubna will assemble a total of 32 4-plane wheels of type B using a single assembly line. The next steps are the gluing of the so-called active webs (printed circuit boards connecting high voltage and signal lines from straw/wire to HV supply and front-end boards), followed by wiring, and will take place in November. PNPI and JINR Dubna should start mass production in February-March next year. Barrel module produc...

  9. Prediction of fibrosis progression in chronic viral hepatitis

    Directory of Open Access Journals (Sweden)

    Grace Lai-Hung Wong

    2014-09-01

    Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

  10. Exercise training and the progression of chronic renal failure

    DEFF Research Database (Denmark)

    Eidemak, I; Haaber, A B; Feldt-Rasmussen, B

    1997-01-01

    The possible beneficial effect of regular exercise training on the progression of chronic renal failure was studied in a prospective randomized controlled study. Thirty patients with a median glomerular filtration rate (GFR) of 25 ml/(min.1.73 m2) (range 10-43) were randomized to physical training...... the rate of progression judged by the slope of GFR versus time plot was equal in the two groups. Hence, the beneficial effect of exercise training, earlier observed in rat studies, could not be reproduced in our patients. Physical exercise had no untoward effect on progression of renal disease....... (30 min of bicycling daily or an equal amount of other physical activities) or to maintenance of the usual lifestyle. The median maximal work capacity increased significantly in the exercise group and remained unchanged in the control group during a median observation time of 20 months whereas...

  11. Emerging risk factors and markers of chronic kidney disease progression.

    Science.gov (United States)

    Kronenberg, Florian

    2009-12-01

    Chronic kidney disease (CKD) is a common condition with an increasing prevalence. A number of comorbidities are associated with CKD and prognosis is poor, with many patients experiencing disease progression. Recognizing the factors associated with CKD progression enables high-risk patients to be identified and given more intensive treatment if necessary. The identification of new predictive markers might improve our understanding of the pathogenesis and progression of CKD. This Review discusses a number of emerging factors and markers for which epidemiological evidence from prospective studies indicates an association with progression of CKD. The following factors and markers are discussed: asymmetric dimethylarginine, factors involved in calcium-phosphate metabolism, adrenomedullin, A-type natriuretic peptide, N-terminal pro-brain natriuretic peptide, liver-type fatty acid binding protein, kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, apolipoprotein A-IV, adiponectin and some recently identified genetic polymorphisms. Additional epidemiological and experimental data are required before these markers can be broadly used for the prediction of CKD progression and before the risk factors can be considered as potential drug targets in clinical interventional trials.

  12. Progress Toward an Updated National Solar Radiation Data Base

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, S.; Anderberg, M.; George, R.; Marion, W.; Myers, D.; Renne, D.; Beckman, W.; DeGaetano, A.; Gueymard, C.; Perez, R.; Plantico, M.; Stackhouse, P.; Vignola, F.

    2005-01-01

    Progress is reported on an updated National Solar Radiation Database (NSRDB). Focus on this year's work was on preparing a test-year database for evaluating several solar radiation models that could be used to replace the METSTAT model used in the original 1961-1990 NSRDB. That model is no longer compatible with cloud observations reported by the National Weather Service. We have also included a satellite-based model that will increase the spatial resolution of solar radiation for GIS or mapping applications. Work also included development of improved estimates for aerosols, water vapor, and ozone. High-quality solar measurements were obtained for 33 sites near National Weather Service stations, and model runs were completed for test years 1999 and 2000.

  13. Effect of total lymphoid irradiation in chronic progressive multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cook, S.D.; Devereux, C.; Troiano, R.; Hafstein, M.P.; Zito, G.; Hernandez, E.; Lavenhar, M.; Vidaver, R.; Dowling, P.C.

    1986-06-21

    Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI has less functional decline than sham-irradiated MS patients (p<0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p<0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects.

  14. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

    To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

  15. Progress on an Updated National Solar Radiation Data Base: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, S.; Anderberg, M.; George, R.; Marion, W.; Myers, D.; Renne, D.; Beckman, W.; DeGaetano, A.; Gueymard, C.; Perez, R.; Plantico, M.; Stackhouse, P.; Vignola, F.

    2004-03-01

    In 1992, The National Renewable Energy Laboratory (NREL) released the 1961-1990 National Solar Radiation Data Base (NSRDB), a 30-year set of hourly solar radiation data. In April 2003, NREL convened a meeting of experts to investigate issues concerning a proposed update of the NSRDB. The panel determined that an important difficulty posed by the update was the shift from manual to automated cloud observations at National Weather Service stations in the United States. The solar model used in the original NSRDB relied heavily on the methodology and resolution of the manual cloud observations. The meeting participants recommended that NREL produce a plan for creating an update using currently available meteorological observations and satellite imagery. This paper describes current progress toward a plan for an updated NSRDB.

  16. Smart garments in chronic disease management: progress and challenges

    Science.gov (United States)

    Khosla, Ajit

    2012-10-01

    This paper presents the progress made developments in the area of Smart Garments for chronic disease management over last 10 years. A large number of health monitoring smart garments and wearable sensors have been manufactured to monitor patient's physiological parameters such as electrocardiogram, blood pressure, body temperature, heart rate, oxygen saturation, while patient is not in hospital. In last few years with the advancement in smartphones and cloud computing it is now possible to send the measure physiological data to any desired location. However there are many challenges in the development of smart garment systems. The two major challenges are development of new lightweight power sources and there is a need for global standardization and a road map for development of smart garments. In this paper we will discuss current state-of-theart smart garments and wearable sensor systems. Also discussed will be the new emerging trends in smart garment research and development.

  17. Radiological features of progressive tumoral calcinosis in chronic renal failure.

    LENUS (Irish Health Repository)

    Hodnett, P

    2012-02-03

    We present the case of a young adult patient with chronic renal failure who developed painful subcutaneous nodules after failed renal transplant and recommencing dialysis. These nodules were juxta-articular in location and initially located over both shoulders. Radiological evaluation suggested tumoral calcinosis. The patient was placed on a strict dialysis and dietary regimen but was suboptimally compliant with same. The patient developed progressive disease with an increase in size and number of juxta-articular calcified soft-tissue masses. However, 6 months following a second renal transplant clinical and radiological follow up demonstrated marked resolution both in symptomatology and radiographic findings. We present the plain radiographic, CT and MRI findings which demonstrate the typical radiological features of tumoral calcinosis. We correlate these findings with clinical course and histological findings following surgical excision of one of these masses.

  18. Acidosis: progression of chronic kidney disease and quality of life.

    Science.gov (United States)

    de-Brito Ashurst, Ione; O'Lone, Emma; Kaushik, Tarun; McCafferty, Kieran; Yaqoob, Muhammad M

    2015-06-01

    Metabolic acidosis (MA) is relatively common in patients with chronic kidney disease (CKD) particularly in stages 4 and 5. It is assumed to play a contributory role in the development of several complications including bone disease, skeletal muscle wasting, altered protein synthesis, and degradation. Recent evidence also suggests that even mild acidosis might play a role in progressive glomerular filtration rate loss. Experimental and clinical studies suggest that correction of acidosis by alkali therapy attenuates these complications and improves quality of life. Despite several recent small and single-center studies supporting this notion, more robust evidence is required with regard to the long-term benefits of alkali therapy, type of alkali supplements, and the optimal level of serum bicarbonate.

  19. Applications of acoustic radiation force impulse quantification in chronic kidney disease: A review

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Liang [Dept. of Ultrasound, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing (China)

    2016-08-15

    Acoustic radiation force impulse (ARFI) imaging is an emerging technique with great promise in the field of elastography. Previous studies have validated ARFI quantification as a method of estimating fibrosis in chronic liver disease. Similarly, fibrosis is the principal process underlying the progression of chronic kidney disease, which is the major cause of renal failure. However, the quantification of tissue stiffness using ARFI imaging is more complex in the kidney than in the liver. Moreover, not all previous studies are comparable because they employed different procedures. Therefore, subsequent studies are warranted, both in animal models and in clinical patients, in order to better understand the histopathological mechanisms associated with renal elasticity and to further improve this imaging method by developing a standardized guidelines for its implementation.

  20. Progression from acute to chronic pancreatitis: prognostic factors, mortality, and natural course

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Becker, Ulrik; Matzen, Peter

    2011-01-01

    Knowledge of the natural course of acute pancreatitis (AP) and risk of progression to chronic pancreatitis (CP) is limited. The aims were to describe: (1) the incidence of progression from AP to CP, (2) prognostic factors for progression, and (3) the natural course and mortality of progressive AP....

  1. Neuropsychological Findings in Relapsing-Remitting and Chronic-Progressive Multiple Sclerosis.

    Science.gov (United States)

    Heaton, Robert K.; And Others

    1985-01-01

    Assessed neuropsychological functioning in 100 patients who had relapsing-remitting or chronic-progressive courses of multiple sclerosis (MS). Both MS subgroups showed significant neuropsychological impairment, relative to a normal comparison group (N=100), but chronic-progressive MS was associated with greater impairment in each major ability…

  2. Progress in radiation vulcanization of natural rubber latex

    Energy Technology Data Exchange (ETDEWEB)

    Makuuchi, Keizo [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2000-03-01

    Vulcanization dose defined as the radiation dose at which cross-linked natural rubber in latex has the maximum tensile strength can be reduced by adding carbon tetrachloride as a reaction accelerator. The radiation vulcanization of natural rubber latex was selected as one of regional projects of IAEA in 1989 and a pilot plant was built in Jakarta. The products from it were evaluated during 1983-1985, followed by IAEA decision to support the continued R and D study at Takasaki, JAERI. Various factors to improve the properties of the products have been studied. Several advantages of the process over conventional method, such as absence of N-nitrosoamines, low cytotoxicity, decomposability in the environment, transparency and softness, were confirmed. The technology has been transferred toward commercial application in Thailand, and pilot plants being set up in Indonesia, India, Malaysia and Thailand. Moreover, the process was found to be effective in reducing protein remaining in natural rubber latex products and the initial investment and irradiation cost was found to be greatly reduced by employing low energy electron accelerator. This paper reviews such progress. (S. Ohno)

  3. Progress in radiation vulcanization of natural rubber latex

    Energy Technology Data Exchange (ETDEWEB)

    Makuuchi, Keizo [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2000-03-01

    Vulcanization dose defined as the radiation dose at which cross-linked natural rubber in latex has the maximum tensile strength can be reduced by adding carbon tetrachloride as a reaction accelerator. The radiation vulcanization of natural rubber latex was selected as one of regional projects of IAEA in 1989 and a pilot plant was built in Jakarta. The products from it were evaluated during 1983-1985, followed by IAEA decision to support the continued R and D study at Takasaki, JAERI. Various factors to improve the properties of the products have been studied. Several advantages of the process over conventional method, such as absence of N-nitrosoamines, low cytotoxicity, decomposability in the environment, transparency and softness, were confirmed. The technology has been transferred toward commercial application in Thailand, and pilot plants being set up in Indonesia, India, Malaysia and Thailand. Moreover, the process was found to be effective in reducing protein remaining in natural rubber latex products and the initial investment and irradiation cost was found to be greatly reduced by employing low energy electron accelerator. This paper reviews such progress. (S. Ohno)

  4. DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease

    OpenAIRE

    Zeybel, Müjdat; Karahüseyinoğlu, Serçin; Vatansever, Sezgin; Hardy, Timothy; Sarı, Aysegül Akder; Çakalağaoğlu, Fulya; Avcı, Arzu; Zeybel, Gemma Louise; Bashton, Matthew; Mathers, John C.; Ünsal, Belkis; Mann, Jelena

    2016-01-01

    Background: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. Results: To identify epigenetic marks associated with inflammatory and fibrotic processes of t...

  5. [Case of chronic progressive encephalo-myelo-radiculo-neuropathy].

    Science.gov (United States)

    Kutoku, Yumiko; Inoue, Ken; Murakami, Tatsufumi; Sunada, Yoshihide

    2010-05-01

    A 65-year-old man developed urinary impairment and gait disturbance over a period of four months. On admission, neurological examinations revealed paraplegia, decreased deep tendon reflexes in the extremities, bilateral positive Babinski and Chaddock signs, superficial and deep sensory disturbances and neurogenic bladder. Cerebrospinal fluid examination disclosed a total cell count of 70/mm3, and protein of 76 mg/dl. Nerve conduction studies and somatosensory evoked potential suggested demyelinating neuropathy and myelopathy. Brain MRI revealed irregular-shaped white matter lesions distributed over the bilateral cerebral hemispheres and the brain stem. In addition spinal MRI disclosed long spinal cord lesions disseminated from the higher cervical to the lower thoracic spine. A 1 microm-thick epon-embedded section and teased fiber preparations of a biopsied sural nerve showed segmental demyelination and remyelination. Treatments using intravenous methylprednisolone and IVIg were both effective. The positive responses to immunological treatment, along with the findings, strongly suggested that the demyelinating lesions occurred in both the central and peripheral nervous systems. We regarded this case as one of chronic progression of Encephalo-myelo-radiculo-neuropathy.

  6. Tubular atrophy in the pathogenesis of chronic kidney disease progression.

    Science.gov (United States)

    Schelling, Jeffrey R

    2016-05-01

    The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.

  7. Chronic radiation proctopathy:A practical review of endoscopic treatment

    Institute of Scientific and Technical Information of China (English)

    Luciano Lenz; Rachel Rohr; Frank Nakao; Ermelindo Libera; Angelo Ferrari

    2016-01-01

    Chronic radiation proctopathy(CRP) is a troublesome complication of pelvic radiotherapy. The most common presentation is rectal bleeding. CRP symptoms interfere with daily activities and decrease quality of life. Rectal bleeding management in patients with CRP represents a conundrum for practitioners. Medical therapy is ineffective in general and surgical approach has a high morbidmortality. Endoscopy has a role in the diagnosis,staging and treatment of this disease. Currently available endoscopic modalities are formalin,potassium titanyl phosphate laser,neodymium:yttrium-aluminum-garnet laser,argon laser,bipolar electrocoagulation(BiCAP),heater probe,band ligation,cryotherapy,radiofrequency ablation and argon plasma coagulation(APC). Among these options,APC is the most promising.

  8. Effects in Plant Populations Resulting from Chronic Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, Stanislav A.; Volkova, Polina Yu.; Vasiliyev, Denis V.; Dikareva, Nina S.; Oudalova, Alla A. [Russian Institute of Agricultural Radiology and Agroecology, 249032, Obninsk (Russian Federation)

    2014-07-01

    environment activates genetic mechanisms, changing a population's resistance to exposure. However, there are ecological situations in which enhanced resistance has not evolved or has not persisted. Consequently, there are good theoretical and practical reasons for more attention being paid to the mechanisms by which populations becomes more radioresistant and to those situations where radio-adaptation appears not to be taking place. Since radio-adaptation plays an important role in response of populations on radiation exposure, this process needs to be incorporated into management programmes. To this very day, the effects of chronic exposure on living organisms and populations remain poorly explored, and represent a much needed field of research. In spite of the long history of the research, we are still far from complete understanding underlying processes in exposed populations. Neglecting field-collected data in favour of simplified short-term experiments that tend to overestimate adverse effects will obviously have detrimental effect for understanding, predicting, and mitigating consequences of the radiation impact on the environment. Much more is to be elucidated in our understanding before we will be able to give an objective and comprehensive assessment of the biological consequences of chronic, low-level radiation exposures to natural plant and animal populations. (authors)

  9. Progression From Acute to Chronic Pancreatitis Prognostic Factors, Mortality, and Natural Course

    DEFF Research Database (Denmark)

    Nojgaard, C.; Becker, U.; Matzen, Peter

    2011-01-01

    Objectives: Knowledge of the natural course of acute pancreatitis (AP) and risk of progression to chronic pancreatitis (CP) is limited. The aims were to describe: (1) the incidence of progression from AP to CP, (2) prognostic factors for progression, and (3) the natural course and mortality...

  10. Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study.

    Science.gov (United States)

    Klistorner, Alexander; Wang, Chenyu; Yiannikas, Con; Graham, Stuart L; Parratt, John; Barnett, Michael H

    2016-01-01

    To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS) as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months. The optic radiation (OR) was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co-registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD) and radial diffusivity (RD) within OR lesions and non-lesional normal appearing white matter (NAWM) was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions). Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001) increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively). In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes. The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

  11. Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study.

    Directory of Open Access Journals (Sweden)

    Alexander Klistorner

    Full Text Available To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months.The optic radiation (OR was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co-registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD and radial diffusivity (RD within OR lesions and non-lesional normal appearing white matter (NAWM was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions.Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001 increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9% and RD (M-4.6%, F-0.7% was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively. In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes.The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

  12. Late health effects of chronic radiation exposure of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

    2014-07-01

    infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  13. EFFECT OF LOSARTAN ON SLOWING PROGRESSION OF CHRONIC ALLOGRAFT NEPHROPATHY

    Institute of Scientific and Technical Information of China (English)

    Ping-xian Wang; Ming-qi Fan; Chi-bing Huang; Jia-yu Feng; Ya Xiao; Zhen-qiang Fang; Yin-pu Zhang

    2005-01-01

    Objective To investigate the effects of losartan, a specific angiotensin Ⅱ receptor blocker, on slowing progression of renal insufficiency in patients with biopsy-proven chronic allograft nephropathy (CAN) and the molecular mechanism of the therapy.Methods Twenty-two renal transplant recipients with biopsy-proven CAN (group A) were treated with losartan within two months after renal dysfunction for at least one year. Losartan was administered at a dose of 50 mg/d. Twenty-four recipients in the same fashion (group B) who never received angiotensin Ⅱ receptor antagonist were studied as control. The investigation time for each patient lasted one year. Renal functions and concentrations of plasma and urine transforming growth factor-beta1 (TGF-beta1) were compared between the two groups at the initiation and end of the study. In group A, expressions of TGF-beta1 mRNA and immunofluorescence intensity of TGF-beta1 protein and pathological alterations in renal biopsy specimens were compared between before losartan therapy and after one year of the therapy.Results At the initiation of the investigation, no significant differences were found between group A and group B in clinical data such as donor age, cold-ischemia time, HLA mismatch, levels of creatinine clearance (Ccr), plasma and urineTGF-beta1 concentrations. One year later, 14 of 22 (63.6%) patients showed stable or improved graft functions in group A,and 4 of 24 (16.7%) in group B. The difference was significant (P<0.05). At the end of the study, urine TGF-beta1 loss of Ccr was 6.6±5.4 mL/min in group A and 16.2±9.1 mL/min in group B. Both of the differences were significant between the two groups (P<0.01). No significant differences were found in plasma TGF-beta1 concentrations between the four values determined at the initiation and end of the study in the two groups (F = 2.56, P > 0.05). After one year losartan therapy, group A showed a significant decrease in expressions of TGF-beta1 mRNA and TGF

  14. Nature and frequency of respiratory involvement in chronic progressive external ophthalmoplegia

    NARCIS (Netherlands)

    Smits, B.W.; Heijdra, Y.F.; Cuppen, F.; Engelen, B.G. van

    2011-01-01

    Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. Weakness of the extra-ocular, limb girdle and laryngeal muscles are established clinical features. Respiratory muscle involvement however has never been studied systematically, even though respiratory

  15. Analysis of reproductive function in persons exposed to chronic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kossenko, M.M.; Ostroumova, E.V.; Vyushkova, O.V. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2000-05-01

    The purpose of the study was to analyze the reproductive function in individuals exposed to radiation in the riverside villages on the Techa in the Southern Urals. The exposure of the population, numbering 28000, occurred in 1950-1956 as a result of discharges into the river of radioactive wastes from the Mayak facility for processing weapon plutonium. The residents were exposed to chronic radiation, both external and internal. The range of exposure doses to gonads was sufficiently wide: 20-1270 mSv. However, the distribution of doses among the exposed individuals was ununiform, and the proportion of people whose dose was below 120 mGy accounted for 74%. The following characteristics of exposed women were analyzed: menstrual function, outcomes of pregnancy, birth rates, health status for newborns. The analysis of the menstrual function in exposed women showed that in persons exposed in childhood, menarche was registered at the age of 14.3 years, on the average (based on literature sources, menarche is attained at the age of 13 for unexposed population). The mean age at menopause was 47.9 years for exposed women (the respective mean value for Russia is 50.8 years). Pregnancy outcomes were analyzed in 9000 exposed women. The rate of medical and criminal abortions was estimated as 79 per 100 labors. The rate of spontaneous abortions for exposed women was slightly higher, 3.11%, than for controls, 2.30%; these difference, however, were statistically insignificant. The total loss of fetus or neonate (unfavorable outcomes of pregnancy: spontaneous abortions, stillbirths, early neonatal death) was estimated to be 4.58% at zero dose. Exposure to gonads at the dose 1 Sv, estimated using the above-indicated method, yielded 3% of additional unfavorable outcomes of pregnancy. It was shown, based on the analysis of birth rates for the Techa Cohort that they had not undergone any essential changes over the first 25 years of exposure compared to the respective coefficients for

  16. Dietary Energy Density, Renal Function, and Progression of Chronic Kidney Disease

    OpenAIRE

    2016-01-01

    Background. There is evidence of the association between dietary energy density and chronic diseases. However, no report exists regarding the relation between DED and chronic kidney disease (CKD). Objective. To examine the association between dietary energy density (DED), renal function, and progression of chronic kidney disease (CKD). Design. Cross-sectional. Setting. Three nephrology clinics. Subjects. Two hundred twenty-one subjects with diagnosed CKD. Main Outcome Measure. Dietary intake ...

  17. Risk factors of progression of chronic kidney disease patients under conservative treatment

    Directory of Open Access Journals (Sweden)

    Tarek A. Ghonemy

    2015-10-01

    Conclusions: The most important risk factors for rapid progression are presence of diabetes, severity of proteinuria and low serum bicarbonate level in advanced stages of chronic kidney disease. Early recognition of these risk factors and their correction may retard the progression of CKD, which will delay the need for renal replacement therapy. In addition, ACEI or ARBs intake are almost renoprotective and may delay the rapid progression of chronic kidney disease especially in proteinuric patients. [Int J Res Med Sci 2015; 3(10.000: 2734-2739

  18. Progress in the Development of Plasma Panel Radiation Detectors

    CERN Document Server

    Ball, Robert; Benhammou, Yan; Moshe, Meny Ben; Chapman, J Wehrley; Dai, Tiesheng; Etzion, Erez; Friedman, Peter S; Levin, Daniel S; Silver, Yiftah; Sherman, Guy; Varner, Robert L; Weaverdyck, Curtis; White, Steve; Yu, J; Zhou, Bing

    2011-01-01

    Plasma Display Panels (PDP), the underlying engine of panel plasma television displays, are being investigated for their utility as radiation detectors called Plasma Panel Sensors (PPS). The PPS a novel variant of a micropattern radiation detector, is intended to be a fast, high resolution detector comprised of an array of plasma discharge cells operating in a hermetically sealed gas mixture. We report on the PPS development effort, including recent laboratory measurements.

  19. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation. PMID:26795421

  20. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  1. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-22

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  2. Radiation effects in nuclear waste materials. 1998 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.J.; Corrales, L.R. [Pacific Northwest National Lab., Richland, WA (US); Birtcher, R.C. [Argonne National Lab., IL (US); Nastasi, M. [Los Alamos National Lab., NM (US)

    1998-06-01

    'The objective of this multidisciplinary, multi-institutional research effort is to develop a fundamental understanding of radiation effects in glasses and ceramics at the atomic, microscopic, and macroscopic levels. The goal is to provide the underpinning science and models necessary to assess the performance of glasses and ceramics designed for the immobilization and disposal of high-level tank waste, plutonium residues, excess weapons plutonium, and other highly radioactive waste streams. A variety of experimental and computer simulation methods are employed in this effort. In general, research on glasses focuses on the electronic excitations due to ionizing radiation emitted from beta decay, since this is currently thought to be the principal mechanism for deleterious radiation effects in nuclear waste glasses. Research on ceramics focuses on defects and structural changes induced by the elastic interactions between alpha-decay particles and the atoms in the structure. Radiation effects can lead to changes in physical and chemical properties that may significantly impact long-term performance of nuclear waste materials. The current lack of fundamental understanding of radiation effects in nuclear waste materials makes it impossible to extrapolate the limited existing data bases to larger doses, lower dose rates, different temperature regimes, and different glass compositions or ceramic structures. This report summarizes work after almost 2 years of a 3-year project. Work to date has resulted in 9 publications. Highlights of the research over the past year are presented.'

  3. Progress report on the neutral beam radiation hardening study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.D.; Condit, R.H.; Hoenig, C.L.; Wilcox, T.P.; Erickson, J.

    1978-10-01

    A neutral beam injector as presently conceived directly views the plasma it is sustaining. In turn the injector is exposed to the primary fusion neutrons plus secondary neutrons and gammas streaming back up the neutral beam duct. The intent of this work is to examine representative beam lines to see how performance and lifetimes could be affected by this radiation environment and to determine how unacceptable effects could be alleviated. Potential radiation induced problems addressed in this report have been limited to: (1) overheating of cryopanels and insulators, (2) gamma flux induced electrical conductivity increase of insulators, and (3) neutron and gamma fluence induced damage to insulator materials.

  4. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril....... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  5. [Fear of progression in patients with cancer, diabetes mellitus and chronic arthritis].

    Science.gov (United States)

    Dankert, A; Duran, G; Engst-Hastreiter, U; Keller, M; Waadt, S; Henrich, G; Herschbach, P

    2003-06-01

    Fear of an increasing disease progression (fear of progression) is among the main psychological stresses in patients with cancer, diabetes mellitus (type 1 and type 2) and chronic arthritis. The questions the study seeks to answer are: (1) Which are the main fears of these patients?, (2) How and in which circumstances in life do they occur?, (3) Which are the triggers of the fear? To answer these questions, a sample of 65 patients were researched through interviews. The results indicate that the predominant fears of cancer patients are the fear of dying and the unpredictability of the progression of the disease. Patients with chronic arthritis most frequently fear being physically dependent on someone else. The most common anxiety of diabetes patients are long-term complications. For all three groups of patients job-related fears cause a high amount of distress. These results contribute to the development of a standardised fear of progression questionnaire.

  6. Neglected tropical diseases: progress towards addressing the chronic pandemic.

    Science.gov (United States)

    Molyneux, David H; Savioli, Lorenzo; Engels, Dirk

    2017-01-21

    The concept of neglected tropical diseases (NTDs) emerged more than a decade ago and has been recognised as a valid way to categorise diseases that affect the poorest individuals. Substantial progress in control and elimination has been achieved and policy momentum has been generated through continued bilateral, philanthropic, and non-governmental development organisation (NGDO) support, and donations of drugs from pharmaceutical companies. WHO has defined a Roadmap to reach 2020 targets, which was endorsed by member states in a World Health Assembly Resolution in 2013. NTDs have been included within the Sustainable Development Goal targets and are a crucial component of universal health coverage, conceptualised as "leaving no one behind". WHO reported that more than 1 billion people in 88 countries have benefited from preventive chemotherapy in 2014. The research agenda has defined the need for affordable products (diagnostics, drugs and insecticides). However challenges such as insecurity and weak health systems continue to prevail in the poorest countries, inhibiting progress in scaling up and also in achieving Roadmap goals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Injury of the blood-testies barrier after low-dose-rate chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Young Hoon; Bae Min Ji; Lee, Chang Geun; Yang, Kwang Mo; Jur, Kyu; Kim, Jong Sun [Dongnam Institute of Radiological and Medical Science, Busan (Korea, Republic of)

    2014-04-15

    The systemic effect of radiation increases in proportionally with the dose and dose rate. Little is known concerning the relationships between harmful effects and accumulated dose, which is derived from continuous low-dose rate radiation exposure. Recent our studies show that low-dose-rate chronic radiation exposure (3.49 mGy/h) causes adverse effects in the testis at a dose of 2 Gy (6 mGy/h). However, the mechanism of the low-dose-rate 2 Gy irradiation induced testicular injury remains unclear. The present results indicate that low-dose rate chronic radiation might affect the BTB permeability, possibly by decreasing levels of ZO-1, Occludin-1, and NPC-2. Furthermore, our results suggest that there is a risk of male infertility through BTB impairment even with low-dose-rate radiation if exposure is continuous.

  8. Current progress in the treatment of chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Alexandra Alexopoulou; George V Papatheodoridis

    2012-01-01

    Over the last decade,the standard of care for the treatment of chronic hepatitis C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin (RBV)which results in sustained virological response (SVR)rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1.Currently,there are rapid and continuous developments of numerous new agents against hepatitis C virus (HCV),which are the focus of this review.Boceprevir and telaprevir,two first-generation NS3/4A HCV protease inhibitors,have been recently licensed in several countries around the world to be used in combination with PEGIFN and RBV for the treatment of genotype 1 patients.Boceprevir or telaprevir based triple regimens,compared with the PEG-IFN/RBV combination,improve the SVR rates by 25%-31% in treatment-naive genotype 1 patients,by 40%-64% in prior relapsers,by 33%-45% in prior partial responders and by 24%-28% in prior null responders.At the same time,the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-naive patients.There are,however,several challenges with the use of the new triple combinations in genotype 1 patients,such as the need for immediate results of HCV RNA testing using sensitive quantitative assays,new and more frequent adverse events (anemia and dysgeusia for boceprevir; pruritus,rash and anemia for telaprevir),new drug interactions and increasing difficulties in compliance.Moreover,the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients,such as null responders with cirrhosis,while there is no benefit for patients who cannot tolerate PEGIFN/RBV or who are infected with non-1 HCV genotype.Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results.Preliminary data

  9. Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

    Science.gov (United States)

    Chang, Jia-Feng; Yeh, Jih-Chen; Chiu, Ya-Lin; Liou, Jian-Chiun; Hsiung, Jing-Ru; Tung, Tao-Hsin

    2017-01-01

    No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Novel trophic niches drive variable progress towards ecological speciation within an adaptive radiation of pupfishes.

    Science.gov (United States)

    Martin, Christopher H; Feinstein, Laura C

    2014-04-01

    Adaptive radiation is recognized by a rapid burst of phenotypic, ecological and species diversification. However, it is unknown whether different species within an adaptive radiation evolve reproductive isolation at different rates. We compared patterns of genetic differentiation between nascent species within an adaptive radiation of Cyprinodon pupfishes using genotyping by sequencing. Similar to classic adaptive radiations, this clade exhibits rapid morphological diversification rates and two species are novel trophic specialists, a scale-eater and hard-shelled prey specialist (durophage), yet the radiation is adaptive landscapes underlying these two niche environments drive variable progress towards speciation within the same habitat. Our previous measurements of fitness surfaces in these lakes support this conclusion: the scale-eating fitness peak may be more distant than the durophage peak on the complex adaptive landscape driving adaptive radiation. © 2014 John Wiley & Sons Ltd.

  11. Prion protein polymorphisms affect chronic wasting disease progression.

    Directory of Open Access Journals (Sweden)

    Chad J Johnson

    Full Text Available Analysis of the PRNP gene in cervids naturally infected with chronic wasting disease (CWD suggested that PRNP polymorphisms affect the susceptibility of deer to infection. To test this effect, we orally inoculated 12 white-tailed deer with CWD agent. Three different PRNP alleles, wild-type (wt; glutamine at amino acid 95 and glycine at 96, Q95H (glutamine to histidine at amino acid position 95 and G96S (glycine to serine at position 96 were represented in the study cohort with 5 wt/wt, 3 wt/G96S, and 1 each wt/Q95H and Q95H/G96S. Two animals were lost to follow-up due to intercurrent disease. The inoculum was prepared from Wisconsin hunter-harvested homozygous wt/wt animals. All infected deer presented with clinical signs of CWD; the orally infected wt/wt had an average survival period of 693 days post inoculation (dpi and G96S/wt deer had an average survival period of 956 dpi. The Q95H/wt and Q95H/G96S deer succumbed to CWD at 1,508 and 1,596 dpi respectively. These data show that polymorphisms in the PRNP gene affect CWD incubation period. Deer heterozygous for the PRNP alleles had extended incubation periods with the Q95H allele having the greatest effect.

  12. Prion protein polymorphisms affect chronic wasting disease progression.

    Science.gov (United States)

    Johnson, Chad J; Herbst, Allen; Duque-Velasquez, Camilo; Vanderloo, Joshua P; Bochsler, Phil; Chappell, Rick; McKenzie, Debbie

    2011-01-01

    Analysis of the PRNP gene in cervids naturally infected with chronic wasting disease (CWD) suggested that PRNP polymorphisms affect the susceptibility of deer to infection. To test this effect, we orally inoculated 12 white-tailed deer with CWD agent. Three different PRNP alleles, wild-type (wt; glutamine at amino acid 95 and glycine at 96), Q95H (glutamine to histidine at amino acid position 95) and G96S (glycine to serine at position 96) were represented in the study cohort with 5 wt/wt, 3 wt/G96S, and 1 each wt/Q95H and Q95H/G96S. Two animals were lost to follow-up due to intercurrent disease. The inoculum was prepared from Wisconsin hunter-harvested homozygous wt/wt animals. All infected deer presented with clinical signs of CWD; the orally infected wt/wt had an average survival period of 693 days post inoculation (dpi) and G96S/wt deer had an average survival period of 956 dpi. The Q95H/wt and Q95H/G96S deer succumbed to CWD at 1,508 and 1,596 dpi respectively. These data show that polymorphisms in the PRNP gene affect CWD incubation period. Deer heterozygous for the PRNP alleles had extended incubation periods with the Q95H allele having the greatest effect.

  13. Molecular events basic to cellular radiation response. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Kolodny, G.M.

    1976-01-01

    Studies on regulation of gene expression included research projects on turnover of ribosomal RNA, ribonuclease-resistant oligonucleotides, and reutilization of oligonucleotides. Studies on radiation effects on RNA included research projects on radioinduced strand breaks in RNA and radioinduced alterations in RNA nucleotides. Effects of vasopression on radiosensitivity were studied. Studies on amino acid-nucleic acid interactions included research projects on synthesis and spectroscopic analysis of nucleotide-amino acid covalently bonded model compound and intermolecular interactions between tryptophan and dinucleoside phosphates. (HLW)

  14. Structured approach to design of diagnostic test evaluation studies for chronic progressive infections in animals

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew

    2011-01-01

    Diagnostic test evaluations (DTEs) for chronic infections are challenging because a protracted incubation period has to be considered in the design of the DTE, and the adverse effects of infection may be widespread and progressive over an animal's entire life. Frequently, the specific purpose of ...

  15. Urine liver fatty acid binding protein and chronic kidney disease progression

    DEFF Research Database (Denmark)

    Khatir, Dinah S; Bendtsen, Mette D; Birn, Henrik

    2017-01-01

    , regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, (51)Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L...

  16. Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

    Science.gov (United States)

    Mackenzie, Catherine; Green, Jan

    2009-01-01

    Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

  17. Familial progressive neuronal disease and chronic idiopathic intestinal pseudo-obstruction.

    Science.gov (United States)

    Steiner, I; Steinberg, A; Argov, Z; Faber, J; Fich, A; Gilai, A

    1987-06-01

    Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterized by recurrent episodes of bowel obstruction without mechanical cause. In five members of two Jewish-Iranian families, CIIP was associated with progressive neuronal disease, starting before age 30, with ophthalmoplegia, sensorimotor peripheral neuropathy, and hearing loss. There was no evidence of CNS involvement. The pattern suggested autosomal recessive inheritance.

  18. Morphological and Biochemical Evaluation of Progression of Chronic Hepatitis Associated with C Virus

    Directory of Open Access Journals (Sweden)

    V.I. Didenko

    2014-06-01

    Full Text Available The article deals with the morphological features of the liver tissue and changes in the metabolism of extracellular matrix components during progression of chronic hepatitis C. There has been carried out the comparison of computer morphometry of histological liver samples as an additional method of objectification of morphological study and and non-invasive markers of fibrosis.

  19. Wisconsin Card Sorting Test Performance in Relapsing-Remitting and Chronic-Progressive Multiple Sclerosis.

    Science.gov (United States)

    Rao, Stephen M.; And Others

    1987-01-01

    The Wisconsin Card Sorting Test (WCST), a measure of concept formation and set-shifting capacity, was administered to two groups of multiple sclerosis (MS) patients defined by clinical course. The chronic progressive patients achieved fewer conceptual categories due to significantly more perseverative responses than control patients, whereas the…

  20. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease

    DEFF Research Database (Denmark)

    Currie, Gemma; Taylor, Alison H M; Fujita, Toshiro

    2016-01-01

    BACKGROUND: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia...... is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. METHODS: We conducted a meta......-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators...

  1. Over 20 Years of Progress in Radiation Oncology: Seminoma.

    Science.gov (United States)

    Thomas

    1997-04-01

    During the past 20 years, significant changes have occurred in the management of seminoma. Survival has improved by approximately 10%, and now 97% of patients are cured. Reductions in the numbers of patients irradiated, the volumes irradiated, and the doses used should reduce morbidity. The 1973 Patterns of Care Study (PCS) and the planned new study proffer statements of consensus on optimal care and evaluate compliance with guidelines. Specific changes in investigation, including measurement of the serum tumor markers beta human choriaonic gonadotropin (betaHCG) and alphafetoprotein (AFP) and computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the retroperitoneum, better evaluate disease extent. For stage I disease, a reduction in the total dose of infradiaphragmatic irradiation to 2,500 cGy is recommended. An option for surveillance reduces unnecessary therapy in 80% and may improve fertility. The significance of disease bulk in stage II has been recognized, and treatment has been refined. The maximal radiation dose now recommended for stage II disease is 3,500 cGy. CT definition of radiation target volumes minimizes the risk of geographic miss. Prophylactic mediastinal irradiation is no longer recommended. Chemotherapy, usually now bleomycin, etoposide, and cisplatin, produces high cure rates for stage IID, IIImanagemetn. Controversy still surrounds optimal therapy for stage IIC disease. Unresolved questions include cost benefit and quality of life issues surrounding optimal management for stage I disease, inguinal scrotal irradiation in stage I and II disease, and identification of the least toxic but effective chemotherapy for specific subgroups of patients with advanced disease.

  2. Behavior, physiology, and energy deposition in rats chronically exposed to 2450-MHz radiation

    Energy Technology Data Exchange (ETDEWEB)

    D' Andrea, J.A.; Gandhi, O.P.

    1987-11-01

    The research program was initiated to determine both the specific absorption rate (SAR) and the behavioral and physiological consequences of chronic c-w microwave radiation exposure at 2450 MHz in the laboratory rat. Whole-body average and local SARs at discrete sites within the body of rats and mice were determined experimentally using different exposure systems and analytical techniques. The whole-body average SAR and the distribution of SAR within the body depends on a variety of factors: type of exposure system, polarization of the field, size of the animal, and angle of radiation incident on the body. Three experiments were conducted to determine the effects of chronic exposure to 2450-MHz microwave radiation on several measures of rat behavior and physiology. Groups of rats were exposed intermittently to 2450-MHz radiation at power densities of 0.5 mW/sq. cm. or 2.5 mW/sq. cm. for 90 days.

  3. Radiation physics, biophysics, and radiation biology. Progress report, December 1, 1993--November 30, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Hall, E.J.; Zaider, M.

    1994-05-01

    Research at the Center for Radiological Research is a blend of physics, chemistry and biology and epitomizes the multidisciplinary approach towards understanding the mechanisms involved in the health problems resulting from human exposure to ionizing radiations. To an increasing extent, the focus of attention is on biochemistry and the application of the techniques of molecular biology to the problems of radiation biology. Research highlights from the past year are briefly described.

  4. Silicon space solar cells: progression and radiation-resistance analysis

    Science.gov (United States)

    Rehman, Atteq ur; Lee, Sang Hee; Lee, Soo Hong

    2016-02-01

    In this paper, an overview of the solar cell technology based on silicon for applications in space is presented. First, the space environment and its effects on the basis of satellite orbits, such as geostationary earth orbit (GEO) and low earth orbit (LEO), are described. The space solar cell technology based on silicon-based materials, including thin-film silicon solar cells, for use in space was appraised. The evolution of the design for silicon solar cell for use in space, such as a backsurface field (BSF), selective doping, and both-side passivation, etc., is illustrated. This paper also describes the nature of radiation-induced defects and the models proposed for understanding the output power degradation in silicon space solar cells. The phenomenon of an anomalous increase in the short-circuit current ( I sc) in the fluence irradiation range from 2 × 1016 cm-2 to 5 × 1016 cm-2 is also described explicitly from the view point of the various presented models.

  5. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG; Yong; LI; Ming-chun; FU; Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation. Methods Animals were divided into three groups (n = 10), they were animals exposed to radiation (Rad), normal control animals (Ctr), and irradiated animals treated with LTN (Rad + LTN). Animal model of chronic radiation stress injury was induced by irradiating mice with 60 Co γ-ray for 6 weeks from Monday to Friday consecutively. Before radiation, the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL), whereas mice in other groups were injected with 0.9% physiological saline. The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen. The cell numbers and viability of T lymphocytes, which were isolated from the spleen, were determined by Trypan blue staining. Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured. Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes, associated with reduced T lymphocytes viability and functions, and elevated NO production. Treatment with LTN significantly normalized the elevated NO production, and attenuated the negative outcomes resulting from radiation mentioned above. Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  6. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG Yong; LI Ming-chun; FU Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation.Methods Animals were divided into three groups (n =10),they were animals exposed to radiation (Rad),normal control animals (Ctr),and irradiated animals treated with LTN (Rad + LTN).Animal model of chronic radiation stress injury was induced by irradiating mice with 60Co γ-ray for 6 weeks from Monday to Friday consecutively.Before radiation,the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL),whereas mice in other groups were injected with 0.9% physiological saline.The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen.The cell numbers and viability of T lymphocytes,which were isolated from the spleen,were determined by Trypan blue staining.Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured.Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes,associated with reduced T lymphocytes viability and functions,and elevated NO production.Treatment with LTN significantly normalized the elevated NO production,and attenuated the negative outcomes resulting from radiation mentioned above.Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  7. Organizing pneumonia appearing in B-cell chronic leukemia malignancy progression - a case report.

    Science.gov (United States)

    Polaczek, Mateusz Marek; Zych, Jacek; Opoka, Lucyna; Maksymiuk, Beata; Roszkowski-Sliż, Kazimierz

    2015-01-01

    Patients with chronic lymphocytic leukemia or non-Hodgkin’s lymphoma are at risk of infectious diseases of respiratory system because of immunodeficiency. Occurrence of organizing pneumonia in leukemic patients is most commonly correlated with bone marrow transplant or treatment with antimitotic agents. There have been only four reported cases of organizing pneumonia related solitarily to leukemia or lymphoma. We present a case of 65-year old gentlemen, diagnosed 8 months earlier with B-cell chronic lymphocytic leukemia with no previous hematologic treatment, who presented symptoms of persistent pneumonia with no significant reaction to antibiotics. Chest computed tomography scans showed well-localized consolidation with ground glass opacities and some air bronchogram, suggesting infectious disease. All results of microbiological examinations were negative. Due to radiological progression of parenchymal consolidation despite two intravenous courses of antibiotics open lung biopsy was performed. The histologic examination of lung specimen revealed structures typical for organizing pneumonia pattern. There was no evidence for leukemic involvement in lung tissue, as no sign for infectious factors from histological staining was observed. In the inferior mediastinal lymph node sample progression of chronic lymphatic leukemia to mixed cell lymphoma was diagnosed. Patient was commenced on prednisone 60 mg/daily with fast improvement. We believe that this is the first case of organizing pneumonia as a reaction to the conversion of B-cell chronic lymphocytic leukemia progression to more malignant stage.

  8. Radiation physics, biophysics, and radiation biology. Progress report, December 1, 1992--November 30, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Hall, E.J.; Zaider, M.

    1993-05-01

    Research at the Center for Radiological Research is a multidisciplenary blend of physics, chemistry and biology aimed at understanding the mechanisms involved in the health problems resulting from human exposure to ionizing radiations. The focus is increased on biochemistry and the application of the techniques of molecular biology to the problems of radiation biology. Research highlights of the program from the past year are described. A mathematical model describing the production of single-strand and double-strand breaks in DNA as a function radiation quality has been completed. For the first time Monte Carlo techniques have been used to obtain directly the spatial distribution of DNA moieties altered by radiation. This information was obtained by including the transport codes a realistic description of the electronic structure of DNA. We have investigated structure activity relationships for the potential oncogenicity of a new generation of bioreductive drugs that function as hypoxic cytotoxins. Experimental and theoretical investigation of the inverse dose rate effect, whereby medium LET radiations actually produce an c effect when the dose is protracted, is now at a point where the basic mechanisms are reasonably understood and the complex interplay between dose, dose rate and radiation quality which is necessary for the effect to be present can now be predicted at least in vitro. In terms of early radiobiological damage, a quantitative link has been established between basic energy deposition and locally multiply damaged sites, the radiochemical precursor of DNA double strand breaks; specifically, the spatial and energy deposition requirements necessary to form LMDs have been evaluated. For the first time, a mechanically understood ``biological fingerprint`` of high-LET radiation has been established. Specifically measurement of the ratio of inter-to intra-chromosomal aberrations produces a unique signature from alpha-particles or neutrons.

  9. Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Liliana SC Mendes; Marcelo E Nita; Suzane K Ono-Nita; Evandro S Mello; Luiz Caetano da Silva; Ven(a)ncio AF Alves; Flair J Carrilho

    2008-01-01

    AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies.METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised.Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System.RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease.The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22+0.50 vs -0.15 ± 0.46, P = 0.0053).Immuno-expression of interferon receptor is not a relevant factor.CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis.Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients.

  10. Morphologic MRI features, diffusion tensor imaging and radiation dosimetric analysis to differentiate pseudo-progression from early tumor progression.

    Science.gov (United States)

    Agarwal, Ajay; Kumar, Sanath; Narang, Jayant; Schultz, Lonni; Mikkelsen, Tom; Wang, Sumei; Siddiqui, Sarmad; Poptani, Harish; Jain, Rajan

    2013-05-01

    Pseudo-progression (PsP) refers to the paradoxical increase of contrast enhancement within 12 weeks of chemo-radiation therapy in gliomas attributable to treatment effects rather than early tumor progression (ETP). This study was performed to evaluate the utility of morphologic imaging features, diffusion tensor imaging (DTI) and radiation dosimetric analysis of magnetic resonance imaging (MRI) changes in differentiating PsP from ETP. Serial MRI examinations of 163 patients treated for high-grade glioma were reviewed. 46 patients showed a recurrent or progressive enhancing lesion within 12 weeks of radiotherapy. We used an in-house modified scoring system based on 20 different morphologic features (modified VASARI features) to assess the MRI studies. DTI analyses were performed in 24 patients. MRI changes were defined as recurrent volume (Vrec) and registered with pretreatment computed tomography dataset, and the actual dose received by the Vrec during treatment was calculated using dose-volume histograms. Bidimensional product of T2-FLAIR signal abnormality and enhancing component was larger in the ETP group. DTI metrics revealed no significant difference between the two groups. There was no statistically significant difference in the location of Vrec between PsP and ETP groups. Morphologic MRI features and DTI have a limited role in differentiating between PsP and ETP. The larger sizes of the T2-FLAIR signal abnormality and the enhancing component of the lesion favor ETP. There was no correlation between the pattern of MRI changes and radiation dose distribution between PsP and ETP groups.

  11. [Endolacunar laser radiation of the tonsils in conservative treatment of chronic tonsillitis].

    Science.gov (United States)

    Staroverova, T K; Shul'diakov, V A; Raĭgorodskiĭ, Iu M; Tatarenko, D A

    2007-01-01

    Vegetative and immune system indices, clinical symptoms of chronic tonsillitis exacerbation were compared in laser radiation of the tonsils with two methods - surface pharyngeal and endolacunar. The results show that under endolacunar method the symptoms regress 1.46 times faster, the number of late exacerbations decrease 1.5-2-fold.

  12. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats.

    Science.gov (United States)

    Zhu, Yongjun; Cui, Hongwang; Xia, Yunfeng; Gan, Hua

    2016-01-01

    Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL-positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD.

  13. miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia.

    Science.gov (United States)

    Visone, Rosa; Veronese, Angelo; Rassenti, Laura Z; Balatti, Veronica; Pearl, Dennis K; Acunzo, Mario; Volinia, Stefano; Taccioli, Cristian; Kipps, Thomas J; Croce, Carlo M

    2011-09-15

    MicroRNAs play a crucial role in chronic lymphocytic leukemia. We investigated whether microRNAs can discriminate patients with a progressive disease from patients with a stable disease. We analyzed microRNA expression on leukemic cells isolated from 358 sequential samples of 114 patients with either stable or progressive disease. We found that during the course of the disease the expression values of miR-181b, the most dysregulated microRNA, decreased in samples of patients with a progressive (P miR-181b value ≤ 0.005 at the starting time point were significant to differentiate progressive from stable disease (P = .004, training set; P miR-181b targets Mcl-1 protein and that the decrease of its expression inversely correlated with increased protein levels of MCL1 and BCL2 target genes. We conclude that parameters defined on the basis of the miR-181b expression values specify disease progression in chronic lymphocytic leukemia and are associated with clinical outcome.

  14. A case of biopsy-proven chronic kidney disease on progression from acute phosphate nephropathy

    Directory of Open Access Journals (Sweden)

    Woo Chul Joo

    2012-06-01

    Full Text Available Acute phosphate nephropathy (APhN following oral sodium phosphate solution (OSP ingestion as a bowel purgative has been frequently reported. It was recently suggested that APhN could progress to chronic kidney disease (CKD and a history of APhN might be considered as one of the causes of CKD. However, there are few reports proving APhN as a cause of CKD. Here, we report a case of APhN that progressed to CKD, as proven by renal biopsy.

  15. Crosstalk between the unfolded protein response and NF-κB-mediated inflammation in the progression of chronic kidney disease.

    Science.gov (United States)

    Mohammed-Ali, Zahraa; Cruz, Gaile L; Dickhout, Jeffrey G

    2015-01-01

    The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation.

  16. Uraemia progression in chronic kidney disease stages 3-5 is not constant

    DEFF Research Database (Denmark)

    Heaf, James Goya; Mortensen, Leif Spange

    2011-01-01

    Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m(2)/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimat...... GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating....

  17. Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Claudia; Paternostro; Ezio; David; Erica; Novo; Maurizio; Parola

    2010-01-01

    Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,th...

  18. Recent progress of the RD50 Collaboration – Development of radiation tolerant tracking detectors

    CERN Document Server

    Moll, M

    2014-01-01

    The CERN RD50 Collaboration "Radiation hard semiconductor devices for high luminosity col- liders" is undertaking a massive R&D; programme across High Energy Physics (HEP) Experi- ments boundaries to develop silicon sensors with increased radiation tolerance. Highest priority is to provide concepts and prototypes of high performance silicon sensors for the High-Luminosity Large Hadron Collider (HL-LHC) Experiments at CERN and other future HEP Experiments op- erating in severe radiation environments. This paper gives an overview of the RD50 collaboration activities and describes some examples of recent developments. Emphasis is put on the charac- terization of microscopic radiation induced defects and their impact on the sensor performance, the evaluation and parametrization of electric fields inside irradiated sensors, progress in device modeling using TCAD tools, the use of p-type silicon as strip and pixel sensor material and finally the first steps towards the exploitation of impact ionization ( charge...

  19. Molecular events basic to cellular radiation response. Progress report, July 1, 1976--September 30, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Kolodny, G.M.

    1977-01-01

    Progress is reported on studies of the effects of x irradiation at the cellular level that lead ultimately to either malignant transformation or cell death. Experimental results consistent with the primer hypothesis for the regulation of gene expression in eukaryotes are reported. It was found that oligonucleotides can be inserted en bloc into newly synthesized RNA. Studies on amino acid-nucleic acid interactions were continued by successfully synthesizing an amidate and beginning NMR studies on the interactions between its nucleic acid and amino acid moieties. In studies on radiation induced giant cells in 3T3 cells growing in culture, it was demonstrated that conditions which potentiate potential lethal damage repair and those which prevent radiation induced giant cell formation exist. In an examination of the in vitro effects of vasopressin, no direct effect was found of vasopressin on radiation sensitivity and significant effects of radiation on lysosomal enzyme activity in cultured cells were found.

  20. Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE

    DEFF Research Database (Denmark)

    Renno, T; Taupin, V; Bourbonnière, L;

    1998-01-01

    The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes....... In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS....... IFNgamma therefore may play a role in chronic demyelination and long-term disability following the induction of demyelinating disease. Because IFNgamma may have neural as well as immune-infiltrating origins, these findings generate a new perspective on its role in the CNS....

  1. Chronic low-dose radiation protects cells from high-dose radiation via increase of AKT expression by NF-{sub k}B

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyung Sun; Seong, Ki Moon; Kim, Ji Young; Kim, Cha Soon; Yang, Kwang Hee; Nam, Seon Young [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., LTD., Gyeongju (Korea, Republic of)

    2013-04-15

    Exposure to low-dose and low-dose rate of ionizing radiation is an important issue in radiation protection. Low-dose ionizing radiation has been observed to elicit distinctly different responses compared to high-dose radiation, in various biological systems including the reproductive, immune, and hematopoietic systems (Liu et al. 2006). Some data were reported that low-dose radiation could initiate beneficial effects by stimulating cell growth, DNA repair, activation of transcription factors and gene expression (Calabrese et al., 2004). Cells exposed to low-dose radiation can develop adaptive resistance to subsequent high-dose radiation induced DNA damage, gene mutation, and cell death. We previously reported that low-dose of ionizing radiation induced cell survival through the activation of AKT (protein kinase B, PKB) pathway (Park et al., 2009). AKT has been shown to be potently activated in response to a wide variety of growth factors and ionizing radiation. Cell survival against ionizing radiation seems to be associated with the activation of AKT pathway via phosphorylation of its downstream nuclear target molecules. In the present study, we examined the effects of chronic low-dose irradiation in human lung fibroblast cells. The aim was to explore the possibility of a low-dose radiation-induced adaptive cellular response against subsequent challenging high-dose irradiation. In the present study, we examined the regulatory mechanism responsible for cellular response induced by chronic low-dose of ionizing radiation in normal human cells. We found that the level of AKT protein was closely associated with cell survival. In addition, NF-{sub k}B activation by chronic low-dose radiation regulates AKT activation via gene expression and acinus expression. In conclusion, our data demonstrate that chronic low-dose radiation could inhibit the cell death induced by cytotoxic high-dose radiation through the modulation of the level of AKT and acinus proteins via NF-{sub k

  2. Comment on "Recent progress in thermodynamics of radiation - exergy of radiation, effective temperature of photon and entropy constant of photon"

    Institute of Scientific and Technical Information of China (English)

    LIU LinHua

    2009-01-01

    Chen et al. proposed the concepts of effective temperature of photon and entropy constant of photon in a recent paper [Chen Z S, Mo S P, Hu P. Recent progress in thermodynamics of radiation-exergy of radiation, effective temperature of photon and entropy constant of photon. Sci China Ser E-Tech Sci,2008, 51(8): 1096-1109] by enduing a single photon with macroscale thermodynamic parameters such as exergy and entropy. This paper argues that applying these concepts and their inferences to macro-scale thermodynamic system will lead to the results which conflict with macroscale thermodynamic laws. This means that the concepts of effective temperature of photon and entropy constant of photon are not correct.

  3. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  4. Analysis of chronic radiation exposure at small doses

    Energy Technology Data Exchange (ETDEWEB)

    Krestinina, L.Y. [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation)

    2000-05-01

    The purpose of the study was to analyze the late effects of radiation exposure among residents of settlements located on the territory of the East-Urals Radiation Trace (EURT) in the Southern Urals. In 1957 an explosion occurred at the depot of radioactive waste in the Southern Urals. An area of 23000 km{sup 2} was contaminated, with contamination density of over 0.1 Ci/m{sup 2} for {sup 90}Sr. There were 217 populated ares on that territory with total population about 270000. The residents of 22 villages with contamination density of over 4 Ci/km{sup 2} for {sup 90}Sr were evacuated. The times of evacuation differed from 7 to 670 days since the accident, depending on the level of contamination. In 1988-1993 an individualized registry was created at the Urals Research Center for Radiation Medicine (URCRM) which included information on the residents of 22 evacuated villages and a proportion of unevacuated residents of the EURT area. Currently, the registry contains data on 30000 residents. Of that number 17000 persons were born before, and 12000 after the accident (including about 9000 offspring of exposed residents evacuated from the EURT, and about 3000 persons who were born after the accident and have been living permanently in the EURT area). Over the 35-year period since the accident the residents have received mean effective doses ranging from 23 to 530 mSv. The mean effective doses received by permanent residents range from 5 to 60 mSv. The cohort of people exposed on the EURT territory was identified based on the information contained in the registry. If a person happened to be in the EURT area at the time of the accident, he/she was considered to be eligible for inclusion in the cohort. Over the 35-year period (from 1957 through 1992) 29.5% of 17872 residents died, and 35% of the original cohort were lost to follow-up for different reasons. To enable an analysis a control group was established which included residents of villages located outside, but close

  5. Reaction of fresh water zooplankton community to chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Osipov, D.; Pryakhin, E. [Urals Research Center for Radiation Medicine - URCRM (Russian Federation); Ivanov, I. [FSUE Mayak PA (Russian Federation)

    2014-07-01

    The characteristic features of ecological community as a whole and cenosis of zooplankton organisms as part of it determine the intensity of the processes of self-purification of water and the formation of a particular body of water. Identifying features of the structure and composition of the zooplankton community of aquatic ecosystems exposed to different levels of radiation exposure, it is necessary to identify patterns of changes in zooplankton and hydro-biocenosis as a whole. Industrial reservoirs, the storage of liquid low-level radioactive waste 'Mayak' for decades, have high radiation load. A large range of levels of radioactive contamination (total volume beta-activity in water varies from 2.2x10{sup 3} to 2.3x10{sup 7} Bq/l, total volume alpha-activity - from 2.6x10{sup -1} to 3.1x10{sup 3} Bq/l) provides a unique opportunity to study ecosystems in a number of reservoirs with increasing impact of radiation factor. We studied five reservoirs that were used as the storage of low-and intermediate-level liquid radioactive waste pond and one comparison water body. In parallel with zooplankton sampling water samples were collected for hydro-chemical analysis. 41 indicators were analysed in order to assess the water chemistry. To determine the content of radionuclides in the various components of the ecosystem samples were collected from water, bottom sediments and plankton. Sampling of zooplankton for the quantitative analysis was performed using the method of weighted average auto bathometer. Apshteyn's plankton net of the surface horizon was used for qualitative analysis of the species composition of zooplankton. Software package ERICA Assessment Tool 2012 was used for the calculation of the absorbed dose rate. Species diversity and biomass of zooplankton, the share of rotifers in the number of species, abundance and biomass decrease with the increase of the absorbed dose rate and salinity. The number of species in a sample decreases with the

  6. Modeling hematopoietic system response caused by chronic exposure to ionizing radiation.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2011-05-01

    A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950-1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose-effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).

  7. Lower thresholds for lifetime health effects in mammals from high-LET radiation - Comparison with chronic low-LET radiation.

    Science.gov (United States)

    Sazykina, Tatiana G; Kryshev, Alexander I

    2016-12-01

    Lower threshold dose rates and confidence limits are quantified for lifetime radiation effects in mammalian animals from internally deposited alpha-emitting radionuclides. Extensive datasets on effects from internal alpha-emitters are compiled from the International Radiobiological Archives. In total, the compiled database includes 257 records, which are analyzed by means of non-parametric order statistics. The generic lower threshold for alpha-emitters in mammalian animals (combined datasets) is 6.6·10(-5) Gy day(-1). Thresholds for individual alpha-emitting elements differ considerably: plutonium and americium - 2.0·10(-5) Gy day(-1); radium - 2.1·10(-4) Gy day(-1). Threshold for chronic low-LET radiation is previously estimated at 1·10(-3) Gy day(-1). For low exposures, the following values of alpha radiation weighting factor wR for internally deposited alpha-emitters in mammals are quantified: wR(α) = 15 as a generic value for the whole group of alpha-emitters; wR(Pu) = 50 for plutonium; wR(Am) = 50 for americium; wR(Ra) = 5 for radium. These values are proposed to serve as radiation weighting factors in calculations of equivalent doses to non-human biota. The lower threshold dose rate for long-lived mammals (dogs) is significantly lower than comparing with the threshold for short-lived mammals (mice): 2.7·10(-5) Gy day(-1), and 2.0·10(-4) Gy day(-1), respectively. The difference in thresholds is exactly reflecting the relationship between the natural longevity of these two species. Graded scale of severity in lifetime radiation effects in mammals is developed, based on compiled datasets. Being placed on the severity scale, the effects of internal alpha-emitters are situated in the zones of considerably lower dose rates than effects of the same severity caused by low-LET radiation. RBE values, calculated for effects of equal severity, are found to depend on the intensity of chronic exposure: different RBE values are characteristic for low

  8. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  9. Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.

    Science.gov (United States)

    Hahm, C; Huh, H J; Mun, Y C; Seong, C M; Chung, W S; Huh, J

    2015-04-01

    Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) may transform into secondary myelofibrosis (MF) or evolve into acute myeloid leukemia (AML). The genetic mechanisms underlying disease progression in MPN and MDS/MPN patients remain unclear. The purpose of this study was to investigate sequential genomic aberrations identified by single nucleotide polymorphism array (SNP-A)-based karyotyping that can detect cryptic aberrations or copy neutral loss of heterozygosity (CN-LOH) in the chronic phase and during disease progression of MPN and MDS/MPN patients. The study group included 13 MPN and four MDS/MPN patients (seven polycythemia vera (PV); four essential thrombocythemia (ET); two MPN-unclassifiable (MPN-U); one chronic myelomonocytic leukemia (CMML); one atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML); and two MDS/MPN-unclassifiable (MDS/MPN-U)). Among them, five patients (two PV, two MPN-U, and one MDS/MPN-U) progressed to MF and three patients (one CMML, one aCML, and one MDS/MPN-U) transformed to AML. The median follow-up period was 70 months (range, 7-152). Whole-genome SNP-A (SNP 6.0; Affymetrix, Santa Clara, CA, USA)-based karyotyping and JAK2 mutation analysis were performed according to the manufacturer's instructions. SNP-A showed 19 kinds of genomic aberrations, including seven gains, eight deletions, and four CN-LOH. CN-LOH of 9p involving JAK2 was the most common aberration, followed by 5q deletion and 9p gain. The incidence of genomic changes identified by SNP was not different in patients with disease progression (75%), compared with those without disease progression (56%) (P = 0.4). However, when excluding 9p CN-LOH, the incidence of genomic changes was significantly higher in patients with disease progression than in patients without disease progression (63% and 0%, respectively, P = 0.01). Among eight patients with disease progression, two patients (two MPN-U) showed abnormal SNP-A results

  10. A review of progress towards understanding the transient global mean surface temperature response to radiative perturbation

    Science.gov (United States)

    Yoshimori, Masakazu; Watanabe, Masahiro; Shiogama, Hideo; Oka, Akira; Abe-Ouchi, Ayako; Ohgaito, Rumi; Kamae, Youichi

    2016-12-01

    The correct understanding of the transient response to external radiative perturbation is important for the interpretation of observed climate change, the prediction of near-future climate change, and committed warming under climate stabilization scenarios, as well as the estimation of equilibrium climate sensitivity based on observation data. It has been known for some time that the radiative damping rate per unit of global mean surface temperature increase varies with time, and this inconstancy affects the transient response. Knowledge of the equilibrium response alone is insufficient, but understanding the transient response of the global mean surface temperature has made rapid progress. The recent progress accompanies the relatively new concept of the efficacies of ocean heat uptake and forcing. The ocean heat uptake efficacy associates the temperature response induced by ocean heat uptake with equilibrium temperature response, and the efficacy of forcing compares the temperature response caused by non-CO2 forcing with that by CO2 forcing.

  11. Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice.

    Science.gov (United States)

    Rogers, Arlin B; Boutin, Samuel R; Whary, Mark T; Sundina, Nataliya; Ge, Zhongming; Cormier, Kathleen; Fox, James G

    2004-01-01

    Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.

  12. Gene polymorphisms of renin-angiotensin-aldosterone system components and the progression of chronic kidney diseases

    Directory of Open Access Journals (Sweden)

    Agata Kujawa-Szewieczek

    2010-08-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D, angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms.A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy.The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. Conclusion: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis.Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

  13. Dietary Energy Density, Renal Function, and Progression of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Rouhani

    2016-01-01

    Full Text Available Background. There is evidence of the association between dietary energy density and chronic diseases. However, no report exists regarding the relation between DED and chronic kidney disease (CKD. Objective. To examine the association between dietary energy density (DED, renal function, and progression of chronic kidney disease (CKD. Design. Cross-sectional. Setting. Three nephrology clinics. Subjects. Two hundred twenty-one subjects with diagnosed CKD. Main Outcome Measure. Dietary intake of patients was assessed by a validated food frequency questionnaire. DED (in kcal/g was calculated with the use of energy content and weight of solid foods and energy yielding beverages. Renal function was measured by blood urea nitrogen (BUN, serum creatinine (Cr, and estimated glomerular filtration rate (eGFR. Results. Patients in the first tertile of DED consumed more amounts of carbohydrate, dietary fiber, potassium, phosphorus, zinc, magnesium, calcium, folate, vitamin C, and vitamin B2. After adjusting for confounders, we could not find any significant trend for BUN and Cr across tertiles of DED. In multivariate model, an increased risk of being in the higher stage of CKD was found among those in the last tertile of DED (OR: 3.15; 95% CI: 1.30, 7.63; P=0.01. Conclusion. We observed that lower DED was associated with better nutrient intake and lower risk of CKD progression.

  14. Dietary Energy Density, Renal Function, and Progression of Chronic Kidney Disease

    Science.gov (United States)

    Rouhani, Mohammad Hossein; Najafabadi, Mojgan Mortazavi; Esmaillzadeh, Ahmad; Feizi, Awat

    2016-01-01

    Background. There is evidence of the association between dietary energy density and chronic diseases. However, no report exists regarding the relation between DED and chronic kidney disease (CKD). Objective. To examine the association between dietary energy density (DED), renal function, and progression of chronic kidney disease (CKD). Design. Cross-sectional. Setting. Three nephrology clinics. Subjects. Two hundred twenty-one subjects with diagnosed CKD. Main Outcome Measure. Dietary intake of patients was assessed by a validated food frequency questionnaire. DED (in kcal/g) was calculated with the use of energy content and weight of solid foods and energy yielding beverages. Renal function was measured by blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). Results. Patients in the first tertile of DED consumed more amounts of carbohydrate, dietary fiber, potassium, phosphorus, zinc, magnesium, calcium, folate, vitamin C, and vitamin B2. After adjusting for confounders, we could not find any significant trend for BUN and Cr across tertiles of DED. In multivariate model, an increased risk of being in the higher stage of CKD was found among those in the last tertile of DED (OR: 3.15; 95% CI: 1.30, 7.63; P = 0.01). Conclusion. We observed that lower DED was associated with better nutrient intake and lower risk of CKD progression. PMID:27819022

  15. Progressive tumefactive fibroinflammatory lesion of the infratemporal fossa treated by radiation therapy

    Directory of Open Access Journals (Sweden)

    Brian O’Sullivan

    2012-01-01

    Full Text Available Tumefactive fibroinflammatory lesion (TFIL is a rare benign tumor in the head and neck region. We present a case of a 40-year-old female with a benign but progressive lesion of the infratemporal fossa, which was diagnosed as TFIL. Patient responded briefly to a course of steroid treatment but eventually showed progression and was unresponsive to further steroids. She was then treated with external beam radiation to a dose of 60 Gy in 30 fractions. After radiation a slow, gradual decrease in tumor size was noted over the course of years and she is free of disease after more than 11 years of follow-up. The major longterm side effect this patient developed was an expected unilateral radiation-induced retinopathy, due to the close proximity of the lesion to the orbit. The dilemma of treatment of benign disease with radiation with potential long-term complications is discussed and a review of the literature on TFIL is presented.

  16. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and rh

  17. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and

  18. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

    DEFF Research Database (Denmark)

    Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L;

    1995-01-01

    /I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...

  19. Effect of enalapril on the progression of chronic renal failure. A randomized controlled trial

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Leyssac, P P

    1992-01-01

    In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril or conve......In order to study the influence of angiotensin converting enzyme (ACE) inhibition on the progression of chronic nephropathy, 70 patients with a median glomerular filtration rate (GFR) of 15 (range, 6 to 54) mL/min/1.73 m2 were randomized in an open study to basic treatment with enalapril....... The therapeutic goal was a BP of 120 to 140/80 to 90 mm Hg. The GFR, estimated by the plasma clearance of 51Cr-EDTA, was measured every third month, and the individual rate of progression was calculated as the slope of the GFR v time plot. In the enalapril group, the median decline in GFR was -0.20 (range, +0...

  20. Effect of stem cells seeded onto biomaterial on the progression of experimental chronic kidney disease.

    Science.gov (United States)

    Caldas, Heloisa C; Fernandes, Ida M M; Kawasaki-Oyama, Rosa S; Baptista, Maria Alice S F; Plepis, Ana Maria G; Martins, Virginia A; Coimbra, Terezila M; Goloni-Bertollo, Eny M; Braile, Domingo M; Abbud-Filho, Mario

    2011-06-01

    Different routes for the administration of bone marrow-derived cells (BMDC) have been proposed to treat the progression of chronic renal failure (CRF). We investigated whether (1) the use of bovine pericardium (BP) as a scaffold for cell therapy would retard the progression of CRF and (2) the efficacy of cell therapy differently impacts distinct degrees of CRF. We used 2/3 and 5/6 models of renal mass reduction to simulate different stages of chronicity. Treatments consisted of BP seeded with either mesenchymal or mononuclear cells implanted in the parenchyma of remnant kidney. Renal function and proteinuria were measured at days 45 and 90 after cell implantation. BMDC treatment reduced glomerulosclerosis, interstitial fibrosis and lymphocytic infiltration. Immunohistochemistry showed decreased macrophage accumulation, proliferative activity and the expression of fibronectin and α-smooth muscle-actin. Our results demonstrate: (1) biomaterial combined with BMDC did retard the progression of experimental CRF; (2) cellular therapy stabilized serum creatinine (sCr), improved creatinine clearance and 1/sCr slope when administered during the less severe stages of CRF; (3) treatment with combined therapy decreased glomerulosclerosis, fibrosis and the expression of fibrogenic molecules; and (4) biomaterials seeded with BMDC can be an alternative route of cellular therapy.

  1. PROGRESSIVE MUSCLE RELAXATION INCREASE PEAK EXPIRATORY FLOW RATE ON CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS

    Directory of Open Access Journals (Sweden)

    Tintin Sukartini

    2017-07-01

    Full Text Available Introduction: Limited progressive air flow in Chronic Obstructive Pulmonary Disease (COPD can caused by small airway disease (bronchiolitis obstructive and loss of elasticity of the lung (emphysema. Further it can be decreasing the quality of life in COPD patients because dyspnea and uncomfortable in activity. Progressive muscle relaxation (PMR is one of the relaxation technique that can repair pulmonary ventilation by decreasing chronic constriction of the respiratory muscles. The objective of this study was to analyze the effect of progressive muscle relaxation on raised peak expiratory flow rate (PEFR. Method: A pre-experimental one group pre-post test design was used in this study. Population was all of the COPD patients at Pulmonary Specialist Polyclinic Dr Mohamad Soewandhie Surabaya. There were 8 respondents taken by using purposive sampling. PEFR was counted by using peak flow meter every six day. Data were analyzed by using Paired t-Test with significance level  p≤0.05. Result: The result showed that PMR had significance level on increasing of PEFR (p=0.012. Discussion: It can be concluded that PMR has an effect on raise PEFR. Further studies are recommended to measure the effect of PMR on respiratory rate (RR, heart rate (HR subjective dyspnoe symptoms, forced expiration volume on the first minute (FEV1 and mid maximum flow rate (MMFR in COPD patients.

  2. Radiation damage and repair in cells and cell components. Progress report, November 1, 1977--October 31, 1978. [Uv and x radiation, bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Fluke, D.J.; Pollard, E.C.

    1978-01-01

    Progress is reported on the following research projects: coordinate induction of mutagenesis, radioresistance, and inhibition of post-radiation DNA degradation; radioinduced filamentation; action spectrum for induction of K12 lambda phage; effects of uv radiation on cells in the frozen state; dependence of mutagenesis on wavelength of uv; and w-reactivation of x-irradiated phage lambda. (HLW)

  3. Structured approach to design of diagnostic test evaluation studies for chronic progressive infections in animals.

    Science.gov (United States)

    Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew

    2011-05-12

    Diagnostic test evaluations (DTEs) for chronic infections are challenging because a protracted incubation period has to be considered in the design of the DTE, and the adverse effects of infection may be widespread and progressive over an animal's entire life. Frequently, the specific purpose of the test is not formally considered when a test is evaluated. Therefore, the result is often a DTE where test sensitivity and specificity estimates are biased, either because of problems with establishing the true infection status or because the test detects another aspect of the infection (and analyte) than originally intended. The objective of this paper is to outline a structured approach to the design and conduct of a DTE for diagnostic tests used for chronic infections in animals, and intended for different purposes. We describe the process from reflections about test purpose and the underlying target condition through considerations of the pathogenesis, and specification of a practical case definition, which can subsequently be used in the DTE for the specific purpose. The process is illustrated by two examples of Mycobacterium avium subsp. paratuberculosis (MAP) infections in cattle. MAP infections are chronic and can result in different adverse effects at different time points during the incubation period. The description provides input on the process and deductive reasoning which are integral parts to develop a high-quality design of a DTE for chronic infectious diseases.

  4. Mitigating preventable chronic disease: Progress report of the Cleveland Clinic's Lifestyle 180 program

    Directory of Open Access Journals (Sweden)

    Ricanati Elizabeth HW

    2011-11-01

    Full Text Available Abstract Background Poor lifestyle choices are key in development and progression of preventable chronic diseases. The purpose of the study was to design and test a program to mitigate the physical and fiscal consequences of chronic diseases. Methods Here we report the outcomes for 429 participants with one or more chronic conditions, including obesity, hypertension, hyperlipidemia and diabetes mellitus, many of whom had failed traditional disease management programs, who enrolled into a comprehensive lifestyle intervention. The Lifestyle 180 program integrates nutrition, physical activity and stress management interventions and was conducted at the Wellness Institute of the Cleveland Clinic, United States. An intensive 6 week immersion course, with 8 hours of group instruction per week, was followed by 3 follow-up, 4 hour-long sessions over the course of 6 months. Results Changes in biometric (weight, height, waist circumference, resting heart rate and blood pressure and laboratory variables (fasting lipid panel, blood glucose, insulin, hemoglobin A1c, ultra sensitive C-reactive protein at 6 months were compared with baseline (pre-post analysis. At week 30, biometric and laboratory data were available for 244 (57% and 299 (70% participants, respectively. These had a mean ± SD reduction in weight (6.8 ± 6.9 kg, P Conclusion Implementation of a comprehensive lifestyle modification program among adults with common chronic conditions results in significant and clinically meaningful improvements in biometric and laboratory outcomes after 6 months.

  5. Analysis of Chronic Radiation Sickness Cases in the Population of the Southern Urals

    Science.gov (United States)

    1994-08-01

    radiation were conducted as part of this study, which is a detailed retrospective review of the effects of exposures resulting from either accidental or...chronic coronary number of segmented neutrophils. The number of insufficiency and cerebrovascular sclerosis in 1972; reticular cells, plasmatic cells...osteomuscular system 4 Heart diseases of pulmonary origin 25 Osteomyelitis 4 Ischemic heart disease 10 Cerebrovascular diseases 12 Trauma 22

  6. A novel biomarker of laminin turnover is associated with mortality and disease progression in chronic kidney disease

    DEFF Research Database (Denmark)

    Nielsen, Signe Holm; Guldager Kring Rasmussen, Daniel; Fenton, Anthony

    2017-01-01

    INTRODUCTION AND AIMS: Patients with chronic kidney disease (CKD) have increased risk of progressing to end-stage renal disease (ESRD) and a high mortality rate. One of the major underlying causes of progression of renal failure is renal fibrosis, which is caused by dysregulated extracellular...

  7. Current and future disease progression of the chronic HCV population in the United States.

    Science.gov (United States)

    Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

    2013-01-01

    Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  8. Current and future disease progression of the chronic HCV population in the United States.

    Directory of Open Access Journals (Sweden)

    Martin Zalesak

    Full Text Available Chronic hepatitis C virus (HCV infection can lead to advanced liver disease (AdvLD, including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009. We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  9. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1996-01-01

    fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P .... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  10. Rapidly progressing, massive mitral annular calcification. Occurrence in a patient with chronic renal failure.

    Science.gov (United States)

    Depace, N L; Rohrer, A H; Kotler, M N; Brezin, J H; Parry, W R

    1981-11-01

    Calcification of the mitral annulus developed in a patient while undergoing dialysis. The rapid onset of events corresponded to the onset of end-stage renal failure and uncontrolled secondary hyperparathyroidism. Sequential echocardiograms verified the progression of calcification of the annulus as well as the valve. A new systolic and diastolic murmur and reduced valve orifice on two-dimensional echocardiography suggested acquired nonrheumatic mitral stenosis and insufficiency. We propose that metastatic calcium deposition rather than long-term hypertensive and degenerative effects was the predominant mechanism for massive calcification of the annulus and valve. It is suggested that M-mode echocardiography be used sequentially to follow both the occurrence and progression of calcification of the mitral annulus or valve in patients with chronic renal failure, secondary hyperparathyroidism, or both.

  11. MiR-181b: new perspective to evaluate disease progression in chronic lymphocytic leukemia.

    Science.gov (United States)

    Visone, Rosa; Veronese, Angelo; Balatti, Veronica; Croce, Carlo M

    2012-02-01

    Over the past decades numerous markers of the tumor burden have been discovered in chronic lymphocytic leukemia (CLL). Among these, the microRNAs seem to have a promising role. The development and validation of miRNAs as biomarkers should have significant impact in improving early cancer detection and diagnosis, enhancing therapeutic success, and increasing the life expectancy of patients. We identified miR-181b as a biomarker for the progression of this disease from indolent to aggressive. For this study we used sequential samples from patients with either progressive or stable course of the illness. Here, we discuss more extensively this issue by adding novel findings and introducing a novel approach for monitoring CLL patients.

  12. Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Yu Jin; Kim, Mi Sook; Jang, Won Il; Seo, Young Seok; Cho, Chul Koo; Yoo, Hyung Jun; Paik, Eun Kyung [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2017-06-15

    To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3–4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1–2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

  13. Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

    2016-11-14

    To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

  14. Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

    Science.gov (United States)

    Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

    2016-01-01

    AIM To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans. PMID:27895431

  15. Keratin 18 phosphorylation as a progression marker of chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Wu Hao

    2010-03-01

    Full Text Available Abstract Background The intermediate filament proteins keratins 18 (K18 and 8 (K8 polymerize to form the cytoskeletal network in the mature hepatocytes. It has been shown that the phosphorylation of K18 at two serine residues, 33 and 52, correlates with the progression of hepatitis C, but little is known of chronic hepatitis B (CHB. In this study, we examined K18 phosphorylation in relation to CHB. Results Site-specific phosphorylation of K18 was determined in livers of twelve healthy donors, and non-cirrhosis (n = 40 and cirrhosis (n = 21 patients. On average, progressively higher level of Ser52 phosphorylation was observed in non-cirrhotic and cirrhotic livers, while elevated Ser33 phosphorylation was detected in both livers but no significant difference. Progressive increase of Ser33 and Ser52 phosphorylation correlated with the elevation of both histological lesions and enzymatic activities of alanine aminotransferase in non-cirrhotic livers. In the hepatocytes of an inactive HBV carrier, strong signals of Ser33 phosphorylation were co-localized with viral infection, while only basal level of Ser52 phosphorylation was detected in infected cells. Conclusion Assuming all obtained data, our data suggest that K18 phosphorylation is a progression marker for CHB.

  16. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1982-04-01

    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

  17. [Chronic progressive external ophthalmoplegia with mitochondrial anomalies. Clinical, histological, biochemical and genetic analysis (9 cases)].

    Science.gov (United States)

    Drouet, A

    1996-01-01

    We report the clinical signs and histological findings in nine patients with mitochondrial ocular myopathies. There were four males and five females. Of age ranging from 47 to 82 years. A more often asymetrical ptosis was in all cases of chronic progressive external ophtalmoplegia (CPEO), but muscle weakness in limbs was not usual. The prognosis in this group was good, but ubidecarenone (150 mg/d) used for two cases, did not improve ophtalmoplegia. The serum creatine kinase was normal in eight of nine cases and electromyography showed myopathic changes in three cases. Histoenzymatic analysis of the muscle biopsy and biochemical studies of mitochondria isolated from the muscle sample demonstrated mitochondrial myopathy associated with partial deficiency of complexes I and/or IV of the electron transfer chain. One of seven patients studied had single deletion by Southern blot analysis, in a heteroplasmic state and another an A-->G transition at position 3243 within the mitochondrial tRNA leu (UUR) gene. Chronic progressive external ophtalmoplegia, without large deletion, may have abnormality in other coding regions of mt DNA such as tRNA, rRNA or protein genes.

  18. Effect of chronic alcohol ingestion on the progression of periodontitis induced in Fisher-344 rats

    Directory of Open Access Journals (Sweden)

    Éder Ricardo Biasoli

    2009-01-01

    Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.

  19. Effect of Rebamipide on the Premalignant Progression of Chronic Gastritis: A Randomized Controlled Study.

    Science.gov (United States)

    Han, Xue; Jiang, Kui; Wang, Bangmao; Zhou, Lu; Chen, Xin; Li, Shu

    2015-10-01

    Chronic gastritis frequently progresses into precancerous intestinal metaplasia and intraepithelial neoplasia lesions. Rebamipide is a free radical scavenger and we assessed its efficacy on clinical symptoms, gastric mucosal lesions, pathologic grade, and immunohistochemistry in chronic gastritis patients. 178 eligible patients were randomized into treatment and control groups. Both groups followed an optimized lifestyle for 26 weeks, but the treatment group was additionally medicated with rebamipide 0.1 g three times per day. Upper gastrointestinal endoscopy was performed in all patients to evaluate the severity of gastritis by the Modified Lanza Scoring (MLS) and histological changes were evaluated by the Updated Sydney System Score (USSS). Gastric mucosa immunohistochemistry in the treatment group was performed using the intestinal metaplasia markers caudal type homeobox transcription factor 2 (CDX2) and trefoil factor 3 (TFF3) detection. There were significant outcome differences between the treatment and control groups regarding the clinical symptom scores (2.62 ± 1.86 vs. 1.55 ± 1.61, P = 0.0001), gastric mucosal lesion scores (0.57 ± 1.05 vs. 0.16 ± 0.90, P = 0.002), and inflammation (P rebamipide medication than pre-treatment values. Rebamipide improved the clinical symptoms, gastric mucosal lesions, and pathological grades of chronic gastritis patients and decreased the expression rates of CDX2 and TFF3 in gastric cells.

  20. Radiation promotes malignant progression of glioma cells through HIF-1alpha stabilization.

    Science.gov (United States)

    Kim, Young-Heon; Yoo, Ki-Chun; Cui, Yan-Hong; Uddin, Nizam; Lim, Eun-Jung; Kim, Min-Jung; Nam, Seon-Young; Kim, In-Gyu; Suh, Yongjoon; Lee, Su-Jae

    2014-11-01

    Given its contribution to malignant phenotypes of cancer, tumor hypoxia has been considered as a potential therapeutic problem. In the stressful microenvironment condition, hypoxia inducible factor 1 (HIF1) is well known to mediate the transcriptional adaptation of cells to hypoxia and acts as a central player for the process of hypoxia-driven malignant cancer progression. Here, we found that irradiation causes the HIF1α protein to stabilize, even in normoxia condition through activation of p38 MAPK, thereby promoting angiogenesis in tumor microenvironment and infiltrative property of glioma cells. Notably, irradiation reduced hydroxylation of HIF1α through destabilization of prolyl hydroxylases (PHD)-2. Moreover, radiation also decreased the half-life of protein von Hippel-Lindau (pVHL), which is a specific E3 ligase for HIF1α. Of note, inhibition of p38 MAPK attenuated radiation-induced stabilization of HIF1α through destabilization of PHD-2 and pVHL. In agreement with these results, targeting of either p38 MAPK, HIF1α, pVHL or PHD-2 effectively mitigated the radiation-induced tube formation of human brain-derived micro-vessel endothelial cells (HB-MEC) and infiltration of glioma cells. Taken together, our findings suggest that targeting HIF1α in combination with ionizing radiation might increase the efficacy of radiotherapy for glioma treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. [Spatiotemporal variations of crop radiation use efficiency and harvest index: research progress].

    Science.gov (United States)

    Li, He-li; Luo, Yi

    2009-12-01

    The radiation use efficiency (RUE) model suggested by Monteith in 1972 is one of the most widely applied approaches for modeling net primary production and crop yield, especially by means of remote sensing techniques. To use this approach, RUE and harvest index (HI) are the two key parameters that need to be defined, besides the absorbed photosynthetically active radiation. However, there exist some problems in the studies and applications of RUE and HI. This paper reviewed the research progress on RUE and HI, summarized the current methods and procedures for defining RUE and HI values when using the RUE approach for predicting crop yield by remote sensing, and proposed that in order to maximize the effective application of RUE and HI in remote sensing crop yield and crop production management, future researches should seek proper procedures to determine the spatial heterogeneities of RUE and HI at regional scale based on field experiments.

  2. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE−/− Alzheimer mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan; Janik, Dirk; Barjaktarovic, Zarko

    2017-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumula...

  3. P2Y2 receptor deficiency aggravates chronic kidney disease progression

    Directory of Open Access Journals (Sweden)

    Sebastian Alexander Potthoff

    2013-09-01

    Full Text Available Purinergic signaling is involved in a variety of physiological states. P2 receptors are mainly activated by adenosine triphosphate (ATP. Activation of specific P2Y receptor subtypes might influence progression of kidney disease. To investigate the in vivo effect of a particular P2 receptor subtype on chronic kidney disease progression, subtotal nephrectomy was performed on wild type (WT and P2Y2 receptor knockout (KO mice.During the observational period of 56 ± 2 days, survival of KO mice was inferior compared to WT mice after SNX. Subtotal nephrectomy reduced creatinine clearance in both groups of mice, but the decrease was significantly more pronounced in KO compared to WT mice (53.9±7.7 vs. 84.3±8.7µl/min at day 56. The KO mice also sustained a greater increase in systolic blood pressure after SNX compared to WT mice (177±2 vs. 156±7 mmHg and a 2.5-fold increase in albuminuria compared to WT. In addition, WT kidneys showed a significant increase in remnant kidney mass 56 days after SNX, but significant attenuation of hypertrophy in KO mice was observed. In line with the observed hypertrophy in WT SNX mice, a significant dose-dependent increase in DNA synthesis, a marker of proliferation, was present in cultured WT glomerular epithelial cells upon ATP stimulation. Markers for tissue damage (TGF-β1, PAI-1 and proinflammatory target genes (MCP1 were significantly upregulated in KO mice after SNX compared to WT SNX mice. In summary, deletion of the P2Y2 receptor leads to greater renal injury after SNX compared to WT mice. Higher systolic blood pressure and inability of compensatory hypertrophy in KO mice are likely causes for the accelerated progression of chronic kidney disease.

  4. PREDICTIVE FACTORS FOR THE PROGRESSION OF CHRONIC CHAGAS CARDIOMYOPATHY IN PATIENTS WITHOUT LEFT VENTRICULAR DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    Silvana de Araújo SILVA

    2015-04-01

    Full Text Available The identification of predictors for the progression of chronic Chagas cardiomyopathy (CCC is essential to ensure adequate patient management. This study looked into a non-concurrent cohort of 165 CCC patients between 1985 and 2010 for independent predictors for CCC progression. The outcomes were worsening of the CCC scores and the onset of left ventricular dysfunction assessed by means of echo-Doppler cardiography. Patients were analyzed for social, demographic, epidemiologic, clinical and workup-related variables. A descriptive analysis was conducted, followed by survival curves based on univariate (Kaplan-Meier and Cox’s univariate model and multivariate (Cox regression model analysis. Patients were followed from two to 20 years (mean: 8.2. Their mean age was 44.8 years (20-77. Comparing both iterations of the study, in the second there was a statistically significant increase in the PR interval and in the QRS duration, despite a reduction in heart rates (Wilcoxon < 0.01. The predictors for CCC progression in the final regression model were male gender (HR = 2.81, Holter monitoring showing pauses equal to or greater than two seconds (HR = 3.02 increased cardiothoracic ratio (HR = 7.87 and time of use of digitalis (HR = 1.41. Patients with multiple predictive factors require stricter follow-up and treatment.

  5. Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice.

    Science.gov (United States)

    Abed, Ahmed; Toubas, Julie; Kavvadas, Panagiotis; Authier, Florence; Cathelin, Dominique; Alfieri, Carlo; Boffa, Jean-Jacques; Dussaule, Jean-Claude; Chatziantoniou, Christos; Chadjichristos, Christos E

    2014-10-01

    Excessive recruitment of monocytes and progression of fibrosis are hallmarks of chronic kidney disease (CKD). Recently we reported that the expression of connexin 43 (Cx43) was upregulated in the kidney during experimental nephropathy. To investigate the role of Cx43 in the progression of CKD, we interbred RenTg mice, a genetic model of hypertension-induced CKD, with Cx43+/- mice. The renal cortex of 5-month-old RenTgCx43+/- mice showed a marked decrease of cell adhesion markers leading to reduced monocyte infiltration and interstitial renal fibrosis compared with their littermates. In addition, functional and histological parameters such as albuminuria and glomerulosclerosis were ameliorated in RenTgCx43+/- mice. Interestingly, treatment with Cx43 antisense produced remarkable improvement of renal function and structure in 1-year-old RenTg mice. Similar results were found in Cx43+/- or wild-type mice treated with Cx43 antisense after obstructive nephropathy. Furthermore, in these mice, Cx43 antisense attenuated E-cadherin downregulation and phosphorylation of the transcription factor Sp1 by the ERK pathway resulting in decreased transcription of type I collagen gene. Interestingly, Cx43-specific blocking peptide inhibited monocyte adhesion in activated endothelium and profibrotic pathways in tubular cells. Cx43 was highly increased in biopsies of patients with CKD. Thus, Cx43 may represent a new therapeutic target against the progression of CKD.

  6. Risk factors for the progression of chronic kidney disease after acute kidney injury.

    Science.gov (United States)

    Pereira, Benedito Jorge; Barreto, Silvana; Gentil, Thais; Assis, Larissa S; Soeiro, Emília Md; Castro, Isac de; Laranja, Sandra M

    2017-08-28

    The incidence of chronic kidney disease (CKD) is increasing with the increasing age of the population and the increasing number of elderly survivors of acute kidney injury (AKI). The risk factors for the progression of CKD after AKI are unclear. To investigate the association between AKI and its progression to CKD and the risk factors involved. An observational, retrospective study of AKI patients followed from 2009 to 2012 was carried out. We evaluated the etiology of AKI, the use of vasoactive drugs and mechanical ventilation, the need for dialysis, the presence of comorbidities, the glomerular filtration rate (GFR), the length of stay and the progression of CKD. Statistical analyses, including the Chi-square test and Pearson's correlation, were performed using SPSS. The 207 patients analyzed had a mean age of 70.1 ± 13.1, and 84.6% of the male patients exhibited decreased renal function and CKD (vs. 60.4% of the female patients). The progression of AKI to CKD was more frequent in patients admitted to wards (63.8%), cancer patients (74.19%), patients with sepsis (67.18%) and patients with obstruction (91.66%). Dialyses were performed in 16.4% of the patients, but this was not correlated with the progression of CKD. Being an elderly male patient with AKI due to sepsis and obstruction was correlated with progression to CKD following discharge. A incidência da doença renal crônica (DRC) está aumentando com o aumento da idade da população e o número crescente de idosos sobreviventes da lesão renal aguda (LRA). Os fatores de risco para a progressão da DRC após a lesão renal aguda (LRA) não são claros. Investigar a associação entre a LRA e sua progressão para a DRC e os fatores de risco envolvidos. Foi realizado estudo observacional, retrospectivo de pacientes com LRA acompanhados de 2009 a 2012. Foram avaliados a etiologia da LRA, o uso de drogas vasoativas, ventilação mecânica, necessidade de diálise, presença de morbidades associadas, ritmo de

  7. Leukemia incidence among people exposed to chronic radiation from the contaminated Techa River, 1953-2005.

    Science.gov (United States)

    Krestinina, Lyudmila; Preston, Dale L; Davis, Faith G; Epifanova, Svetlana; Ostroumova, Evgenia; Ron, Elaine; Akleyev, Alexander

    2010-05-01

    Beginning in 1950, people living on the banks of the Techa River received chronic low-dose-rate internal and external radiation exposures as a result of releases from the Mayak nuclear weapons plutonium production facility in the Southern Urals region of the Russian Federation. The Techa River cohort includes about 30,000 people who resided in riverside villages sometime between 1950 and 1960. Cumulative red bone marrow doses range up to 2 Gy with a mean of 0.3 Gy and a median of 0.2 Gy. Between 1953 and 2005, 93 first primary cases of leukemia, including 23 cases of chronic lymphatic leukemia (CLL), were ascertained among the cohort members. A significant linear dose-response relationship was seen for leukemias other than CLL (P leukemias other than CLL and less than 0 (95% upper bound 1.4) for CLL.

  8. [New markers of progression of chronic heart failure in patients with myocardial infarction, type 2 diabetes and obesity].

    Science.gov (United States)

    Kravchun, P P; Kadykova, O I; Gabisonia, T N

    2015-01-01

    Currently identified a large number of biomarkers that are closely linked with the development of chronic heart failure, some of which are clusterin and fractalkine. Accordingly, the purpose of our study was - to evaluate the role of clusterin and fractalkine in progression of chronic heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. We investigated 71 patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. All patients with postinfarction cardiosclerosis, diabetes and obesity were divided into groups according to the functional class of chronic heart failure (CHF). It was found that an increase the level of fractalkine and reduced clusterin leads due to the development of systolic dysfunction and heart failure progression in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. Fractalkine and clusterin play an important role in progression of the heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity, and this gives them the right to be considered indicators of the severity of CHF.

  9. Longitudinal study of spatially heterogeneous emphysema progression in current smokers with chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Naoya Tanabe

    Full Text Available BACKGROUND: Cigarette smoke is the main risk factor for emphysema, which is a key pathology in chronic obstructive pulmonary disease (COPD. Low attenuation areas (LAA in computed tomography (CT images reflect emphysema, and the cumulative size distribution of LAA clusters follows a power law characterized by the exponent D. This property of LAA clusters can be explained by model simulation, where mechanical force breaks alveolar walls causing local heterogeneous lung tissue destruction. However, a longitudinal CT study has not investigated whether continuous smoking causes the spatially heterogeneous progression of emphysema. METHODS: We measured annual changes in ratios of LAA (LAA%, D and numbers of LAA clusters (LAN in CT images acquired at intervals of ≥ 3 years from 22 current and 31 former smokers with COPD to assess emphysema progression. We constructed model simulations using CT images to morphologically interpret changes in current smokers. RESULTS: D was decreased in current and former smokers, whereas LAA% and LAN were increased only in current smokers. The annual changes in LAA%, D, and LAN were greater in current, than in former smokers (1.03 vs. 0.37%, p=0.008; -0.045 vs. -0.01, p=0.004; 13.9 vs. 1.1, p=0.007, respectively. When LAA% increased in model simulations, the coalescence of neighboring LAA clusters decreased D, but the combination of changes in D and LAN in current smokers could not be explained by the homogeneous emphysema progression model despite cluster coalescence. Conversely, a model in which LAAs heterogeneously increased and LAA clusters merged somewhat in relatively advanced emphysematous regions could reflect actual changes. CONCLUSIONS: Susceptibility to parenchymal destruction induced by continuous smoking is not uniform over the lung, but might be higher in local regions of relatively advanced emphysema. These could result in the spatially heterogeneous progression of emphysema in current smokers.

  10. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  11. Detection of Weak Radiation Involving Generation and Progress of Water Tree

    Science.gov (United States)

    Kumazawa, Takao; Taniguchi, Ryouichi

    It is well known that generation and progress of water tree in XLPE cable are remarkably influenced by inorganic impurities. We have investigated the behavior of them in water tree and reported the experimental results as follows: i) the anomalous increase or decrease in several kinds of inorganic elements was observed in water treed XLPE samples, ii) a distinctive relationship was found for the mass numbers for the elements, iii) the isotopic content of the elements such as Zn deviated over 6% from the natural abundance. These results suggest that water tree is concerned with unknown phenomena e.g., cold fusion or nuclear transmutation in condensed matter. In order to study the relationship between water tree and these phenomena, we attempted to detect neutron, γ-ray or X-ray involving generation and progress of water tree in XLPE samples. For the experiments weak and burst-like radiation seemed to be low energy γ-ray or X-ray was often detected by BF3 and/or CdZnTe counter. The radiation tended to be detected from the samples in which a lot of water trees were generated by supplying inorganic cations abundantly.

  12. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  13. Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Christopher M Blanchette

    2015-04-01

    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. Methods: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000–2/28/2013 and ≥6 months of previous continuous enrollment (baseline within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. Results: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. Conclusions: These results suggest that distribution of patients by age at transition

  14. Effect of chronic microwave radiation on T cell-mediated immunity in the rabbit

    Science.gov (United States)

    Nageswari, K. Sri; Sarma, K. R.; Rajvanshi, V. S.; Sharan, R.; Sharma, Manju; Barathwal, Vinita; Singh, Vinod

    1991-06-01

    Experiments were conducted to elucidate the effects of chronic low power-level microwave radiation on the immunological systems of rabbits. Fourteen male Belgian white rabbits were exposed to microwave radiation at 5 mW/cm2, 2.1 GHz, 3 h daily, 6 days/week for 3 months in two batches of 7 each in specially designed miniature anechoicchambers. Seven rabbits were subjected to sham exposure for identical duration. The microwave energy was provided through S band standard gain horns connected to a 4K3SJ2 Klystron power amplifier. The first batch of animals were assessed for T lymphocyte-mediated cellular immune response mechanisms and the second batch of animals for B lymphocyte-mediated humoral immune response mechanisms. The peripheral blood samples collected monthly during microwave/sham exposure and during follow-up (5/14 days after termination of exposures, in the second batch animals only) were analysed for T lymphocyte numbers and their mitogen responsiveness to ConA and PHA. Significant suppression of T lymphocyte numbers was noted in the microwave group at 2 months ( Prabbits. From these results it is speculated that the T lymphocytes are sequestered to various lymphoid organs under the influence of microwaves. A sub-population of T cells known as T helper cells (mediating DTH response) are probably not affected by microwave radiation. It is clear from our experiments that although chronic microwave radiation at 5 mW/cm2 leads to suppression of peripheral T lymphocyte numbers, there is no concomitant functional impairment of these cells as evidenced by functional assays.

  15. Dynamic clustering of hazard functions: an application to disease progression in chronic heart failure.

    Science.gov (United States)

    Ieva, Francesca; Paganoni, Anna Maria; Pietrabissa, Teresa

    2016-02-04

    We analyse data collected from the administrative datawarehouse of an Italian regional district (Lombardia) concerning patients affected by Chronic Heart Failure. The longitudinal data gathering for each patient hospital readmissions in time, as well as patient-specific covariates, is studied as a realization of non homogeneous Poisson process. Since the aim behind this study is to identify groups of patients behaving similarly in terms of disease progression and then healthcare consumption, we conjectured the time segments between two consecutive hospitalizations to be Weibull distributed in each hidden cluster. Adding a frailty term to take into account the within subjects unknown variability, the corresponding patient-specific hazard functions are reconstructed. Therefore, the comprehensive distribution for each time to event variable is modelled as a Weibull Mixture. We are then able to easily interpret the related hidden groups as healthy, sick, and terminally ill subjects.

  16. [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

    Science.gov (United States)

    Teramoto, Shinji

    2016-05-01

    A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD.

  17. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  18. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model

    DEFF Research Database (Denmark)

    Kempf, S. J.; Janik, Dirk; Barjaktarovic, Zarko

    2016-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer's. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days...... that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer's pathology. It may suggest that ionising radiation functions as a contributing risk factor to this neurodegenerative disease....... with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer's model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates. The radiation-induced changes in the phosphoproteome were associated with the control...

  19. [Living with a chronic progressive form of multiple sclerosis--a balance act].

    Science.gov (United States)

    Hellige, Barbara

    2002-12-01

    There are only a few studies in the German speaking countries available which address the subject of the experience of chronically ill people during the course of their illness. Therefore it was the intent of this present study to find answers for central nurse science issues: How do people who suffer from a chronically progressive course of multiple sclerosis experience the downward trajectory? Which strategies do they develop in order to integrate the disease into their lives? In what ways does the scientific paradigm of medicine influence the perceptions of the illness and the life with it? After an analysis of the national and international state of nursing research follows a description of the methodology of the Grounded Theory and the individual examination steps of the study. The second part examines some essentials of the study. The results show that the trajectory is characterized by four phases. At first the ill person concentrates on the social discussion of the pathogenesis and the medical paradigma. But with physical experiences, exchange with other affected people and acquired information, those concerned develop a very case-specific knowledge. Often disillusioned by the medication strategies, based on the experience that their subjectivity and their individuality are not taken into account, they increasingly disapprove the deficit-oriented perspective of the professionals. They develop distinctly self-caring potentialities. To identify and support this self-care potentialities should be the very core of nursing.

  20. [Effect of paidu baoshen pill in retarding the progression of chronic renal failure].

    Science.gov (United States)

    Wang, Shui-hua; Deng, Hong-tao; Wang, Guo-bin

    2008-08-01

    To assess the impact of Paidu Baoshen Pill (PBP, modified Dahuang Zhechong Pill), in retarding the procession of chronic renal failure (CRF) of stage II-III. The 283 patients of CRF stage II-III were randomly assigned to two groups, 151 patients in the treatment group treated with oral administration of PBP 3 g twice a day, and 132 patients in the control group with oxidative amylase aldehyde enveloped capsule 5-10 capsules thrice a day after meal. The course for both groups was 2 months, and the changes after 1 or 2 courses treatment in scoring of quality of life (QOL) and clinical symptoms, also in laboratory indexes including serum levels of creatinine (Cr), urea nitrogen (UN), and intrinsic creatinine clearance rate were observed. The total effective rate was 70. 86% (107/151 cases) in the treatment group and 44.70% (59/132 cases) in the control group, showing significant difference between them (X2 = 18.69, P < 0.01). Significant differences between groups were also shown in comparisons of scores of QOL and clinical symptoms after treatment. Inter-group comparison showed no difference in all the three indexes detected before treatment, but they did show statistical significance respectively after 1 and 2 courses of treatment (P < 0.05 and P < 0.01). PBP could effectively retard the progression of chronic renal failure and significantly improve the QOL of patients.

  1. Wii Fit balance training or progressive balance training in patients with chronic stroke: a randomised controlled trial

    OpenAIRE

    Yatar, Gozde Iyigun; Yildirim, Sibel Aksu

    2015-01-01

    [Purpose] The aim of this study was to compare the effects of Wii Fit balance training (WBT) and progressive balance training (PBT) approaches on balance functions, balance confidence, and activities of daily living in chronic stroke patients. [Subjects] A total of 30 patients were randomized into the WBT (n=15) and PBT (n=15) groups. [Methods] All of the subjects received exercise training based on a neurodevelopemental approach in addition to either Wii Fit or progressive balance training f...

  2. Aortic Arch Calcification Predicts the Renal Function Progression in Patients with Stage 3 to 5 Chronic Kidney Disease

    OpenAIRE

    Lung-Chih Li; Yueh-Ting Lee; Yi-Wei Lee; Chia-An Chou; Chien-Te Lee

    2015-01-01

    Introduction. The presence of aortic arch calcification (AoAC) and cardiomegaly on chest radiography has been demonstrated as important risk factors for cardiovascular mortality in patients with chronic kidney disease (CKD). However, the interrelationship among AoAC, cardiomegaly, and renal function progression remains unclear. The aim of this study is to assess whether AoAC and cardiomegaly are independently associated with the renal function progression in patients with stages 3–5 CKD. Meth...

  3. Treatment and long-term outcome of chronic radiation esophagitis after radiation therapy for head and neck tumors: A report of 13 cases

    Energy Technology Data Exchange (ETDEWEB)

    Silvain, C.; Barrioz, T.; Besson, I.; Babin, P.; Fontanel, J.P.; Daban, A.; Matuchansky, C.; Beauchant, M. (CHU J Bernard, Poitiers (France))

    1993-05-01

    The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. The authors describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2--120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N = 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding. In conclusion, chronic radiation esophagitis is a severe disease with an underestimated frequency. In this study, peroral dilatations appeared to be necessary and were not associated with an increased morbidity. 21 refs., 1 tab.

  4. Predicting Renal Failure Progression in Chronic Kidney Disease Using Integrated Intelligent Fuzzy Expert System.

    Science.gov (United States)

    Norouzi, Jamshid; Yadollahpour, Ali; Mirbagheri, Seyed Ahmad; Mazdeh, Mitra Mahdavi; Hosseini, Seyed Ahmad

    2016-01-01

    Chronic kidney disease (CKD) is a covert disease. Accurate prediction of CKD progression over time is necessary for reducing its costs and mortality rates. The present study proposes an adaptive neurofuzzy inference system (ANFIS) for predicting the renal failure timeframe of CKD based on real clinical data. This study used 10-year clinical records of newly diagnosed CKD patients. The threshold value of 15 cc/kg/min/1.73 m(2) of glomerular filtration rate (GFR) was used as the marker of renal failure. A Takagi-Sugeno type ANFIS model was used to predict GFR values. Variables of age, sex, weight, underlying diseases, diastolic blood pressure, creatinine, calcium, phosphorus, uric acid, and GFR were initially selected for the predicting model. Weight, diastolic blood pressure, diabetes mellitus as underlying disease, and current GFR(t) showed significant correlation with GFRs and were selected as the inputs of model. The comparisons of the predicted values with the real data showed that the ANFIS model could accurately estimate GFR variations in all sequential periods (Normalized Mean Absolute Error lower than 5%). Despite the high uncertainties of human body and dynamic nature of CKD progression, our model can accurately predict the GFR variations at long future periods.

  5. Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2010-04-01

    Full Text Available Abstract Background Bax inhibitor-1 (BI-1 is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1 to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2 to determine whether HCV and HBV infections modulate said expression. Methods We examined 62 patients: 39 with chronic hepatitis (CH (31 HCV-related and 8 HBV-related; 7 with cirrhosis (6 HCV-related and 1 HBV-related; 13 with hepatocellular carcinoma (HCC [7 in viral cirrhosis (6 HCV- and 1 HBV-related, 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot. Results CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P Conclusions BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.

  6. Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study.

    Directory of Open Access Journals (Sweden)

    Christiane Drechsler

    Full Text Available BACKGROUND: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD. METHODS: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19 using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. RESULTS: Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min, 2.64±1.06 µmol/L (GFR 60-90 ml/min, 2.52±1.24 µmol/L (GFR 30-60 ml/min and 2.05±0.78 µmol/L (GFR<30 ml/min, respectively (p = 0.002. The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005. This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01, and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06. CONCLUSIONS: Homoarginine concentrations are directly correlated with kidney function and are significantly

  7. Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study.

    Science.gov (United States)

    Parsa, Afshin; Kanetsky, Peter A; Xiao, Rui; Gupta, Jayanta; Mitra, Nandita; Limou, Sophie; Xie, Dawei; Xu, Huichun; Anderson, Amanda Hyre; Ojo, Akinlolu; Kusek, John W; Lora, Claudia M; Hamm, L Lee; He, Jiang; Sandholm, Niina; Jeff, Janina; Raj, Dominic E; Böger, Carsten A; Bottinger, Erwin; Salimi, Shabnam; Parekh, Rulan S; Adler, Sharon G; Langefeld, Carl D; Bowden, Donald W; Groop, Per-Henrik; Forsblom, Carol; Freedman, Barry I; Lipkowitz, Michael; Fox, Caroline S; Winkler, Cheryl A; Feldman, Harold I

    2017-03-01

    The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10(-6) for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42×10(-7); replication P=0.039; combined P=7.42×10(-9)). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90×10(-6)). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44×10(-4)) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.

  8. Prospective cohort analyzing risk factors for chronic kidney disease progression in children.

    Science.gov (United States)

    Belangero, Vera M S; Prates, Liliane C; Watanabe, Andreia; Schvartsman, Benita S G; Nussenzveig, Paula; Cruz, Natalia A; Abreu, Ana L S; Paz, Isabel P; Facincani, Inalda; Morgantetti, Fernanda E C; Silva, Andreia O; Andrade, Olberes V B; Camargo, Maria F C; Nogueira, Paulo C Koch

    2017-10-02

    To identify risk factors for chronic kidney disease (CKD) progression in Brazilian children and to evaluate the interactions between factors. This was a multicenter prospective cohort in São Paulo, involving 209 children with CKD stages 3-4. The study outcome included: (a) death, (b) start of kidney replacement therapy, (c) eGFR decrease >50% during the followup. Thirteen risk factors were tested using univariate regression models, followed by multivariable Cox regression models. The terms of interaction between the variables showing significant association with the outcome were then introduced to the model. After a median follow-up of 2.5 years (IQR=1.4-3.0), the outcome occurred in 44 cases (21%): 22 started dialysis, 12 had >50% eGFR decrease, seven underwent transplantation, and three died. Advanced CKD stage at onset (HR=2.16, CI=1.14-4.09), nephrotic proteinuria (HR=2.89, CI=1.49-5.62), age (HR=1.10, CI=1.01-1.17), systolic blood pressure Z score (HR=1.36, CI=1.08-1.70), and anemia (HR=2.60, CI=1.41-4.77) were associated with the outcome. An interaction between anemia and nephrotic proteinuria at V1 (HR=0.25, CI=0.06-1.00) was detected. As the first CKD cohort in the southern hemisphere, this study supports the main factors reported in developed countries with regards to CKD progression, affirming the potential role of treatments to slow CKD evolution. The detected interaction suggests that anemia may be more deleterious for CKD progression in patients without proteinuria and should be further studied. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. The clinical and laboratory characteristics of acute spontaneous urticaria and its progression to chronic spontaneous urticaria.

    Science.gov (United States)

    Magen, Eli; Zueva, Ekaterina; Mishal, Joseph; Schlesinger, Menachem

    2016-09-01

    The natural history of the progression from acute spontaneous urticaria (ASU) to chronic spontaneous urticaria (CSU), CSU remains poorly understood. To identify clinical and laboratory patient attributes that may be predictive of ASU progression to CSU. We prospectively studied consecutive adult patients (age ≥ 18 years) with a diagnosis of urticaria of urticaria activity score assessment were performed in all the patients at baseline and then at weeks 7, 12, 24, and 48. Of 114 patients with acute urticaria and without identifiable causes, 73 patients (64%) were included in the ASU group, 41 patients in the CSU group (36%), and 44 healthy subjects in the control group. At baseline, 26 patients in the CSU group (63.4%) had a positive ASST result, whereas only 17 patients with a positive ASST result (23.3%) were revealed in the ASU group (p < 0.001). Patients with baseline ASST positive results were characterized by more profound basopenia (mean [standard deviation], 0.05 ± 0.08 cell/mm(3)) and more anti-thyroid peroxidase antibodies (18 [41.8%]) than those with the negative baseline ASST result (mean [standard deviation], 0.13 ± 0.09 cell/mm(3), p < 0.001 more profound basopenia; and 13 (18.1%), p = 0.009 more thyroid peroxidase antibodies). We observed the disappearance of ASST positive result in some patients with CSU with baseline positive ASST results, whereas, in some subjects with CSU, baseline negative ASST results came to be positive results throughout the study period. A baseline positive ASST result of patients with ASU was a significant determinant (odds ratio 5.91 [95% confidence interval, 2.57-13.62]; p < 0.001) for a CSU diagnosis at week 7. The patients with ASU who progressed toward CSU were characterized by a positive ASST result, thyroid autoimmunity, and profound basopenia at baseline.

  10. Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Geng; Wei Zheng; Cong-Mei Wu; Shu-Qiang Wang; Quan Hong; Guang-Yan Cai; Xiang-Mei Chen

    2016-01-01

    Background: Chronic kidney disease (CKD) has become a public health problem.New interventions to slow or prevent disease progression are urgently needed.In this setting, cell therapies associated with regenerative effects are attracting increasing interest.We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD.Methods: Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy.We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogets (GMs) on the 5/6 nephrectomized kidney.The viability of ESCs within the GMs was detected using in vio two-photon fluorescence confocal imaging.Rats were sacrificed after 12 weeks.Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results.Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining.Results: In vitro, ESCs could be automatically loaded into the GMs.Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro.After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs.Conclusions: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.

  11. Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia.

    Directory of Open Access Journals (Sweden)

    Cynthia Yu-Wai-Man

    Full Text Available Chronic progressive external ophthalmoplegia (CPEO is a classical mitochondrial ocular disorder characterised by bilateral progressive ptosis and ophthalmoplegia. These ocular features can develop either in isolation or in association with other prominent neurological deficits (CPEO+. Molecularly, CPEO can be classified into two distinct genetic subgroups depending on whether patients harbour single, large-scale mitochondrial DNA (mtDNA deletions or multiple mtDNA deletions secondary to a nuclear mutation disrupting mtDNA replication or repair. The aim of this magnetic resonance imaging (MRI study was to investigate whether the ophthalmoplegia in CPEO is primarily myopathic in origin or whether there is evidence of contributory supranuclear pathway dysfunction.Ten age-matched normal controls and twenty patients with CPEO were recruited nine patients with single, large-scale mtDNA deletions and eleven patients with multiple mtDNA deletions secondary to mutations in POLG, PEO1, OPA1, and RRM2B. All subjects underwent a standardised brain and orbital MRI protocol, together with proton magnetic resonance spectroscopy in two voxels located within the parietal white matter and the brainstem.There was evidence of significant extraocular muscle atrophy in patients with single or multiple mtDNA deletions compared with controls. There was no significant difference in metabolite concentrations between the patient and control groups in both the parietal white matter and brainstem voxels. Volumetric brain measurements revealed marked cortical and cerebellar atrophy among patients with CPEO+ phenotypes.The results of this study support a primary myopathic aetiology for the progressive limitation of eye movements that develops in CPEO.

  12. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation.

    Science.gov (United States)

    Rybkina, Valentina L; Azizova, Tamara V; Scherthan, Harry; Meineke, Viktor; Doerr, Harald; Adamova, Galina V; Teplyakova, Olga V; Osovets, Sergey V; Bannikova, Maria V; Zurochka, Alexander V

    2014-11-01

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  13. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rybkina, Valentina L.; Azizova, Tamara V.; Adamova, Galina V.; Teplyakova, Olga V.; Osovets, Sergey V.; Bannikova, Maria V. [Southern Urals Biophysics Institute, Ozyorsk, Chelyabinsk Region (Russian Federation); Scherthan, Harry; Meineke, Viktor; Doerr, Harald [University of Ulm, Bundeswehr Institute of Radiobiology, Munich (Germany); Zurochka, Alexander V. [Immunology Institute, Yekaterinburg (Russian Federation)

    2014-11-15

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  14. Pro-A-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the MMKD Study.

    Science.gov (United States)

    Dieplinger, Benjamin; Mueller, Thomas; Kollerits, Barbara; Struck, Joachim; Ritz, Eberhard; von Eckardstein, Arnold; Haltmayer, Meinhard; Kronenberg, Florian

    2009-02-01

    A-type natriuretic peptide (ANP) and adrenomedullin (ADM) are potent hypotensive, diuretic, and natriuretic peptides involved in maintaining cardiovascular and renal homeostasis. We conducted a prospective 7-year study of 177 nondiabetic patients with primary chronic kidney disease to see if ANP and ADM plasma concentrations predict the progression of their disease, using novel sandwich immunoassays covering the midregional epitopes of the stable prohormones (MRproANP and MR-proADM). Progression of chronic kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure, which occurred in 65 patients. Analysis of the receiver operating characteristic curve for the prediction of renal endpoints showed similar areas under the curve for the glomerular filtration rate (GFR) (0.838), MR-proANP (0.810), and MRproADM (0.876), respectively, as did the Kaplan-Meier curve analyses of the patients stratified according to the median of the respective markers. In separate multiple Cox-proportional hazard regression analyses, increased plasma concentrations of both peptides were each strongly predictive of the progression of chronic kidney disease after adjustments for age, gender, GFR, proteinuria and amino-terminal pro-B-type natriuretic peptide. Our study suggests that MR-proANP and MR-proADM are useful new markers of progression of primary nondiabetic chronic kidney disease.

  15. Progress Towards A Dedicated Synchrotron Radiation Source For Ultrafast X-Ray Science

    Science.gov (United States)

    Lidia, Steve

    2002-03-01

    We present progress towards the design of a femtosecond synchrotron radiation x-ray source based on a flat-beam rf gun and a recirculating superconducting linac that provides beam to an array of undulators and bend magnets. Optical pulse durations of <100 fs are obtained by a combination of electron pulse compression, transverse temporal correlation of the electrons, and x-ray pulse compression. After an introduction and initial scientific motivation, we cover the following aspects of the design: layout and lattice, ultra-fast x-ray pulse production, flat electron-beam production, the rf gun, rf systems, cryogenic systems, collective effects, photon production, and synchronization of x-ray and laser pulses. We conclude with a summary of issues and areas of development that remain to be addressed.

  16. Effects of noinionizing radiation on the central nervous system, behavior, and blood: a progress report.

    Science.gov (United States)

    McRee, D I; Elder, J A; Gage, M I; Reiter, L W; Rosenstein, L S; Shore, M L; Galloway, W D; Adey, W R; Guy, A W

    1979-01-01

    This paper presents a progress report on the U. S. research which has been designated as collaborative research with the Soviet Union to study the biological effects of nonionizing radiation on the central nervous system, behavior, and blood. Results of investigations to study the effects of microwaves on isolated nerves, synaptic function, transmission of neural impulses, electroencephalographic recordings, behavior, and on chemical, cytochemical and immunological properties of the blood are presented. Specifically, the effects of microwave exposure on chick brain and cat spinal cords, on EEG patterns of rats, on behavioral of neonatal rats exposed during development, on behavior of adult rats, on behavior of rhesus monkeys and on the pathology, hematology, and immunology of rabbits will be reported in a summary format. Much of the information is new and has not been published previously. PMID:446443

  17. Progress In Iron Transmission Measurements Relevant to the Solar Convection/Radiation Boundary

    Science.gov (United States)

    Bailey, Jim; Nagayama, T.; Loisel, G.; Rochau, G. A; Blancard, C.; Colgan, J.; Cosse, Ph; Faussurier, G.; Fontes, Christopher J; Golovkin, I.; Hansen, S. B; Iglesias, C. A; Kilcrease, D. P; MacFarlane, Joseph J.; Mancini, Roberto; Nahar, S. N; Nash, T. J; Orban, Chris; Pinsonneault, Marc H.; Pradhan, Anil Kumar; Sherrill, M.; Wilson, B. G

    2014-06-01

    Iron plasma opacity influences the internal structure of the sun. However, opacity models have never been experimentally tested at stellar interior conditions. Recent iron opacity experiments at the Sandia Z facility reached 195 eV temperatures, nearly the same as the solar convection/radiation zone boundary (CZB), at electron densities that are roughly ½ the solar CZB value. Progress to solidify these results and use them to examine the physical underpinnings of opacity models will be described. We will also discuss impact of the results on the Rosseland mean opacities important for stellar physics.++Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under contract DE-AC04-94AL85000.

  18. Progress in Z-Pinch driven dynamic-hohlraums for high-temperature radiation-flow and ICF experiments at Sandia National Laboratories.

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, James E.; Haines, Malcolm G. (Imperial College, London, United Kingdom); Chandler, Gordon Andrew; Bliss, David Emery; Olson, Richard Edward; Sanford, Thomas W. L.; Olson, Craig Lee; Nash, Thomas J.; Ruiz, Carlos L.; Matzen, Maurice Keith; Idzorek, George C. (Los Alamos National Laboratory, Los Alamos, NM); Stygar, William A.; Apruzese, John P. (Naval Research Laboratory, Washington DC); Cuneo, Michael Edward; Cooper, Gary Wayne (University of New Mexico, Albuquerque, NM); Chittenden, Jeremy Paul (Imperial College, London, United Kingdom); Chrien, Robert E. (Los Alamos National Laboratory, Los Alamos, NM); Slutz, Stephen A.; Mock, Raymond Cecil; Leeper, Ramon Joe; Sarkisov, Gennady Sergeevich (Ktech Corporation, Albuquerque, NM); Peterson, Darrell L. (Los Alamos National Laboratory, Los Alamos, NM); Lemke, Raymond William; Mehlhorn, Thomas Alan; Roderick, Norman Frederick (University of New Mexico, Albuquerque, NM); Watt, Robert G. (Los Alamos National Laboratory, Los Alamos, New MM)

    2004-06-01

    Progress in understanding the physics of dynamic-hohlraums is reviewed for a system capable of generating 13 TW of axial radiation for high temperature (>200 eV) radiation-flow experiments and ICF capsule implosions.

  19. Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Eun Joo; Kim, Dong Hun; Yoon, Seong Ho [Chosun University College of Medicine, Gwangju (Korea, Republic of); Suk, Eun Ha [Dept. of Anaesthesiology and Pain Medicine, Seonam University College of Medicine, Namwon (Korea, Republic of)

    2013-06-15

    Metastatic pulmonary calcification (MPC) is common in patients with chronic renal failure. The authors experienced a patient with chronic renal failure and primary hyperparathyroidism by parathyroid adenoma accompanied with rapid progressions of MPC and alveolar hemorrhage. Recent chest radiographs, compared with previous chest radiographs, showed rapid accumulation of calcification in both upper lungs. Following up on the high-resolution CT scan after five years demonstrates more increased nodules in size and ground glass opacity. The patient was diagnosed with MPC and alveolar hemorrhage by transbronchial lung biopsy. We assumed rapid progression of MPC and alveolar hemorrhage in underlying chronic renal failures could be a primary hyperparathyroidism which may be caused by parathyroid adenoma detected incidentally. Therefore parathyroid adenoma was treated with ethanol injections. Herein, we have reported on CT findings of MPC with alveolar hemorrhage and reviewed our case along with other articles.

  20. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

    DEFF Research Database (Denmark)

    Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L

    1995-01-01

    Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml.min-1.1.73 m-2 (11-43) (median, range) and 15 sex, age, and body mass index matched....../I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...... control subjects with normal renal function were studied. Fasting blood glucose was comparable and in the non-diabetic range in the two groups as was the oral glucose tolerance test. Patients demonstrated hyperinsulinaemia both during fasting (p

  1. Radiation Promotes Colorectal Cancer Initiation and Progression by Inducing Senescence-Associated Inflammatory Responses

    Science.gov (United States)

    Kim, Sang Bum; Bozeman, Ronald; Kaisani, Aadil; Kim, Wanil; Zhang, Lu; Richardson, James A.; Wright, Woodring E.; Shay, Jerry W.

    2015-01-01

    Proton radiotherapy is becoming more common since protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared to conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIR) which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence associated gene (P19Arf) are markedly increased. Following these changes loss of Casein kinase Iα (CKIα) and induction of chronic DNA damage and TP53 mutations are increased compared to x-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, CDDO-EA, reduces proton irradiation associated SIR and tumorigenesis. Thus, exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA. PMID:26477319

  2. The effectiveness of electromagnetic terahertz radiation use in the treatment of patients with rapidly progressive periodontitis

    Directory of Open Access Journals (Sweden)

    Zelenova A.V.

    2015-12-01

    Full Text Available The aim: to increase the efficiency of treatment of patients with rapidly progressive periodontitis (RPP using electromagnetic radiation at terahertz frequencies of molecular spectrum of radiation and absorption of nitric oxide 150,176-150,664 GHz. Material and methods. The study involved 50 patients with RPP, which according to the method of therapy were divided into 2 groups: group 1 included patients receiving conventional therapy, group 2 consisted of patients who, along with traditional therapy received EHF-therapy device "Orbit" YAKUL.941526.001. The control group consisted of 20 healthy subjects with intact periodontium. For the non-invasive study of tissue blood flow in the periodontal tissue Doppler ultrasound was used MiniMax-Doppler-Phono. The study of the microvasculature of periodontitis has been conducted. To determine the reactivity of microvascular periodontal tissue reflex functional tests on the indirect effect of the cold were performed. Results. Reductions achieved values of periodontal indices, especially important index PMA, a significant increase in the linear blood flow indices, decreased pulse pressure gradient and the index followed appropriate reduction to their cold test. Conclusion. The proposed complex therapy can accelerate the relief of inflammation in the periodontal tissues of the complex, to improve the elastic properties of blood vessels, reduce their tone and restore microcirculation in periodontal tissues.

  3. Dysregulation of apoptosis: a possible mechanism leading to chronic progressive renal histological changes in lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To evakuate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes. Methods Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN),12 patientswith lgA nephropathy lgAN, 4 patients with idiopathic easangnioproliferative lomerulonephritis(MsPGN) and 3 patients with acute poststreptococcal gornerulonephritis (APGN).Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults wes used as control. Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patiants. Results Compared to other proliferative glomerulonephritis and controls, the patients with lupus nephritis had lase apoptotic cells, a higher ratio of PCNA+cells/TdT+cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r=0.4983 (P=0.0132), r -0.8399 (P<0.001), r=0.6614 (,P=0.0033),respactively. P/T retios in the glomerulus and tubule had a positive correlation with 24-hour urinary protein,r=0.8554(P<0.001) and r=0.7134 (P=0.001); and a negative correlation with crsetinine clearance (Ccr), r=-0.4880(P=0.0133) and r=-0.7229(P=0.001),which in tubules positively correlated with serum creatinine (Scr), r=0.4107 (P=0.0414). Conclusions Apoptosis is reduced in proliferative lupus nephritis. Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renalhistopathological changes.

  4. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    Science.gov (United States)

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). Conclusions Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID:27275467

  5. Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis

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    Srivastava S

    2008-01-01

    Full Text Available Purpose: Ethambutol (EMB is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. Methods: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. Results: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02. Massive infiltration and exacerbated lung pathology with increased expression of IFN-γ and TNF-α was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-α resulting in increased lung pathology. Conclusion: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.

  6. Progressive glomerulosclerosis and renal failure following perinatal gamma radiation in the beagle

    Energy Technology Data Exchange (ETDEWEB)

    Jaenke, R.S.; Phemister, R.D.; Norrdin, R.W.

    1980-06-01

    The renal effects of whole body irradiation in the perinatal period were studied in the dog. Ninety-three dogs received a single sublethal exposure in the range of 270 to 435 R in either late gestation (55 days postcoitus) or early postnatal life (2 days postpartum) and were sacrificed at 70 days, 2, or 4 years of age. Early renal lesions in 70-day-old irradiated dogs were characterized by arrested glomerular maturation and degeneration resulting in reduced functional renal mass. Mature glomeruli exhibited mesangial proliferation. At 2 and 4 years of age, surviving irradiated dogs exhibited sever renal disease associated with progressive glomerular damage which was characterized by mesangial proliferation and compression of capillary lumina, epithelial degeneration and focal capsular adhesions, and ultimately obliterative glomerulosclerosis. Twenty-one of the 93 irradiated dogs died in renal failure before 4 years of age with advanced glomerulosclerosis. The phatogenesis of this progressive renal lesion may be related to the interaction of three specific factors. These include (1) the effect of direct radiation damage to mature kidney components; (2) the loss of outer cortical nephrons resulting in increased work load of the surviving nephrons; and (3) the effect of compensatory hypertrophy related to the loss of renal parenchyma as the rapid growth rates associated with kidney maturation.

  7. Retarding chronic kidney disease (CKD progression: a practical nutritional approach for non-dialysis CKD

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    Vincenzo Bellizzi

    2016-10-01

    Full Text Available This is a case report on a patient with non-dialysis chronic kidney disease (CKD in whom several nutritional issues are briefly discussed from a practical point of view. The article is accompanied by an editorial published in this Journal in relation to the 2nd International Conference of the European Renal Nutrition working group at ERA-EDTA—“Retarding CKD progression: readily available through comprehensive nutritional management?”—and focuses on several practical topics associated with the nutritional approach for the conservative treatment of non-dialysis CKD. The article is divided into 3 sections—basic nutritional assessment, nutritional targets, and nutritional follow-up in non-dialysis CKD—linked to 3 consecutive steps of the clinical follow-up of the patient and the related nutritional concerns and intervention. First visit: Baseline nutritional assessment and basic nutritional considerations in non-dialysis chronic kidney disease (CKD • What nutritional assessment/monitoring for protein-energy wasting (PEW should be employed? • Is a body mass index (BMI of 21 kg/m2 adequate? • What phosphate target should be pursued? • What are the nutritional habits in patients with incident CKD? • What protein needs and amount of dietary protein should be pursued? • Does the quality of protein matter? • What amount of dietary salt should be employed? How should this be obtained? • How should normal serum phosphate be achieved? • What diet should be recommended? Is a vegetarian diet an option? Second visit: Major nutritional targets in non-dialysis CKD • Consequences of unintentional weight loss • What is the role of the renal dietitian in helping the patient adhere to a renal diet? Intermediate visits: Nutritional follow-up in non-dialysis CKD • What treatment for calcium/parathyroid hormone (PTH will affect CKD progression? Final visits: • Would a dietary recall/intensive dietary education improve adherence with

  8. Radiation biophysicl study of biological molecules. Progress report, February 1, 1975--June 30, 1976. [Fast electrons, gamma and uv radiation, Escherichia coli, T1 and lambda bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Fluke, D.J.

    1976-01-01

    Progress is reported on the following research projects: direct action target investigation of molecular weights of enzymes exposed to fast electrons; direct action gamma radiation dosimetry with T/sub 1/ bacteriophage; uv radiation sensitivity of T/sub 1/ bacteriophage on various host strains of E. coli; temperature dependence of uv radiation direct action on dry T/sub 1/ bacteriophage; investigation of light and temperature effects during incubation of T/sub 1/ bacteriophage exposed to fast electrons; test of superoxide anion as a radiation intermediate in cellular radiobiology; uv action spectra related to error-prone repair; uv-reactivation experiments with T/sub 1/ and lambda bacteriophages; and split-dose uv mutagenesis in E. coli. (HLW)

  9. Recent progress in thermodynamics of radiation——exergy of radiation, effective temperature of photon and entropy constant of photon

    Institute of Scientific and Technical Information of China (English)

    CHEN ZeShao; MO SongPing; HU Peng

    2008-01-01

    The recent progress on thermodynamic properties of spectral radiant energy in the field of thermodynamics of radiation is reviewed. The effective temperature of photon Tλ representing the energy quality of photon is introduced. The relation tropy constant of photon is given as sλ=3.72680×10-23 J/K. The exergy, entropy and enthalpy of the spectral blackbody radiation, the equilibrium cavity radiation, the radiation flux in open system are discussed by using Tλ and sλ, as well as the en-tropy change in the process of the state transformation of photon gas. By analyzing the exergy of spectral radiation, the exergy efficiency of spectral radiant energy available for photosynthesis is proved to be higher than that of light energy. The method for the irreversible loss of exergy calculation in radiant energy converters is also discussed.

  10. Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

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    Sadanori Akita

    2010-01-01

    Full Text Available Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

  11. Progress With Developing Use of Gene Editing To Cure Chronic Infection With Hepatitis B Virus.

    Science.gov (United States)

    Ely, Abdullah; Moyo, Buhle; Arbuthnot, Patrick

    2016-04-01

    Chronic infection with hepatitis B virus (HBV) occurs in approximately 6% of the world's population. Carriers of the virus are at risk for life-threatening complications, and developing curative treatment remains a priority. The main shortcoming of licensed therapies is that they do not affect viral covalently closed circular DNA (cccDNA), a stable intermediate of replication. Harnessing gene editing to mutate cccDNA provides the means to inactivate HBV gene expression permanently. Reports have described use of engineered zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) nucleases. Although inhibition of viral replication has been demonstrated, reliably detecting mutations in cccDNA has been difficult. Also, the dearth of murine models that mimic cccDNA formation has hampered analysis in vivo. To reach a stage of clinical use, efficient delivery of the editors to HBV-infected hepatocytes and limiting unintended off-target effects will be important. Investigating therapeutic efficacy in combination with other treatment strategies, such as immunotherapies, may be useful to augment antiviral effects. Advancing gene editing as a mode of treating HBV infection is now at an interesting stage and significant progress is likely to be made in the immediate future.

  12. Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies

    Energy Technology Data Exchange (ETDEWEB)

    Alcindor, F. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Valderrama, R. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Canavaggio, M. (Abbott Labs., North Chicago, IL (United States)); Lee, H. (Abbott Labs., North Chicago, IL (United States)); Katz, A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Montesinos, C. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Madrid, R.E. (New York State Office of Mental Retardation and Developmental Disabilities, Inst. for Basic Research in Developmental Disabilities, NY (United States)); Merino, R.R. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Pipia, P.A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States))

    1992-12-01

    We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 mem and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific. (orig.)

  13. Chronic progressive external ophthalmoplegia: II. A qualitative and quantitative electronmicroscopy study of skeletal muscles

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    Elza Dias-Tosta

    1988-06-01

    Full Text Available This study quantifies the maior electron microscopic changes in limb muscle biopsies from 31 out of 34 patients with the syndrome of chronic progressive external ophthalmoplegia. Patients were divided into three clinical groups - A 10 sporadic cases with muscle weakness only; B 9 familial cases with muscle weakness only; C 15 cases with muscle weakness and one or more of the following features: pigmentary retinopathy, cerebellar ataxia, pyramidal signs and peripheral neuropathy. Electron microscopic mitochondrial abnormalities were found in all groups (8 patients from group A, 3 from group B, 14 from group C. Quantitative measurements of certain muscle fibre constituents, using a point-counting technique, revealed decreased myofibril volume-fractions and increased volume-fractions of mitochondria, glycogen and lipid in some biopsies from each group. Mitochondrial volume-fractions correlated positively with lipid content, the proportion of type 1 fibres, and the percentage of fibres with increased oxidative enzyme activity. The three groups defined clinically showed no significant differences in terms of the relative proportions of these measured constituents.

  14. Transgenerational accumulation of radiation damage in small mammals chronically exposed to Chernobyl fallout.

    Science.gov (United States)

    Ryabokon, Nadezhda I; Goncharova, R I

    2006-09-01

    The purpose of this investigation has been the analysis of the long-term development of biological damage in natural populations of a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber), which were chronically exposed to low doses of ionizing radiation over 22 animal generations within 10 years following the Chernobyl accident. The time course of the biological end-points (chromosome aberrations in bone marrow cells and embryonic lethality) was compared with the time course of the whole-body absorbed dose rate from external and internal exposure in the studied populations inhabiting monitoring sites in Belarus with different ground deposition of radionuclides. The yield of chromosome aberrations and, in lesser degree, embryonic lethality was associated with the radionuclide contamination of the monitoring areas in a dose-dependent manner. As a main feature of the long-term development of biological damage under low dose rate irradiation, permanently elevated levels of chromosome aberrations and an increasing frequency of embryonic lethality have developed over 22 animal generations. This contrasts with the assumption that the biological damage would gradually disappear since in the same period of time the whole-body absorbed dose rate decreased exponentially with a half-value time of about 2.5-3 years. Furthermore, gravid females were captured, and their offspring, born and grown up under contamination-free laboratory conditions, showed the same enhanced level of chromosome aberrations. Therefore the authors suggest that, along with the biological damage attributable to the individual exposure of each animal, the observed cellular and systemic effects reflect the transgenerational transmission and accumulation, via genetic and/or epigenetic pathways, of damage attributable to the chronic low-dose rate exposure of the preceding generations of animals. They also suggest that the level of the accumulated transmissible damage in the investigated

  15. EFFECT OF CHRONIC RADIATION ON PLANT-PATHOGEN INTERACTIONS IN 30-KM CHERNOBYL ZONE

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    Dmitriev A.

    2012-08-01

    Full Text Available It was established in pot experiments that infection with powdery mildew (Erysiphe graminis DC. f. sp. tritici Em. Marchal and brown rust (Puccinia triticana Erikss. & Henn. of three wheat (Triticum aestivum L. cultivars ('Mironovskaya 808', 'Polesskay 70', and 'Kiyanka' grown from seeds, collected in the Chernobyl exclusion zone, was 1.5–2.0 times higher than that of plants grown from control seeds. On filed plots in the Chernobyl zone, wheat plant resistance to biotic stress was reduced. At artificial infection with brown rusts, the disease development was enhanced on plots with increased radiation background. One of the mechanisms of declined phytoimmunity potential under the action of low doses of chronic irradiation is evidently a reduced activity of plant proteinase inhibitors. Thus, in wheat and rye (Secale cereale L., cv. ‘Saratovskaya’ kernels, their activity reduced by 35–60% as compared to control. Active form and race formation in the population of the grass stem rust causal agent (Puccinia graminis Pers. was observed in the Chernobyl zone. A “new” population of this fungus with high frequency of more virulent clones than in other Ukraine regions was distinguished. The results obtained independently in greenhouse and field trials performed in the Chernobyl zone demonstrated radiation stress influence on the pathogen–plant system. They indicate a necessity of monitoring the microevolutionary processes occurring in both plants and their pathogens under conditions of technogenic stresses.

  16. Magnetic resonance imaging may simulate progressive multifocal leucoencephalopathy in a patient with chronic lymphocytic leukemia after fludarabine therapy

    Directory of Open Access Journals (Sweden)

    Kalita J

    2008-01-01

    Full Text Available A 60-year-old male with chronic lymphatic leukemia (CLL after 6 months of fludarabine therapy was admitted with status epilepticus and developed left hemiplegia. His magnetic resonance imaging revealed multiple T2 hyperintense lesions in the right frontal and left parieto-occipital lesion, simulating progressive multifocal leucoencephalopathy (PML. Cerebrospinal fluid Polymerase Chain Reaction (PCR for JC virus was negative. We suggest the possible role of fludarabine in producing PML-like lesions in patients with Chronic Lymphocytic Leukemia (CLL.

  17. Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. [Paramecium tetraurelia; Synechococcus lividus

    Energy Technology Data Exchange (ETDEWEB)

    Planel, H.; Soleilhavoup, J.P.; Tixador, R.; Richoilley, G.; Conter, A.; Croute, F.; Caratero, C.; Gaubin, Y.

    1987-05-01

    Investigations carried out on the protozoan Paramecium tetraurelia and the cyanobacteria Synechococcus lividus, which were shielded against background radiation or exposed to very low doses of gamma radiation, demonstrated that radiation can stimulate the proliferation of these two single-cell organisms. Radiation hormesis depends on internal factors (age of starting cells) and external factors (lighting conditions). The stimulatory effect occurred only in a limited range of doses and disappeared for dose rates higher than 50 mGy/y.

  18. [Radiation situation prognosis for deep space: reactions of water and living systems to chronic low-dose ionizing irradiation].

    Science.gov (United States)

    Ushakov, I B; Tsetlin, V V; Moisa, S S

    2013-01-01

    The authors review the findings of researches into the effects of low-dose ionizing irradiation on diverse biological objects (embryonic Japanese quails, Aspergillus niger, Spirostomum ambiguum Ehrbg., mesenchymal stem cells from mouse marrow, dry higher plants seeds, blood lymphocytes from pilots and cosmonauts). Model experiments with chronic exposure to ionizing radiation doses comparable with the measurements inside orbital vehicles and estimations for trips through the interplanetary space resulted in morphological disorders (embryonic Japanese quails, Aspergillus niger), radiation hormesis (Aspergillus niger, MSCs from mouse marrow), increase in the seed germination rate, inhibition of Spirostomum spontaneous activity, DNA damages, chromosomal aberrations, and increase of the blood lymphocytes reactivity to additional radiation loading. These facts give grounds to assume that the crucial factor in the radiation outcomes is changes in liquid medium. In other words, during extended orbiting within the magnetosphere region and interplanetary missions ionizing radiation affects primarily liquids of organism and, secondarily, its morphofunctional structures.

  19. The effects of chronic radiation on reproductive success of the polychaete worm Neanthes arenaceodentata

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, F.L.; Anderson, S.L.

    1988-12-01

    The effects of lifetime exposure to chronic irradiation on reproductive success were assessed for laboratory populations of the polychaete worm Neanthes arenaceodentata. Lifetime exposure was initiated upon the spawning of the P1 female and was terminated upon spawning of the F1 female. Groups of experimental worms received either no radiation (controls) or 0.19, 2.1, or 17 mGy/h. The total dose received by the worms was either background or approximately 0.55, 6.5, or 54 Gy, respectively. The broods from the F1 mated pairs were sacrificed before hatching occurred, and information was obtained on brood size, on the number of normal and abnormal embryos, and on the number of embryos that were living, dying, and dead. The mean number of embryos in the broods from the F1 females exposed to lifetime radiation of 0.19 and 2.1 mGy/h was not significantly different from the mean number of embryos from control females; however, the mean number of embryos was different from those F1 females exposed to 17 mGy/h. There was a significant reduction in the number of live embryos in the broods from the F1 mated pairs that were exposed to the lowest dose rate given, 0.19 mGy/h, as well as those exposed to 2.1 and 17 mGy/h. Also, increased percentages of abnormal embryos were determined in the broods of all the radiation-exposed groups. 39 refs., 10 figs., 15 tabs.

  20. Response of shortgrass Plains vegetation to chronic and seasonally administered gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fraley, Jr., Leslie [Colorado State Univ., Fort Collins, CO (United States)

    1971-08-01

    In order to determine the effect of radiation on the structure of native shortgrass plains vegetation, an 8750 Ci 137Cs source was installed on the Central Plains Experimental Range near Nunn, Colorado; The experimental area was divided into 6 treatment sectors, a control, 2 sectors for chronic exposure (irradiation initiated April 1969 and continuing as of August 1971), and one each for spring, summer and late fall seasonal semi-acute (30 day), exposures which were administered during April, July and December, 1969, respectively. Community structure was measured by coefficient of community and diversity index. Yield was determined by clipping plots in September 1970 and visual estimates in September 1969 and 1970 for the grass-sedge component of the vegetation. Individual species sensitivity was determined by density data recorded in April, June and September of 1969 and 1970 and by a phenological index recorded at weekly intervals during the 1969 and 1970 growing seasons. The response of the vegetation was similar whether determined by coefficient of community or diversity with diversity being a more sensitive measure of effects. In the chronically exposed sectors, the exposure rate which resulted in a 50 per cent reduction in these 2 parameters (CC50 or D50) was still decreasing the second growing season and was approximately 18 R/hr for the CC50 as of June 1970 and 10 R/hr for the D50 as of September 1970. For the seasonally exposed sectors, the late fall period (December, 1969) was the most sensitive, summer (July, 1969) the least sensitive and spring (April, 1969) intermediate with CC50 and D50 values of 195 and 90, 240 and 222, and 120 and 74 R/hr for the spring, summer and late fall exposed sectors, respectively. Yield and density data indicated a rapid revegetation of the spring and summer exposed sectors during 1970 as a result of an influx of invader species such as Salsola kali tenuifolia, Chenopodium leptophyllum and Lepidium densiflorum and the

  1. HIV-1 subtype C envelope characteristics associated with divergent rates of chronic disease progression

    Directory of Open Access Journals (Sweden)

    Goulder Philip JR

    2010-11-01

    is an important correlate of disease progression in chronic HIV-1 subtype C infection.

  2. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Directory of Open Access Journals (Sweden)

    Katrina Vanura

    Full Text Available Chronic lymphocytic leukemia (CLL is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200. CMV-DNA was detected in 3% (6/200 of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03 and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001. Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06 and mean decay values differed significantly from those of total IgG (p=0.034. Boosts of CMV-specific antibody levels were observed in 49% (22/45 of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively. VZV-specific IgG even became undetectable in 18% (9/50 of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered

  3. Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy.

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    Jingjing Zhou

    Full Text Available BACKGROUND: Uromodulin, or Tamm-Horsfall protein, is the most abundant urinary protein in healthy individuals. Recent studies have suggested that uromodulin may play a role in chronic kidney diseases. We examined an IgA nephropathy cohort to determine whether uromodulin plays a role in the progression of IgA nephropathy. METHODS: A total of 344 IgA nephropathy patients were involved in this study. Morphological changes were evaluated with the Oxford classification of IgA nephropathy. Enzyme Linked Immunosorbent Assay (ELISA measured the urinary uromodulin level on the renal biopsy day. Follow up was done regularly on 185 patients. Time-average blood pressure, time-average proteinuria, estimated glomerular filtration rate (eGFR and eGFR decline rate were caculated. Association between the urinary uromodulin level and the eGFR decline rate was analyzed with SPSS 13.0. RESULTS: We found that lower baseline urinary uromodulin levels (P = 0.03 and higher time-average proteinuria (P = 0.04 were risk factors for rapid eGFR decline in a follow-up subgroup of the IgA nephropathy cohort. Urinary uromodulin level was correlated with tubulointerstitial lesions (P = 0.016. Patients that had more tubular atrophy/interstitial fibrosis on the surface had lower urinary uromodulin levels (P = 0.02. CONCLUSIONS: Urinary uromodulin level is associated with interstitial fibrosis/tubular atrophy and contributes to eGFR decline in IgA nephropathy.

  4. Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.

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    Maria Göbel

    Full Text Available Progranulin (Pgrn is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN, is significantly higher expressed in aggressive CD38(+ZAP-70(+ as compared to indolent CD38(-ZAP-70(- chronic lymphocytic leukemia (CLL cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p- as detected by flourescence in situ hybridization (FISH and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163. Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13-3.76, p = 0.018, unmutated IGHV status (HR = 5.63, 95%-CI = 3.05-10.38, p<0.001, high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09-3.89, p = 0.026 but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA.

  5. Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

    Science.gov (United States)

    Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

    2016-08-01

    Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This

  6. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

    OpenAIRE

    Keirstead Hans S; Nistor Gabriel; Radojicic Milan

    2007-01-01

    Abstract Background Chronic spinal cord injury (SCI) can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an In...

  7. Risk prediction for chronic kidney disease progression using heterogeneous electronic health record data and time series analysis

    OpenAIRE

    Perotte, Adler; Ranganath, Rajesh; Hirsch, Jamie S; Blei, David; Elhadad, Noémie

    2015-01-01

    Background As adoption of electronic health records continues to increase, there is an opportunity to incorporate clinical documentation as well as laboratory values and demographics into risk prediction modeling. Objective The authors develop a risk prediction model for chronic kidney disease (CKD) progression from stage III to stage IV that includes longitudinal data and features drawn from clinical documentation. Methods The study cohort consisted of 2908 primary-care clinic patients who h...

  8. Telomere Length in Aged Mayak PA Nuclear Workers Chronically Exposed to Internal Alpha and External Gamma Radiation.

    Science.gov (United States)

    Scherthan, Harry; Sotnik, Natalia; Peper, Michel; Schrock, Gerrit; Azizova, Tamara; Abend, Michael

    2016-06-01

    Telomeres consist of GC-rich DNA repeats and the "shelterin" protein complex that together protect chromosome ends from fusion and degradation. Telomeres shorten with age due to incomplete end replication and upon exposure to environmental and intrinsic stressors. Exposure to ionizing radiation is known to modulate telomere length. However, the response of telomere length in humans chronically exposed to radiation is poorly understood. Here, we studied relative telomere length (RTL) by IQ-FISH to leukocyte nuclei in a group of 100 workers from the plutonium production facility at the Mayak Production Association (PA) who were chronically exposed to alpha-emitting ((239)Pu) radiation and/or gamma (photon) radiation, and 51 local residents serving as controls, with a similar mean age of about 80 years. We applied generalized linear statistical models adjusted for age at biosampling and the second exposure type on a linear scale and observed an age-dependent telomere length reduction. In those individuals with the lowest exposure, a significant reduction of about 20% RTL was observed, both for external gamma radiation (≤1 Gy) and internal alpha radiation (≤0.05-0.1 Gy to the red bone marrow). In highly exposed individuals (>0.1 Gy alpha, 1-1.5 Gy gamma), the RTL was similar to control. Stratification by gender revealed a significant (∼30%) telomere reduction in low-dose-exposed males, which was absent in females. While the gender differences in RTL may reflect different working conditions, lifestyle and/or telomere biology, absence of a dose response in the highly exposed individuals may reflect selection against cells with short telomeres or induction of telomere-protective effects. Our observations suggest that chronic systemic exposure to radiation leads to variable dose-dependent effects on telomere length.

  9. High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Kanda Eiichiro

    2013-01-01

    Full Text Available Abstract Background Metabolic acidosis leads to chronic kidney disease (CKD progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD, 70.4 (6.6 years; eGFR, 25.7 (13.6 ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2 mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8 mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3 mEq/l]: adjusted hazard ratio (HR, 3.511 (95% CI, 1.342-9.186. A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI, 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

  10. Radiation physics, biophysics and radiation biology. Progress report for October 1, 1979-September 30, 1980. [Lead abstract

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, H.H.; Hall, E.J.

    1980-07-01

    Separate abstracts were prepared for 31 of the 32 papers presented in this progress report. The other paper is represented by an abstract only and deals with field shaping and recalibration of x-ray facilities.

  11. Progress on Clinical Study of Acupuncture Treatment for Chronic Pelvic Inflammation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wen-jie; HUANG Guo-qi

    2008-01-01

    @@ Chronic pelvic inflammation is mostly caused byincomplete treatment of acute pelvic inflammation orby transference from pathologic condition due to poorbody constitution, including chronic endometritis,chronic salpingo-oophoritis and chronic inflammationof connective tissue, and is a commonly andfrequently encountered disease in the gynecologydepartment. Due to long duration, intractablecondition and high recurrent rate, it is also acommonly encountered reason to induce heterotopicpregnancy, sterility, pelvic pain and pelvic adhesivediseases. In the investigative study on the domesticliterature about acupuncture treatment of chronicpelvic inflammation in the recent five years, theauthor hopes to summarize the information forreference in the clinical treatment and to point outsome issues existing in the current clinical study.

  12. Different Phenotyping Approaches Lead to Dissimilar Biologic Profiles in Men With Chronic Fatigue After Radiation Therapy.

    Science.gov (United States)

    Feng, Li Rebekah; Dickinson, Kristin; Kline, Neila; Saligan, Leorey N

    2016-12-01

    Cancer-related fatigue (CRF) persists months after treatment completion. Although a CRF biomarker has not yet been identified, validated self-report questionnaires are used to define and phenotype CRF in the discovery of potential biomarkers. The purposes of this study are to identify CRF subjects using three well-known CRF phenotyping approaches using validated self-report questionnaires and to compare the biologic profiles that are associated with each CRF phenotype. Fatigue in men with nonmetastatic prostate cancer receiving external beam radiation therapy was measured at baseline (T1), midpoint (T2), end point (T3), and one-year post-external beam radiation therapy (T4) using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and Patient Reported Outcomes Measurement Information System-Fatigue. Chronic fatigue (CF) and nonfatigue subjects were grouped based on three commonly used phenotyping approaches: 1) T4 FACT-F 50. Differential gene expressions using whole-genome microarray analysis were compared in each of the phenotyping criterion. The study enrolled 43 men, where 34%-38% had CF based on the three phenotyping approaches. Distinct gene expression patterns were observed between CF and nonfatigue subjects in each of the three CRF phenotyping approaches: 1) Approach 1 had the largest number of differentially expressed genes and 2) Approaches 2 and 3 had 40 and 21 differentially expressed genes between the fatigue groups, respectively. The variation in genetic profiles for CRF suggests that phenotypic profiling for CRF should be carefully considered because it directly influences biomarker discovery investigations. Published by Elsevier Inc.

  13. Effects of chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes.

    Science.gov (United States)

    Katsube, Takanori; Wang, Bing; Tanaka, Kaoru; Ninomiya, Yasuharu; Varès, Guillaume; Kawagoshi, Taiki; Shiomi, Naoko; Kubota, Yoshihisa; Liu, Qiang; Morita, Akinori; Nakajima, Tetsuo; Nenoi, Mitsuru

    2017-01-01

    Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53(+/-)) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53(+/+)) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53(+/+) C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.

  14. NRC TLD Direct Radiation Monitoring Network. Progress report, July--September 1993: Volume 13, No. 3

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1993-11-01

    This report provides the status and results of the NRC Thermoluminescent Dosimeter (TLD) Direct Radiation Monitoring Network. It presents the radiation levels measured in the vicinity of NRC licensed facilities throughout the country for the third quarter of 1993.

  15. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S. [Russian Inst. of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2000-05-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant <> for processing and temporary storage

  16. Ionizing radiation exposures in treatments of solid neoplasms are not associated with subsequent increased risks of chronic lymphocytic leukemia.

    Science.gov (United States)

    Radivoyevitch, Tomas; Sachs, Rainer K; Gale, Robert Peter; Smith, Mitchell R; Hill, Brian T

    2016-04-01

    Exposure to ionizing radiation is not thought to cause chronic lymphocytic leukemia (CLL). Challenging this notion are recent data suggesting CLL incidence may be increased by radiation exposure from the atomic bombs (after many decades), uranium mining and nuclear power facility accidents. To assess the effects of therapeutic ionizing radiation for the treatment of solid neoplasms we studied CLL risks in data from the Surveillance, Epidemiology, and End Results (SEER) Program. Specifically, we compared the risks of developing CLL in persons with a 1(st) non-hematologic cancer treated with or without ionizing radiation. We controlled for early detection effects on CLL risk induced by surveillance after 1(st) cancer diagnoses by forming all-time cumulative CLL relative risks (RR). We estimate such CLL RR to be 1.20 (95% confidence interval, 1.17, 1.23) for persons whose 1(st) cancer was not treated with ionizing radiation and 1.00 (0.96, 1.05) for persons whose 1(st) cancer was treated with ionizing radiations. These results imply that diagnosis of a solid neoplasm is associated with an increased risk of developing CLL only in persons whose 1(st) cancer was not treated with radiation therapy.

  17. NRC TLD direct radiation monitoring network: Progress report, July--September 1997. Volume 17, Number 3

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1998-01-01

    The US Nuclear Regulatory Commission (NRC) Direct Radiation Monitoring Network is operated by the NRC in cooperation with participating states to provide continuous measurement of the ambient radiation levels around licensed NRC facilities, primarily power reactors. Ambient radiation levels result from naturally occurring radionuclides present in the soil, cosmic radiation constantly bombarding the earth from outer space, and the contribution, if any, from the monitored facilities and other man-made sources. The Network is intended to measure radiation levels during routine facility operations and to establish background radiation levels used to assess the radiological impact of an unusual condition, such as an accident. This report presents the radiation levels measured around all facilities in the Network for the third quarter of 1996. A complete listing of the site facilities monitored is included. In some instances, two power reactor facilities are monitored by the same set of dosimeters (e.g., Kewaunee and Point Beach).

  18. Effects of chronic exposure to ionising radiation in the Pacific oyster Crassostrea gigas

    Energy Technology Data Exchange (ETDEWEB)

    Fievet, B.; Devos, A.; Voiseux, C.; Leconte-Pradines, C. [Institut de Radioprotection et de Surete' Nucleaire (France); Dallas, L.; Jha, A. [University of Plymouth (United Kingdom)

    2014-07-01

    The Cotentin peninsula (Normandy, France) hosts nuclear industry facilities which operate with controlled discharges of radionuclides in the marine environment. Compared to natural radioactivity, the increase by artificial radionuclides is small but constant. As a consequence, marine species are chronically exposed to low additional doses of ionizing radiation (IR). The effects of chronic exposure to radionuclides were investigated in early stages of development of the Japanese oyster Crassostrea gigas. On the basis of literature, mollusks are expected to be particularly resistant to acute IR (UNSCEAR, 1996. Sources and effects of ionizing radiation. Report to the General Assembly, with Scientific Annex. 86 p). Two different chronic exposure conditions consisted in external ({sup 137}Cs) and internal ({sup 241}Am) irradiation for two weeks. Biological endpoints were analyzed in parallel at both the integrated (growth) and molecular (target stress gene expression) levels. To identify potential biological targets of IR, oysters were first exposed to very high dose rates and radionuclide activities with the perspective to reduce the levels and to derive dose-response curves. Although the initial exposure levels ({sup 137}Cs 30 000 μGy.h{sup -1}; {sup 241}Am 57 000 Bq.L{sup -1}) were many orders of magnitude higher than those encountered in the natural environment, no significant change in the measured parameters was observed. This result was surprising because data from the literature showed that exposure of mussel Mytilus edulis to {sup 3}H at lower doses rates (10-100 μGy.h{sup -1}) induced DNA damage in hemocytes (Jha et al., 2005. Impact of low doses of tritium on the marine mussel, Mytilus edulis: Genotoxic effects and tissue-specific bioconcentration. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 586, 47-57). To understand this apparent discrepancy between those two filtering bivalves, a new experiment was performed to compare the response

  19. Radiation safety protocol for high dose 131I therapy of thyroid carcinoma in patients on hemodialysis for chronic renal failure.

    Science.gov (United States)

    Modarresifar, Homayoun; Almodovar, Samuel; Bass, William B; Ojha, Buddhiwardhan

    2007-02-01

    Iodine ablation therapy for thyroid cancer on patients receiving dialysis poses unique radiation safety challenges. Exposure to gamma and beta negative particles by the hemodialysis (HD) staff is a concern that has not been well studied. A 53-y-old male patient on HD for chronic renal failure was scheduled for 131I high dose therapy as treatment for thyroid papillary carcinoma. The patient was on HD every other day, prior to ablation. A high dose of 131I (3,607.5 MBq) was required. The patient was admitted for 131I therapy, and continued HD. Thyroid cancer ablation therapy was administered according to our institutional protocol. New radiation safety measures were developed and implemented in order to give the patient an optimal treatment dose, reduce radiation to the patient (critical organs and whole body), and to protect the HD personnel. This included placing two lead shields between the patient and the HD nurse, and HD monitoring by two alternating nurses to reduce their radiation exposure. Film badges were used to measure radiation exposure to the nursing staff. Dosimetry calculations were obtained to determine radiation absorbed doses by the optic lens, skin, and whole body. Quality control verification for this shielding arrangement proved to be effective in protecting the HD staff against gamma and beta negative radiation from recent 131I high dose therapy. Implementation of this model proved to be an effective and adequate radiation safety protocol for limiting radiation exposure to the HD staff. The patient was given 3607.5 MBq for optimal treatment after HD. Hemodialysis was repeated after approximately 48 and 96 h to remove excess 131I and reduce radiation to the patient.

  20. Association of relative telomere length with progression of chronic kidney disease in two cohorts: effect modification by smoking and diabetes.

    Science.gov (United States)

    Raschenberger, Julia; Kollerits, Barbara; Ritchie, James; Lane, Beverley; Kalra, Philip A; Ritz, Eberhard; Kronenberg, Florian

    2015-07-07

    Chronic kidney disease (CKD) is a highly progressive disease. We studied the association between relative telomere length (RTL) and CKD progression and tested whether this association is modified by smoking and diabetes mellitus. RTL was measured by qPCR in two prospective cohort studies, the MMKD-Study (n = 166) and the CRISIS-Study (n = 889) with a median follow-up of 4.5 and 2.8 years, respectively. Progression was defined as doubling of baseline serum creatinine (MMKD-Study) and/or end stage renal disease (both studies). 59 and 105 of the patients from MMKD and CRISIS experienced a progression of CKD. Mean standardized pooled RTL was 0.74 ± 0.29. In the meta-analysis shorter RTL at baseline showed a borderline association with CKD progression (HR = 1.07 [95%CI 1.00-1.15]; p = 0.06). We observed an effect modification of RTL and CKD progression by smoking and diabetes (p-values of interaction p = 0.02 and p = 0.09, respectively). Each 0.1 unit shorter RTL was significantly associated with an increased hazard for CKD progression in active-smokers by 44% (HR = 1.44 [1.16-1.81]; p = 0.001) and in patients with diabetes mellitus by 16% (HR = 1.16 [1.01-1.34]; p = 0.03). Estimates were adjusted for baseline age, sex, proteinuria and GFR. This study in two independent cohorts reinforces that RTL is a marker and potentially a pathogenetic factor for CKD progression.

  1. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Faezeh Ghasemi

    2016-07-01

    Full Text Available Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus(HBV is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  2. Acoustic radiation force on a sphere in a progressive and standing zero-order quasi-Bessel-Gauss beam.

    Science.gov (United States)

    Jiang, Chen; Liu, Xiaozhou; Liu, Jiehui; Mao, Yiwei; Marston, Philip L

    2017-04-01

    By means of series expansion theory, the incident quasi-Bessel-Gauss beam is expanded using spherical harmonic functions, and the beam coefficients of the quasi-Bessel-Gauss beam are calculated. According to the theory, the acoustic radiation force function, which is the radiation force per unit energy on a unit cross-sectional surface on a sphere made of diverse materials and immersed in an ideal fluid along the propagation axis of zero-order quasi-Bessel-Gauss progressive and standing beams, is investigated. The acoustic radiation force function is calculated as a function of the spherical radius parameter ka and the half-cone angle β with different beam widths in a progressive and standing zero-order Bessel-Gauss beam. Simulation results indicate that the acoustic radiation forces with different waist radii demonstrate remarkably different features from those found in previous studies. The results are expected to be useful in potential applications such as acoustic tweezers. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Optical coherence tomography and autofluorescence findings in chronic phototoxic maculopathy secondary to snow-reflected solar radiation

    Directory of Open Access Journals (Sweden)

    Dhananjay Shukla

    2015-01-01

    Full Text Available A professional mountain trekker presented with gradual, moderate visual decline in one eye. The subnormal vision could not be explained by the examination of anterior and posterior segment of either eye, which was unremarkable. Optical coherence tomography and autofluorescence imaging revealed subtle defects in the outer retina, which correlated with the extent of visual disturbance. A novel presentation of retinal phototoxicity due to indirect solar radiation reflected from snow in inadequately protected eyes of a chronically exposed subject is reported.

  4. Progress and Status on the Development of NASA's Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) model

    Science.gov (United States)

    Mertens, C. J.; Tobiska, W. K.; Blattnig, S. R.; Kress, B. T.; Wiltberger, M. J.; Solomon, S. C.; Kunches, J.; Murray, J. J.

    2008-12-01

    The NASA Applied Sciences Program recently selected a project for funding through the Research Opportunities in Space and Earth Sciences (ROSES) solicitation. The project objective is to develop a nowcast prediction of air-crew radiation exposure from both background galactic cosmic rays (GCR) and solar energetic particle events (SEP) that may accompany solar storms. The new air-crew radiation exposure model is called the Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) model. NAIRAS will provide global, data-driven, real-time radiation dose predictions of biologically harmful radiation at commercial airline altitudes. Observations are utilized from the ground (neutron monitors), from the atmosphere (the NCEP reanalysis), and from space (NASA/ACE and NOAA/GOES). Atmospheric observations provide the overhead shielding information and the ground- and space-based observations provide boundary conditions on the incident GCR and SEP particle flux distributions for transport and dosimetry simulations. Dose rates are calculated using the parametric AIR (Atmospheric Ionizing Radiation) model and the physics-based HZETRN (High Charge and Energy Transport) code. In this paper we discuss the concept and design of the NAIRAS model, and present recent progress in the implementation and give examples of the model results. Specifically, we show predictions of representative annual background exposure levels and radiation exposure levels for selected SEP events during solar cycle 23, with emphasis on the high-latitude and polar region. We also characterize the suppression of the geomagnetic cutoff rigidity during these storm periods and their subsequent influence on atmospheric radiation exposure. We discuss the key uncertainties and areas that need improvement in both model and data, the timeline for project completion, and access to model results.

  5. Effects of proactive population-based nephrologist oversight on progression of chronic kidney disease: a retrospective control analysis

    Directory of Open Access Journals (Sweden)

    Lee Brian

    2012-08-01

    Full Text Available Abstract Background Benefits of early nephrology care are well-established, but as many as 40% of U.S. patients with end-stage renal disease (ESRD do not see a nephrologist before its onset. Our objective was to evaluate the effect of proactive, population-based nephrologist oversight (PPNO on chronic kidney disease (CKD progression. Methods Retrospective control analysis of Kaiser Permanente Hawaii members with CKD using propensity score matching methods. We matched 2,938 control and case pairs of individuals with stage 3a CKD for the pre-PPNO period (2001–2004 and post-PPNO period (2005–2008 that were similar in other characteristics: age, gender, and the presence of diabetes and hypertension. After three years, we classified the stage outcomes for all individuals. We assessed the PPNO effect across all stages of progression with a χ2- test. We used the z-score test to assess the proportional differences in progression within a stage. Results The progression within the post-PPNO period was less severe and significantly different from the pre-PPNO period (p = 0.027. Within the stages, there were 2.6% more individuals remaining in 3a in the post-period (95% confidence interval [CI], 1.5% to 3.8%; P value P value = 0.0017, 3a to 4/5 was 0.2% less (95% CI, 0.0% to 0.87%; P value = 0.26, and 3a to ESRD was 0.24% less (95% CI, 0.0% to 0.66%, P value = 0.10. Conclusions Proactive, population-based nephrologist oversight was associated with a statistically significant decrease in progression. With enabling health information technology, risk stratification and targeted intervention by collaborative primary and specialty care achieves population-level care improvements. This model may be applicable to other chronic conditions.

  6. Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis

    NARCIS (Netherlands)

    C.J. van der Woude (Janneke); H. Moshage; M. Homan; J.H. Kleibeuker (Jan); P.L.M. Jansen (Peter); H. van Dekken (Herman)

    2005-01-01

    textabstractBACKGROUND: Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)-carcinoma sequence. AIMS: To investigate the expression of apoptosis and inflammatory related proteins in CUC. METHO

  7. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation.

    Science.gov (United States)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak

    2015-10-01

    A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50mGy adapting dose administered acutely (0.40Gy/min) or chronically (1.4mGy/h or 4.1mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100mGy and 1Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50mGy at 1.4mGy/h followed by 1Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100mGy), no differences at the level of mutation were found comparing different dose rates. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Foro, Palmira, E-mail: pforo@parcdesalutmar.cat [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Algara, Manuel [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Lozano, Joan [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Rodriguez, Nuria; Sanz, Xavier [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Torres, Erica [Pathology Department, Parc de Salut Mar, Barcelona (Spain); Carles, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Department of Oncology, Hospital Vall d' Hebron, Barcelona (Spain); Reig, Anna; Membrive, Ismael [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Quera, Jaume [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Fernandez-Velilla, Enric; Pera, Oscar [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Lacruz, Marti [Universitat Pompeu Fabra, Barcelona (Spain); Radiation Protection Department, Parc de Salut Mar, Barcelona (Spain); Bellosillo, Beatriz [Universitat Pompeu Fabra, Barcelona (Spain); Pathology Department, Parc de Salut Mar, Barcelona (Spain)

    2014-04-01

    Purpose: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. Methods and Materials: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. Results: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). Conclusions: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of

  9. [Anthropometric evaluation of pediatric patients with non-progressive chronic encephalopathy according to different methods of classification].

    Science.gov (United States)

    Teixeira, Jéssica Socas; Gomes, Mirian Martins

    2014-09-01

    To perform anthropometric assessment of patients with quadriplegic, chronic non-progressive encephalopathy, comparing two distinct references of nutritional classification, and to compare the estimated height to the length measured by stadiometer. Cross-sectional study including 0-3-year children with quadriplegic, chronic non-progressive encephalopathy in secondary public hospital. Length, weight, arm circumference, triceps skinfold and knee height were measured. The arm muscle circumference and estimated height were calculated. The following relations were evaluated: weight-for-age, length-for-age and weight-for-length, using as reference the charts of the the World Health Organization (WHO) and those proposed by Krick et al. Fourteen children with a mean age of 21 months were evaluated. Assessment of anthropometric indicators showed significant difference between the two classification methods to assess nutritional indicators length/age (p=0.014), weight/age (p=0.014) and weight/length (p=0.001). There was significant correlation between measured length and estimated height (r=0.796, p=0.001). Evaluation of arm circumference and triceps skinfold showed that most patients presented some degree of malnutrition. According to arm muscle circumference, most were eutrophic. Specific curves for children with chronic non-progressive encephalopathy appear to underestimate malnutrition when one takes into account indicators involving weight. Curves developed for healthy children can be a good option for clinical practice and weight-for-length indicator and body composition measurements should be considered as complementary tools. Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Keirstead Hans S

    2007-09-01

    Full Text Available Abstract Background Chronic spinal cord injury (SCI can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4, 28 (n = 4, 120 (n = 4, 450 (n = 5, or 540 (n = 5 days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures. Results Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil. Conclusion Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of

  11. Recent progress in thermodynamics of radiation——exergy of radiation, effective temperature of photon and entropy constant of photon

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The recent progress on thermodynamic properties of spectral radiant energy in the field of thermodynamics of radiation is reviewed. The effective temperature of photon Tλ representing the energy quality of photon is introduced. The relation between Tλ and the wavelength λ is given as λTλ =c3=5.33016×10?3 m·K. The en- tropy constant of photon is given as sλ=3.72680×10?23 J/K. The exergy, entropy and enthalpy of the spectral blackbody radiation, the equilibrium cavity radiation, the radiation flux in open system are discussed by using Tλ and sλ, as well as the en- tropy change in the process of the state transformation of photon gas. By analyzing the exergy of spectral radiation, the exergy efficiency of spectral radiant energy available for photosynthesis is proved to be higher than that of light energy. The method for the irreversible loss of exergy calculation in radiant energy converters is also discussed.

  12. Can we delay the progression of chronic kidney disease (CKD) by improving collaboration between renal units and primary care teams?

    Science.gov (United States)

    Thomas, N

    2005-01-01

    This paper will discuss why nephrology teams should collaborate with primary care teams in delaying the progression of chronic kidney disease (CKD), and explain how they can collaborate to improve the outcomes for patients who eventually need dialysis. The paper will describe the staging of CKD and will discuss evidence-based guidelines for the management of CKD in the community. Practical examples of how a specialist renal nurse can improve communication with primary care and can improve the outcome of patients with early kidney disease will be described.

  13. Progress on an Updated National Solar Radiation Data Base for the United States: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, S.; Anderberg, M.; George, R.; Marion, W.; Myers, D.; Renne, D.; Beckman, W.; DeGaetano, A.; Gueymard, C.; Perez, R.; Plantico, M.; Stackhouse, P.; Vignola, F.

    2005-09-01

    In 1992, The National Renewable Energy Laboratory (NREL) released the 1961-1990 National Solar Radiation Data Base (NSRDB), a 30-year set of hourly solar radiation data. In 2003, NREL undertook an NSRDB update project for the decade of 1991-2000.

  14. Progress on an Updated National Solar Radiation Data Base for the United States

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, S.; Anderberg, M.; George, R.; Marion, W.; Myers, D.; Renne, D.; Beckman, W.; DeGaetano, A.; Gueymard, C.; Perez, R.; Plantico, M.; Stackhouse, P.; Vignola, F.

    2005-01-01

    In 1992, the National Renewable Energy Laboratory (NREL) released the 1961-1990 National Solar Radiation Data Base (NSRDB), a 30-year set of hourly solar radiation data. In 2003, NREL undertook an NSRDB update project for the decade of 1991-2000. This paper describes recent work on the project and evaluation of the test data set.

  15. NRC TLD Direct Radiation Monitoring Network. Progress report, October--December 1996

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1997-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1996. It provides the ambient radiation levels measured in the vicinity of 74 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program. 3 figs., 4 tabs.

  16. NRC TLD Direct Radiation Monitoring Network progress report, October--December 1994. Volume 14, No. 4

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1995-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1994. It provides the ambient radiation levels measured in the vicinity of 75 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program.

  17. Basal values and changes of liver stiffness predict the risk of disease progression in compensated advanced chronic liver disease.

    Science.gov (United States)

    Pons, Mònica; Simón-Talero, Macarena; Millán, Laura; Ventura-Cots, Meritxell; Santos, Begoña; Augustin, Salvador; Genescà, Joan

    2016-10-01

    Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD). Ninety-four patients with baseline LSM ≥10kPa, Child-Pugh score 5 and without previous decompensation were included. A second LSM was performed during follow-up and data on liver function and liver-related events were collected. The primary endpoint was a composite that included death, liver decompensation and impairment in at least 1 point in Child-Pugh score. After a median follow-up of 43.6 months, 15% of patients presented the primary endpoint. Multivariate analysis identified baseline LSM (OR 1.12, P=0.002) and delta-LSM (OR 1.02, P=0.048) as independent predictors of the primary endpoint. A high risk group represented by patients with baseline LSM ≥21kPa and delta-LSM ≥10% (risk of progression 47.1%, 95% CI: 23-71%) was identified, while patients with LSM <21kPa and delta-LSM <10% presented zero risk of progression (P=0.03). Simple classification rules using baseline LSM and delta-LSM identify cACLD patients at low or high risk of disease progression. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  18. Thioredoxin-1 protects against neutrophilic inflammation and emphysema progression in a mouse model of chronic obstructive pulmonary disease exacerbation.

    Directory of Open Access Journals (Sweden)

    Naoya Tanabe

    Full Text Available BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms. RESULTS: Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1, and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1. CONCLUSION: Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms

  19. NREL Solar Radiation Resource Assessment Project: Status and outlook. FY 1991 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Renne, D.; Riordan, C.; Maxwell, E.; Stoffel, T.; Marion, B.; Rymes, M.; Wilcox, S.; Myers, D.

    1992-05-01

    This report summarizes the activities and accomplishments of NREL`s Solar Radiation Resource Assessment Project during fiscal year 1991. Currently, the primary focus of the SRRAP is to produce a 1961--1990 National Solar Radiation Data Base, providing hourly values of global horizontal, diffuse, and direct normal solar radiation at approximately 250 sites around the United States. Because these solar radiation quantities have been measured intermittently at only about 50 of these sites, models were developed and applied to the majority of the stations to provide estimates of these parameters. Although approximately 93% of the data base consists of modeled data this represents a significant improvement over the SOLMET/ERSATZ 1952--1975 data base. The magnitude and importance of this activity are such that the majority of SRRAP human and financial in many other activities, which are reported here. These include the continued maintenance of a solar radiation monitoring network in the southeast United States at six Historically Black Colleges and Universities (HBCU`s), the transfer of solar radiation resource assessment technology through a variety of activities, participation in international programs, and the maintenance and operation of NREL`s Solar Radiation Research Laboratory. 17 refs.

  20. A randomized controlled trial of gabapentin for chronic low back pain with and without a radiating component

    Science.gov (United States)

    Atkinson, J. Hampton; Slater, Mark A.; Capparelli, Edmund V.; Patel, Shetal M.; Wolfson, Tanya; Gamst, Anthony; Abramson, Ian S.; Wallace, Mark S.; Funk, Stephen D.; Rutledge, Thomas R.; Wetherell, Julie Loebach; Matthews, Scott C.; Zisook, Sidney; Garfin, Steven R.

    2016-01-01

    Gabapentin is prescribed for analgesia in chronic low back pain, yet there are no controlled trials supporting this practice. This randomized, two-arm, 12-week, parallel group study compared gabapentin (forced titration up to 3600 mg daily) to inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment measured by the Descriptor Differential Scale; the secondary outcome was disability (Oswestry Disability Index). The intention-to-treat analysis comprised 108 randomized chronic back pain patients (daily pain for ≥ 6 months) whose pain did (43%) or did not radiate into the lower extremity. Random effects regression models which did not impute missing scores were used to analyze outcome data. Pain intensity decreased significantly over time (p < .0001) with subjects on gabapentin or placebo reporting reductions of about 30% from baseline, but did not differ significantly between groups (p = .423). The same results pertained for disability scores. In responder analyses of those who completed 12 weeks (N=72), the proportion reporting at least 30% or 50% reduction in pain intensity, or at least “Minimal Improvement” on the Physician Clinical Global Impression of Change did not differ significantly between groups. There were no significant differences in analgesia between participants with radiating (n = 46) and non-radiating (n = 62) pain either within or between treatment arms. There was no significant correlation between gabapentin plasma concentration and pain intensity. Gabapentin appears to be ineffective for analgesia in chronic low back pain with or without a radiating component. PMID:26963844

  1. Dyspnoea assessed by visual analogue scale in patients with chronic obstructive lung disease during progressive and high intensity exercise.

    Science.gov (United States)

    Noseda, A; Carpiaux, J P; Schmerber, J; Yernault, J C

    1992-01-01

    BACKGROUND: A study was carried out to determine whether rating of dyspnoea by means of a visual analogue scale during a progressive exercise test is affected by the subject's awareness of the progressive nature of the protocol. METHODS: Nineteen patients with chronic obstructive lung disease (FEV1 mean (SE) 1.06 (0.07) 1) were studied. A preliminary incremental test was carried out with a work rate increasing by 10 watts every minute until the subject could no longer exercise, to determine the maximum work load (Wmax) and to anchor the upper end of the visual analogue scale. This was followed by two exercise tests performed one day apart in randomised sequence, with two different protocols. One was a 12 minute protocol that included two sudden bursts of three minute high intensity exercise, up to the subject's Wmax, each preceded by three minutes of low level exercise. The other test was a conventional three minute incremental test lasting 12 minutes. On both study days the only information given to the subject about the temporal profile of load was that a change would be made every three minutes. The relation between dyspnoea, as assessed by the visual analogue scale, and ventilation, measured during high intensity or progressive exercise, was studied. RESULTS: The mean (SE) rates of increase of dyspnoea with increasing ventilation (% of line length 1(-1) min) obtained by linear regression analysis were similar for the two tests (2.86 (0.20) for progressive exercise and 2.87 (0.25) for high intensity exercise); it was 2.59 (0.25) for the initial burst of high intensity exercise when the data on this were analysed separately. In six subjects with stable disease studied again two months later the reproducibility of the rating of dyspnoea was reasonably good for both protocols. CONCLUSION: The results suggest that in most patients with chronic obstructive lung disease the assessment of exercise induced dyspnoea by means of a visual analogue scale during a

  2. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.

    2016-01-01

    Background & Aims: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. Methods: We performed a cross-sectional study of 669 patients with a first episode of acute pancre

  3. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ali, U.A.; Issa, Y.; Hagenaars, J.C.; Bakker, O.J.; Goor, H. van; Nieuwenhuijs, V.B.; Bollen, T.L.; Ramshorst, B. van; Witteman, B.J.; Brink, M.A.; Schaapherder, A.F.; Dejong, C.H.; Spanier, B.W.; Heisterkamp, J.; Harst, E. van der; Eijck, C.H. van; Besselink, M.G.; Gooszen, H.G.; Santvoort, H.C. van; Boermeester, M.A.

    2016-01-01

    BACKGROUND & AIMS: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. METHODS: We performed a cross-sectional study of 669 patients with a first episode of acute

  4. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.|info:eu-repo/dai/nl/380766086; Bakker, Olaf J.|info:eu-repo/dai/nl/314099050; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.|info:eu-repo/dai/nl/304821721; Boermeester, Marja A.

    2016-01-01

    Background & Aims: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. Methods: We performed a cross-sectional study of 669 patients with a first episode of acute

  5. Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Cook John A

    2010-02-01

    Full Text Available Abstract Background The histamine receptor-1 (H1-antagonist, loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma (HT29. Methods Cells were treated with several doses of loratadine at several time points before and after exposure to radiation. Radiation dose modifying factors (DMF were determined using full radiation dose response survival curves. Cell cycle phase was determined by flow cytometry and the expression of the cell cycle-associated proteins Chk1, pChk1ser345, and Cyclin B was analyzed by western blot. Results Loratadine pre-treatment of exponentially growing cells (75 μM, 24 hours increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95. However, treatment of plateau phase cells also yielded a DMF of 1.3 suggesting that mechanisms other than cell cycle arrest also contribute to loratadine-mediated radiation modification. Like irradiation, loratadine initially induced G2/M arrest and activation of the cell-cycle associated protein Chk1 to pChk1ser345, however a subsequent decrease in expression of total Chk1 and Cyclin B correlated with abrogation of the G2/M checkpoint. Analysis of DNA repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA damage in loratadine-treated cells in addition to enhanced radiation-induced damage. Taken together, these data suggest that the observed effects of loratadine are multifactorial in that loratadine 1 directly damages DNA, 2 activates Chk1 thereby promoting G2/M arrest making cells more susceptible to radiation-induced DNA damage and, 3 downregulates total Chk1 and Cyclin B abrogating the radiation-induced G2/M checkpoint and allowing cells to re-enter the cell cycle despite the persistence of

  6. [A case of chronic inorganic mercury poisoning with progressive intentional tremor and remarkably prolonged latency of P300].

    Science.gov (United States)

    Shikata, E; Mochizuki, Y; Oishi, M; Takasu, T

    1998-12-01

    A 59-year-old man showed slowly progressive intentional tremor for 40 years prior to first visit to us in 1996. He was exposed to mercury vapor for about 3 years (1956-1959) and the diagnosis of chronic inorganic mercury poisoning was made. Hasegawa dementia scale-revised (HDS-R), mini-mental state (MMS) examination and P300 examination were performed. HDS-R and MMS were within normal range but the latency of P300 was remarkably prolonged. His tremor was considered to be due to chronic inorganic poisoning because there were no other causes and the frequency of his tremor was 3-4 Hz. which was lower than that in essential tremor. The prolonged P300 latency was also considered to be due to the same cause because there were no other causes and the head MRI were normal. Chronic inorganic mercury poisoning has been reported to produce organic changes in the brain and P300 is considered to be useful to detect these changes.

  7. Progressive pituitary hormone deficiency following radiation therapy in adults; Deficiencia progressiva dos hormonios adeno-hipofisarios apos radioterapia em adultos

    Energy Technology Data Exchange (ETDEWEB)

    Loureiro, Rafaela A.; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia]. E-mail: rafaela_loureiro@hotmail.com

    2004-10-01

    Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

  8. Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Michael S. [Monroe Carell Jr. Children' s Hospital at Vanderbilt, Department of Pediatrics, Nashville, TN (United States); Chadha, Ashley D. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Carroll, Clinton M.; Borinstein, Scott C. [Vanderbilt University School of Medicine, Division of Hematology and Oncology, Department of Pediatrics, Nashville, TN (United States); Young, Lisa R. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Nashville, TN (United States)

    2015-07-15

    Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. (orig.)

  9. Recent progress in the development of large area silica aerogel for use as RICH radiator in the Belle II experiment

    CERN Document Server

    Tabata, Makoto; Kawai, Hideyuki; Nishida, Shohei; Sumiyoshi, Takayuki

    2014-01-01

    We report recent progress in the development of large-area hydrophobic silica aerogels for use as radiators in the aerogel-based ring-imaging Cherenkov (A-RICH) counter to be installed in the forward end cap of the Belle II detector, which is currently being upgraded at the High Energy Accelerator Research Organization (KEK), Japan. The production of approximately 450 aerogel tiles with refractive indices of either 1.045 or 1.055 was completed in May, 2014, and the tiles are now undergoing optical characterization. Installation of the aerogels was tested by installing them into a partial mock-up of the support structure.

  10. Radiation carcinogenesis. Progress report VI, 16 May 1978--15 May 1979

    Energy Technology Data Exchange (ETDEWEB)

    Warren, S.; Gates, O.

    1979-01-01

    Asbestos fibers, Canadian and Rhodesian chrysotile, have induced mesotheliomas and pleural plaques in mice and rats. The pathogenesis of the lesions is being studied. Proliferation of the adrenal cortical A cells is accelerated in time and enhanced in extent by ionizing radiation in female RAP mice. The development of cortical tumors was significantly correlated with extensive A cell proliferation. Whole-body protracted doses, above 500 rads, were followed by a 9% tumor incidence. Endocrine neoplasia in mice appears related to functional ties between several endocrines particularly adrenal, ovary, and pituitary. A study of the spontaneous benign and malignant tumors ocurring in control NEDH rats has provided background for the tumorigenic effects of radiation and also of altered hormonal internal milieu. Begin tumors have been produced by radiation in a wide variety of tissues for the first time, providing data as to the relative responsiveness in benign tumor production of various tissues to a dose of 1000 rads. The hormonal changes secondary to parabiosis and hemi-irradiation of the pair are important. A radiation-induced functioning pheochromocytoma causing hypertension and death has been found widely useful by investigators. A radiation-induced malignant insulinoma has also been widely used, and insulin-producing DNA from it has served in the hands of others through genetic engineering to provide an insulin-producing strain of the bacillus E. coli.

  11. Progress in Projecting Solar Radiation at the Earth's Surface in Climate Models

    Science.gov (United States)

    Collins, W.; Fildier, B.; Feldman, D.

    2015-12-01

    Projecting changes in solar radiation at the Earth's surface in futureclimates is a critical input to forecast surface irradiance for solarenergy. We demonstrate the current state of the art using theensemble of opportunity assembled for the Coupled ModelIntercomparison Project (CMIP5) and the Fifth Assessment Report (AR5)of the Intergovernmental Panel on Climate Change (IPCC). The reliability of these projections depends upon the accuracy of theunderlying radiation codes, the fidelity of these codes to themeasured optical properties of key radiatively active atmosphericconstituents, and the realism of future projections of theseatmospheric constituents. These constituents include aerosols,clouds, water vapor, greenhouse gases that absorb near-infraredsunlight. Since the realism of future projections of anthropogenicaerosol species is contingent on the underlying scenario, we focus onthe other challenges in forecasting surface irradiance. Regarding accuracy, we demonstrate that current GCM shortwaveparameterizations often exhibit quite small errors relative tobenchmark radiative transfer codes. In addition, recent work hasbracketed the uncertainties in solar irradiance associated withcomplex cloud geometries. There is also an emerging consensus howcloud radiative effects will evolve in a warmer climate. However,there is evidence that current GCM codes still exhibit systematicerrors in the near-infrared water vapor bands, particularly for moistsub-tropical atmospheres. These errors will become more acute aswater vapor feedbacks, combined with global warming, increase thetotal precipitable water in the Earth's atmosphere.

  12. Progress in the treatment of chronic hepatitis B: long-term experience with adefovir dipivoxil.

    Science.gov (United States)

    Delaney, William E

    2007-05-01

    Most chronic hepatitis B patients do not undergo a curative response to interferon-alpha or nucleoside/nucleotide-based regimens and require long-term therapy. Long-term safety, efficacy and resistance profiles of hepatitis B virus (HBV) drugs are therefore crucial issues for patient management. Adefovir dipivoxil is a nucleotide prodrug indicated for the treatment of patients with hepatitis B e antigen positive or hepatitis B e antigen negative chronic hepatitis B, lamivudine-resistant HBV infection, HBV infection pre- or post-liver transplantation, or HlV co-infection. Long-term data from clinical trials of up to 5 years duration of adefovir dipivoxil have recently become available and are reviewed here. These data demonstrate that adefovir dipivoxil therapy results in sustained efficacy and safety in the majority of patients after multiple years of treatment. The efficacy of adefovir dipivoxil in treating lamivudine-resistant HBV and the delayed emergence of adefovir resistance are key factors contributing to the durable response achieved in broad groups of chronic hepatitis B patients.

  13. A resistant starch fiber diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

    Science.gov (United States)

    Inflammation is a constant feature and a major mediator of CKD progression. It is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2-...

  14. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease

    Science.gov (United States)

    Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammoni...

  15. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

    Science.gov (United States)

    Pfeffer, Gerald; Gorman, Gráinne S; Griffin, Helen; Kurzawa-Akanbi, Marzena; Blakely, Emma L; Wilson, Ian; Sitarz, Kamil; Moore, David; Murphy, Julie L; Alston, Charlotte L; Pyle, Angela; Coxhead, Jon; Payne, Brendan; Gorrie, George H; Longman, Cheryl; Hadjivassiliou, Marios; McConville, John; Dick, David; Imam, Ibrahim; Hilton, David; Norwood, Fiona; Baker, Mark R; Jaiser, Stephan R; Yu-Wai-Man, Patrick; Farrell, Michael; McCarthy, Allan; Lynch, Timothy; McFarland, Robert; Schaefer, Andrew M; Turnbull, Douglass M; Horvath, Rita; Taylor, Robert W; Chinnery, Patrick F

    2014-05-01

    Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal

  16. Time of progression to osteopenia/osteoporosis in chronically HIV-infected patients: screening DXA scan.

    Directory of Open Access Journals (Sweden)

    Eugenia Negredo

    Full Text Available BACKGROUND: Algorithms for bone mineral density (BMD management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA scan should be performed by assessing time of progression to osteopenia/osteoporosis. METHODS: All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis was assessed using the Kaplan-Meier method. Strata (tertiles were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test. RESULTS: Of 391 patients (1,639 DXAs, 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6% with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: "low-risk" (baseline minimum T score >-0.2 SD, "middle-risk" (between -0.2 and -0.6 SD, and "high-risk" (from -0.6 to -1 SD; median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (p8.5 years. Progression time was >8.2 years in "low-risk" tertile (T score between -1.1 and -1.6 SD, >8.5 years in "middle-risk" (between -1.6 and -2, and 3.2 years in "high-risk" (from -2 to -2.4 (p<0.0001. CONCLUSIONS: Our results may help to define the BMD testing interval. The lowest T score tertiles would suggest recommending a subsequent DXA in 1-2 years; in the highest tertiles, ≥6 years. Early intervention in patients with bone demineralization could reduce fracture-related morbidity/mortality.

  17. Uremic Solutes in Chronic Kidney Disease and Their Role in Progression

    Science.gov (United States)

    van den Brand, Jan A. J. G.; Mutsaers, Henricus A. M.; van Zuilen, Arjan D.; Blankestijn, Peter J.; van den Broek, Petra H.; Russel, Frans G. M.; Masereeuw, Rosalinde; Wetzels, Jack F. M.

    2016-01-01

    Background To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Methods Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. Results In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Conclusions Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated. PMID:28033375

  18. Development of a plasma panel radiation detector: recent progress and key issues

    CERN Document Server

    Silver, Yiftah; Beene, James R; Benhammou, Yan; Ben-Moshe, Meny; Chapman, J W; Dai, Tiesheng; Etzion, Erez; Ferretti, Claudio; Guttman, Nir; Friedman, Peter S; Levin, Daniel S; Ritt, S; Varner, Robert L; Weaverdyck, Curtis; Zhou, Bing

    2012-01-01

    A radiation detector based on plasma display panel technology, which is the principal component of plasma television displays is presented. Plasma Panel Sensor (PPS) technology is a variant of micropattern gas radiation detectors. The PPS is conceived as an array of sealed plasma discharge gas cells which can be used for fast response (O(5ns) per pixel), high spatial resolution detection (pixel pitch can be less than 100 micrometer) of ionizing and minimum ionizing particles. The PPS is assembled from non-reactive, intrinsically radiation-hard materials: glass substrates, metal electrodes and inert gas mixtures. We report on the PPS development program, including simulations and design and the first laboratory studies which demonstrate the usage of plasma display panels in measurements of cosmic ray muons, as well as the expansion of experimental results on the detection of betas from radioactive sources.

  19. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1983-03-01

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD.

  20. Chronic eosinophilic leukemia with FIP1L1-PDGFRA transcripts after occupational and therapeutic exposure to radiation

    Directory of Open Access Journals (Sweden)

    Gueorgui Balatzenko

    2011-10-01

    Full Text Available We present for the first time a 40-year-old male patient with a 20 year history of occupational exposure to radiation as a nuclear power plant worker, who developed FIP1L1-PDGFRA-positive chronic eosinophilic leukaemia 27 months after radiotherapy for testicular seminoma. After an one-year history of dry cough, itching and night sweats, the patient presented with an elevated leukocyte count with absolute eosinophilia of 14.2x109/L, bone marrow and lymph node involvement. Treatment with Imatinib was initiated, resulting in complete haematological remission at the sixth month and complete molecular response by nested primers reverse transcription polymerase chain reaction – at the end of the first year. This case contributes for the clinical heterogeneity of FIP1L1-PDGFA – positive myeloproliferative neoplasms and the possible role of occupational and therapeutic radiation, raising the question if one or both of them might be the causative factor.

  1. Ionizing radiation and risk of chronic lymphocytic leukemia in the 15-country study of nuclear industry workers

    DEFF Research Database (Denmark)

    Vrijheid, Martine; Cardis, Elisabeth; Ashmore, Patrick

    2008-01-01

    In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external...... in this cohort. The relative risk (RR) at an occupational dose of 100 mSv compared to 0 mSv was 0.84 (95% CI 0.39, 1.48) under the assumption of a 10-year exposure lag. Analyses of longer lag periods showed little variation in the RR, but they included very small numbers of cases with relatively high doses...

  2. Cellular proliferation and regeneration following tissue damage. Progress report. [X radiation; rabbit lenses

    Energy Technology Data Exchange (ETDEWEB)

    Harding, C.V.

    1977-01-01

    Studies were conducted on the following research projects: effects of x radiation on rabbit lenses; DNA synthesis and mitosis in cultured lenses; serum dependency and actinomycin D sensitivity; changes in ultrastructure; injury-induced growth of vascular endothelium; corneal neovascularization following injury; and human cataractous lenses. (HLW)

  3. Progress in high pressure EDXD system and research at Beijing Synchrotron Radiation Facility

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The synchrotron radiation from a new wiggler of BEPC has been used to high pressure research. Upgraded DAC apparatus and EDXD system have been operated to determine the pressure-induced phase transition of materials at BSRF since June 1998. The improved performance of the system and the preliminary results of the research were described.

  4. Progress Towards Optimally Efficient Schemes for Monte Carlo Thermal Radiation Transport

    Energy Technology Data Exchange (ETDEWEB)

    Smedley-Stevenson, R P; Brooks III, E D

    2007-09-26

    In this summary we review the complementary research being undertaken at AWE and LLNL aimed at developing optimally efficient algorithms for Monte Carlo thermal radiation transport based on the difference formulation. We conclude by presenting preliminary results on the application of Newton-Krylov methods for solving the Symbolic Implicit Monte Carlo (SIMC) energy equation.

  5. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Nosratola D Vaziri

    Full Text Available Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control or high fermentable fiber (amylose maize resistant starch, HAM-RS2 for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.

  6. Chronic Progressive Neurodegeneration in a transgenic mouse model of Prion disease

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2016-11-01

    Full Text Available Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic protein without accompanying neurodegeneration pattern. The lack of a comprehensive model hinders the efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice, mimicking for genetic Creutzfeldt-Jacob disease as compared to age matched wild type mice. Mice exhibited a neurodegenerative process indicated by progressive reduction in cortical neurons and synapses, starting at age of 4-6 months, in accordance with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with progressive neurological disease, indicating these mice can serve as a model for neurodegenerative diseases.

  7. Helicobacter pylori infection may increase the risk of progression of chronic hepatitis B disease among the Chinese population: a meta-analysis

    OpenAIRE

    Juan Wang; Ruo-Chan Chen; Yi-Xiang Zheng; Shu-Shan Zhao; Ning Li; Rong-Rong Zhou; Yan Huang; Ze-Bing Huang; Xue-Gong Fan

    2016-01-01

    Objectives: Helicobacter pylori is a bacterium that infects over 50% of the human population worldwide. An increasing number of studies have demonstrated that H. pylori may cause liver diseases, and the underlying relationship between H. pylori infection and chronic hepatitis B has attracted much attention. This study aimed to examine the association between H. pylori infection and the progression of chronic hepatitis B in the Chinese population. Methods: A search was performed of the PubM...

  8. A microsimulation model for the development and progression of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Tan, Emma; Boessen, Ruud; Fishwick, David; Klein Entink, Rinke; Meijster, Tim; Pronk, Anjoeka; van Duuren-Stuurman, Birgit; Warren, Nick

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is a chronic lung disease that is thought to affect over one million people in Great Britain. The main factor contributing to the development of COPD is tobacco smoke. This paper presents a microsimulation model for the development of COPD, incorporating population dynamics and trends in smoking. The model simulates a population longitudinally throughout their lifetimes, providing projections of future COPD prevalence and evaluation of the effects of changes in risk factor prevalence such as smoking. Sensitivity analysis provides information on the most influential model parameters. The model-predicted prevalence of COPD in 2040 was 17% in males over the age of 35 years (13% amongst non-smokers and 22% amongst smokers), and a modest decline over the next 25 years due to recent trends in smoking rates. The simulation model provides us with valuable information on current and future trends in COPD in Great Britain. It was developed primarily to enable easy extension to evaluate the effects of occupational and environmental exposures on lung function and the prevalence of COPD and to allow evaluation of interventions, such as introducing health surveillance or policy changes. As longitudinal studies for investigating COPD are difficult due to the lengthy follow-up time required and the potentially large number of drop-outs, we anticipate that the model will provide a valuable tool for health impact assessment. An extended model for occupational exposures is under development and will be presented in a subsequent paper.

  9. Progression of Tubulointerstitial Fibrosis and the Chronic Kidney Disease Phenotype – Role of Risk Factors and Epigenetics

    Directory of Open Access Journals (Sweden)

    Timothy D. Hewitson

    2017-08-01

    Full Text Available Although the kidney has capacity to repair after mild injury, ongoing or severe damage results in scarring (fibrosis and an associated progressive loss of kidney function. However, despite its universal significance, evidence highlights a population based heterogeneity in the trajectory of chronic kidney disease (CKD in these patients. To explain the heterogeneity of the CKD phenotype requires an understanding of the relevant risk factors for fibrosis. These factors include both the extrinsic nature of injury, and intrinsic factors such as age, gender, genetics, and perpetual activation of fibroblasts through priming. In many cases an additional level of regulation is provided by epigenetic mechanisms which integrate the various pro-fibrotic and anti-fibrotic triggers in fibrogenesis. In this review we therefore examine the various molecular and structural changes of fibrosis, and how they are influenced by extrinsic and intrinsic factors. Our aim is to provide a unifying hypothesis to help explain the transition from acute to CKD.

  10. Chronic effects of ultraviolet-B radiation on growth and cell volume of Phaeodactylum tricornutum (Bacillariophyceae)

    Energy Technology Data Exchange (ETDEWEB)

    Behrenfeld, M.J. (AScI Corp., Newport, OR (United States)); Hardy, J.T. (Western Washington Univ., Bellingham (United States)); Lee, H. II (Environmental Protection Agency, Newport, OR (United States))

    1992-12-01

    Cultures of the temperate estuarine diatom, Phaeodactylum tricornutum Bohlin (NEPCC Clone 31), were grown under ambient intensities of ultraviolet-A radiation (UVAR), photosynthetically active radiation (PAR), and various intensities of ultraviolet-B radiation (UVBR; 290-320 nm). Growth rates and cell volumes were monitored for 36 d. UVBR decreased growth rates and increased cell volumes. Sensitivity of growth to UVBR increased with time. Growth rates of P. tricornutum decreased with increasing ratios of UVBR:UVAR + PAR. 25 refs., 4 figs., 1 tab.

  11. Comparative study of radiation, chemical, and aging effects on viral transformation. Annual progress report, 1975

    Energy Technology Data Exchange (ETDEWEB)

    Coggin, J.H. Jr.

    1976-03-31

    Progress is reported on the following research projects: evaluation of isotopic antiglobulin test (IAT) to detect tumor associated antigens using antisera induced by x-irradiated tumor cells; development of cytotoxic antibody for embryonic antigens (EA); acrylamide gel cell culture assay for transformation; and evaluation of 3-MCA induced sarcomas for TSTA and cross-reacting antigens. (HLW)

  12. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn;

    2010-01-01

    The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard...

  13. Time-updated systolic blood pressure and the progression of chronic kidney disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

    Science.gov (United States)

    Anderson, Amanda H; Yang, Wei; Townsend, Raymond R; Pan, Qiang; Chertow, Glenn M; Kusek, John W; Charleston, Jeanne; He, Jiang; Kallem, RadhaKrishna; Lash, James P; Miller, Edgar R; Rahman, Mahboob; Steigerwalt, Susan; Weir, Matthew; Wright, Jackson T; Feldman, Harold I

    2015-01-01

    Background Blood pressure (BP) is often inadequately controlled in patients with chronic kidney disease (CKD). Previous reports of the longitudinal association between achieved level of BP and end-stage renal disease (ESRD) have not incorporated time-updated BP with appropriate adjustment for known confounders. Objective To assess the association between baseline and time-updated systolic BP (SBP) with the progression of CKD. Design Observational, prospective cohort study (ClinicalTrials.gov identifier: NCT00304148) Setting Seven US clinical centers Patients Participants of the Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,708) followed for a median (25th, 75th percentiles) of 5.7 (4.6, 6.7) years Measurements The mean of three seated SBP measurements were used as the visit-specific SBP. SBP was time-updated as the mean of that visit and all prior visits. Outcomes were ESRD and the composite renal endpoint of ESRD (dialysis or transplantation) or halving of the estimated glomerular filtration rate (eGFR). Analyses investigating baseline and time-updated SBP utilized traditional Cox proportional hazards models and marginal structural models, respectively. Results SBP was ≥130 mmHg at all study visits in 19.2% of participants, and ≥140 mmHg in 10.6%. The hazard ratio (95% confidence interval) for ESRD among participants with SBP 130–139 mmHg, compared to SBP <120 mmHg, was 1.46 (1.13–1.88) using only baseline data, and was 2.37 (1.48–3.80) using all available time-updated data. Among those with SBP ≥140 mmHg, corresponding hazard ratios were 1.46 (1.18–1.88) and 3.37 (2.26–5.03), respectively. Limitations SBP was measured once annually, and the CRIC Study cohort is not a random sample. Conclusions Among participants in the CRIC Study, time-updated SBP over 130 mmHg was more strongly associated with progression of CKD than analyses based on baseline SBP. Funding The CRIC Study is funded under cooperative agreements from the National Institute of

  14. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  15. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  16. Increased renal versican expression is associated with progression of chronic kidney disease.

    Science.gov (United States)

    Rudnicki, Michael; Perco, Paul; Neuwirt, Hannes; Noppert, Susie-Jane; Leierer, Johannes; Sunzenauer, Judith; Eder, Susanne; Zoja, Carlamaria; Eller, Kathrin; Rosenkranz, Alexander R; Müller, Gerhard A; Mayer, Bernd; Mayer, Gert

    2012-01-01

    Novel prognostic markers for progression of kidney disease are needed to distinguish patients who might benefit from a more aggressive nephroprotective therapy. Expression of the proteoglycan versican was evaluated in renal transcriptomics profiles and in an independent set of 74 renal biopsies. Versican levels were correlated to histologic damage scores and to renal outcome, and versican expression and regulation was evaluated in vitro. In transcriptomics profiles of renal tissue versican was positively correlated with (i) histological parameters in kidney biopsies, (ii) progressive decline of renal function in proteinuric kidney diseases, and (iii) impaired renal function and histology scores in diabetic nephropathy. In an independent cohort of 74 biopsies of glomerular diseases renal RNA levels of versican isoforms V0 and V1, but not V2 and V3 correlated significantly with creatinine after a mean follow up time of 53 months. Versican isoforms V0 and V1 together with serum creatinine at time of biopsy and the degree of glomerulosclerosis predicted 20% and 24% of the variability of creatinine at follow up, which was significantly more than serum creatinine and histological parameters alone (16%). However, when patients with acute kidney failure at time of biopsy (n = 5) were excluded, the additive predictive value of versican V1 was only marginally higher (35%) than creatinine and glomerulosclerosis alone (34%). Versican isoforms V0 and V1 were primarily expressed in vitro in proximal tubule cells and in fibroblasts. The results in humans were confirmed in three rodent models of kidney disease, in which renal versican expression was significantly upregulated as compared to corresponding controls. These data show for the first time an association of renal versican isoform V0 and V1 expression with progressive renal disease.

  17. Increased renal versican expression is associated with progression of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Michael Rudnicki

    Full Text Available Novel prognostic markers for progression of kidney disease are needed to distinguish patients who might benefit from a more aggressive nephroprotective therapy. Expression of the proteoglycan versican was evaluated in renal transcriptomics profiles and in an independent set of 74 renal biopsies. Versican levels were correlated to histologic damage scores and to renal outcome, and versican expression and regulation was evaluated in vitro. In transcriptomics profiles of renal tissue versican was positively correlated with (i histological parameters in kidney biopsies, (ii progressive decline of renal function in proteinuric kidney diseases, and (iii impaired renal function and histology scores in diabetic nephropathy. In an independent cohort of 74 biopsies of glomerular diseases renal RNA levels of versican isoforms V0 and V1, but not V2 and V3 correlated significantly with creatinine after a mean follow up time of 53 months. Versican isoforms V0 and V1 together with serum creatinine at time of biopsy and the degree of glomerulosclerosis predicted 20% and 24% of the variability of creatinine at follow up, which was significantly more than serum creatinine and histological parameters alone (16%. However, when patients with acute kidney failure at time of biopsy (n = 5 were excluded, the additive predictive value of versican V1 was only marginally higher (35% than creatinine and glomerulosclerosis alone (34%. Versican isoforms V0 and V1 were primarily expressed in vitro in proximal tubule cells and in fibroblasts. The results in humans were confirmed in three rodent models of kidney disease, in which renal versican expression was significantly upregulated as compared to corresponding controls. These data show for the first time an association of renal versican isoform V0 and V1 expression with progressive renal disease.

  18. Progressive or degressive compression pressure profile in patients with chronic venous disorders of the lower limb

    Directory of Open Access Journals (Sweden)

    Giovanni Mosti

    2014-03-01

    Full Text Available Graduated compression devices are considered the standard care for management of venous and lymphatic disorders. Recently compression devices exerting a pressure over the calf higher than over the ankle have been proved to be more effective than traditional graduated devices in increasing the impaired ejection fraction (EF from the lower leg in patients with venous disease. Aim of this work is presenting an overview of the new concept on progressive compression, its potential benefits and limits. In different series of tests, the EF from the lower leg was assessed in 70 patients with severe reflux in the great saphenous vein (GSV. EF was measured by strain gauge plethysmography, in baseline conditions and after applying graduated compression devices or the new inversely graduated or progressive compression (PC devices. The interface pressure was recorded, simultaneously with the EF, both in the gaiter area (B1 point and at the calf (C point in order to assess the compression pressure profile. EF, severely impaired in patients with GSV reflux, was increased by compression. So called PC devices (both PC elastic stocking and PC inelastic bandages were significantly more effective than graduated compression in increasing the ejection fraction. The higher the pressure on the calf the higher the EF improvement. Maintaining the same strong pressure over the calf by means of two progressive stockings and increasing the pressure only over the calf to restore a graduated compression didn’t improve the EF. To improve venous pumping function in the ambulant patient stronger compression of the calf is more effective than graduated compression. This can be explained by the higher amount of blood volume pooled in the calf veins.

  19. Profile of central and effector memory T cells in the progression of chronic human chagas disease.

    Directory of Open Access Journals (Sweden)

    Jacqueline Araújo Fiuza

    Full Text Available BACKGROUND: Chronic Chagas disease presents several different clinical manifestations ranging from asymptomatic to severe cardiac and/or digestive clinical forms. Several studies have demonstrated that immunoregulatory mechanisms are important processes for the control of the intense immune activity observed in the chronic phase. T cells play a critical role in parasite specific and non-specific immune response elicited by the host against Trypanosoma cruzi. Specifically, memory T cells, which are basically classified as central and effector memory cells, might have a distinct migratory activity, role and function during the human Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Based on the hypothesis that the disease severity in humans is correlated to the quality of immune responses against T. cruzi, we evaluated the memory profile of peripheral CD4(+ and CD8(+ T lymphocytes as well as its cytokine secretion before and after in vitro antigenic stimulation. We evaluated cellular response from non-infected individuals (NI, patients with indeterminate (IND or cardiac (CARD clinical forms of Chagas disease. The expression of CD45RA, CD45RO and CCR7 surface molecules was determined on CD4(+ and CD8(+ T lymphocytes; the pattern of intracellular cytokines (IFN-gamma, IL-10 synthesized by naive and memory cells was determined by flow cytometry. Our results revealed that IND and CARD patients have relatively lower percentages of naive (CD45RA(high CD4(+ and CD8(+ T cells. However, statistical analysis of ex-vivo profiles of CD4(+ T cells showed that IND have lower percentage of CD45RA(high in relation to non-infected individuals, but not in relation to CARD. Elevated percentages of memory (CD45RO(high CD4(+ T cells were also demonstrated in infected individuals, although statistically significant differences were only observed between IND and NI groups. Furthermore, when we analyzed the profile of secreted cytokines, we observed that CARD patients

  20. ELDOR investigations of radiation processes. Annual progress report, 1981-1982

    Energy Technology Data Exchange (ETDEWEB)

    Kispert, L.D.

    1982-01-01

    Purpose is to study how the lattice affects primary radiation and photochemical processes in irradiated organic solids. EPR spectral analysis is facilitated by combining ELDOR (electron-electron double resonance) with ENDOR and electron spin echo. Studies carried out during this period were on doped poly(p-phenylene sulfide) and poly(p-phenylene), and on the radical CF/sub 2/CONH/sub 2/. Other studies are summarized in abstracts. 105 references. (DLC)

  1. Protective Effect of Topically Applied Polypeptide from Chlamys farreri Against Ultraviolet Radiation-Induced Chronic Skin Damage in Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    迟明亮; 曹鹏利; 于国英; 朱莉; 王跃军; 王春波

    2003-01-01

    Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed:(1)PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner.(2)PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px.(3)The differences among the PCF groups and UV model group were significant (P<0.05, P<0.01). These results indicated that topical application of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

  2. Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure

    Science.gov (United States)

    Wilson Tang, Wai Hong; Tong, Wilson; Shrestha, Kevin; Wang, Zeneng; Levison, Bruce S.; Delfraino, Brian; Hu, Bo; Troughton, Richard W.; Klein, Allan L.; Hazen, Stanley L.

    2008-01-01

    Aims To investigate the association of arginine methylation with myocardial function and prognosis in chronic systolic heart failure patients. Methods and results Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as N-mono-methylarginine (MMA) and methyl-lysine, were simultaneously measured by tandem mass spectrometry in 132 patients with chronic systolic heart failure with echocardiographic evaluation and follow-up. Increasing ADMA and SDMA levels were associated with elevated natriuretic peptide levels (both P < 0.001), and increasing SDMA levels were associated with worsening renal function (P < 0.001). Higher plasma levels of methylated arginine metabolites (but not methyl-lysine) were associated with the presence of left ventricular (LV) diastolic dysfunction (E/septal E′, Spearman's r = 0.31–0.36, P < 0.001). Patients taking beta-blockers had lower ADMA levels than those not taking beta-blockers [0.42 (0.33, 0.50) vs. 0.51 (0.40, 0.58), P < 0.001]. Only increasing ADMA levels were associated with advanced right ventricular (RV) systolic dysfunction. Elevated ADMA levels remained a consistent independent predictor of adverse clinical events (hazard ratio = 1.64, 95% CI: 1.20–2.22, P = 0.002). Conclusion In chronic systolic heart failure, accumulation of methylated arginine metabolites is associated with the presence of LV diastolic dysfunction. Among the methylated derivatives of arginine, ADMA provides the strongest independent prediction of disease progression and adverse long-term outcomes. PMID:18687662

  3. The role of ATM mutations and 11q deletions in disease progression in chronic lymphocytic leukemia.

    Science.gov (United States)

    Stankovic, Tatjana; Skowronska, Anna

    2014-06-01

    Abstract ATM gene alteration is a frequent event in pathogenesis of chronic lymphocytic leukemia (CLL) and occurs as monoallelic loss in the form of 11q23 deletion, with and without mutation in the remaining ATM allele. ATM is a principal DNA damage response gene and biallelic ATM alterations lead to ATM functional loss and chemoresistance. The introduction of new therapies, such as intensive chemoimmunotherapy and inhibition of B-cell receptor (BCR) signaling, has changed clinical responses for the majority of CLL tumors including those with 11q deletion, but it remains to be determined whether these strategies can prevent clonal evolution of tumors with biallelic ATM alterations. In this review we discuss ATM function and the consequences of its loss during CLL pathogenesis, differences in clinical behavior of tumors with monoallelic and biallelic ATM alterations, and we outline possible approaches for targeting the ATM null CLL phenotype.

  4. Cutaneous changes in rats induced by chronic skin exposure to ultraviolet radiation and organophosphate pesticide

    OpenAIRE

    Fernandes,Tania Rita Moreno de Oliveira; Santos, Itamar; Korinsfky,Juliana Pedrosa; Silva,Benedyto Sávio Lima e; Carvalho,Luis Otávio; Plapler,Hélio

    2014-01-01

    PURPOSE: To study the possible potentiation of the carcinogenic effects of ultraviolet radiation associated with an organophosphate pesticide.METHODS: Forty Wistar rats were assigned into four groups (n=10 each) randomized according to the procedures: group A received only UVR-B radiation; group B, UVR-B for eight weeks followed by a seven week period of pesticide exposure; group C, UVR-B + pesticide concomitantly: group D, only pesticide application. At the end of the fifth, tenth and fiftee...

  5. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.

    Science.gov (United States)

    Woodruff, Prescott G; Agusti, Alvar; Roche, Nicolas; Singh, Dave; Martinez, Fernando J

    2015-05-02

    Chronic obstructive pulmonary disease (COPD) is a common, complex, and heterogeneous disorder that is responsible for substantial and growing morbidity, mortality, and health-care expense worldwide. Of imperative importance to decipher the complexity of COPD is to identify groups of patients with similar clinical characteristics, prognosis, or therapeutic needs, the so-called clinical phenotypes. This strategy is logical for research but might be of little clinical value because clinical phenotypes can overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal to match assessment with treatment choices, the latest iteration of guidelines from the Global Initiative for Chronic Obstructive Lung Disease reorganised treatment objectives into two categories: to improve symptoms (ie, dyspnoea and health status) and to decrease future risk (as predicted by forced expiratory volume in 1 s level and exacerbations history). This change thus moves treatment closer to individualised medicine with available bronchodilators and anti-inflammatory drugs. Yet, future treatment options are likely to include targeting endotypes that represent subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful in clinical practice, especially in patients in which clinical phenotype alone is insufficient to identify the underlying endotype. A few series of potential COPD endotypes and biomarkers have been suggested. Empirical knowledge will be gained from proof-of-concept trials in COPD with emerging drugs that target specific inflammatory pathways. In every instance, specific endotype and biomarker efforts will probably be needed for the success of these trials, because the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility to improve understanding of disease pathobiological

  6. Progressive multifocal leukoencephalopathy complicating untreated chronic lymphatic leukemia: case report and review of the literature.

    Science.gov (United States)

    Di Pauli, Franziska; Berger, Thomas; Walder, Alois; Maier, Hans; Rhomberg, Paul; Uprimny, Christian; Steurer, Michael; Stockhammer, Guenther

    2014-08-01

    A 58-year old female with a four-year history of previously untreated CLL at Binet stage A complained about word finding problems, impaired vision, and gait unsteadiness. Concerning her CLL she was asymptomatic and had never required any specific treatment. Her neurological examination disclosed cognitive alterations, homonyme hemianopia to the right, aphasia, and mild right-sided hemiparesis. Cerebral MRI showed a hyperintense lesion on T2 weighted images without contrast enhancement. CSF examination revealed normal findings, including CSF protein, cell count, cytology and PCR-analysis was negative for the presence of JC virus DNA. On follow-up MRI, performed 2 weeks later, the T2 lesion was further enlarging. Subsequent stereotactic brain biopsy was diagnostic for PML revealing abnormal oligodendrocytes staining positive against antibodies specific for simian vacuolating virus 40. In addition, repeated CSF analyses for JC-Virus DNA in the course of the disease became positive. After confirmation of diagnosis treatment with mirtazapine (30 mg/d) and mefloquine (250 mg/d) was initiated. Rapid clinical progression correlated to further worsening on MRI. Therefore this treatment was terminated after 16 days and the regime was changed to a five-day courses of cytarabine (2 mg/kg/d) combined with intrathecal administration of liposomal cytarabine (50 mg). Due to further clinical progression with global aphasia, blindness and severe right-sided hemiparesia, medication was stopped. The Patient died three and a half months after onset of symptoms.

  7. Successful alemtuzumab retreatment in progressive B-cell chronic lymphocytic leukemia: a multicenter survey in 30 patients.

    Science.gov (United States)

    Fiegl, Michael; Falkner, Florian; Steurer, Michael; Zojer, Niklas; Hopfinger, Georg; Haslbauer, Ferdinand; Winder, Guntram; Voskova, Daniela; Andel, Johannes; Lang, Alois; Brychtova, Yvona; Mayer, Jiri; Greil, Richard; Gastl, Günther

    2011-09-01

    Although retreatment with alemtuzumab in relapsing B-cell chronic lymphocytic leukemia (CLL) may be beneficial, there has thus far been no thorough analysis available on this topic. Data were collected from 30 chemotherapy-pretreated patients with progressive CLL who had received alemtuzumab twice in consecutive, distinct therapy lines. The median dose of alemtuzumab retreatment was 402 mg (range, 43-1,090 mg). Retreatment with alemtuzumab induced an overall response rate of 47%. From the start of alemtuzumab retreatment, median progression-free survival (PFS) and overall survival (OS) were 6.3 and 20.0 months, respectively. Response rates, PFS and OS upon alemtuzumab retreatment were correlated with response to initial alemtuzumab treatment, the time interval between the initial course of alemtuzumab and start of retreatment, and the hemoglobin concentration prior to retreatment. Reported toxicities from 24 cases included infections (50%), febrile reactions upon alemtuzumab administration (38%), exanthema (21%), and grade 4 neutropenia (13%) and thrombocytopenia (17%). We conclude that alemtuzumab retreatment represents an effective and tolerable therapeutic option for selected patients with CLL.

  8. TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes.

    Science.gov (United States)

    Lazarian, Gregory; Tausch, Eugen; Eclache, Virginie; Sebaa, Amel; Bianchi, Vincent; Letestu, Remi; Collon, Jean-Francois; Lefebvre, Valerie; Gardano, Laura; Varin-Blank, Nadine; Soussi, Thierry; Stilgenbauer, Stephen; Cymbalista, Florence; Baran-Marszak, Fanny

    2016-10-15

    TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next-generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases.

  9. Do frequent moderate exacerbations contribute to progression of chronic obstructive pulmonary disease in patients who are ex-smokers?

    Directory of Open Access Journals (Sweden)

    Dreyse J

    2015-03-01

    Full Text Available Jorge Dreyse,1 Orlando Díaz,1 Paula Repetto,2 Arturo Morales,1 Fernando Saldías,1 Carmen Lisboa11Department of Pulmonary Diseases, School of Medicine, 2School of Psychology, Pontificia Universidad Católica de Chile, Santiago, ChileBackground: In addition to smoking, acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease (COPD. However, these findings come from studies including active smokers, while results in ex-smokers are scarce and contradictory. The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second (FEV1 and impairment of functional and clinical outcomes in ex-smoking COPD patients.Methods: A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition. Evaluation included anthropometry, spirometry, inspiratory capacity, peripheral capillary oxygen saturation, severity of dyspnea, a 6-minute walking test, BODE (Body mass index, airflow Obstruction, Dyspnea, Exercise performance index, and quality of life (St George’s Respiratory Questionnaire and Chronic Respiratory Disease Questionnaire. Severity of exacerbation was graded as moderate or severe according to health care utilization. Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year. Random effects modeling, within hierarchical linear modeling, was used for analysis.Results: During follow-up, 419 (96% moderate acute exacerbations were registered. At baseline, frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index, and also showed greater impairment in inspiratory capacity, forced vital capacity, peripheral capillary oxygen saturation

  10. Expansion of NK cells and reduction of NKG2D expression in chronic lymphocytic leukemia. Correlation with progressive disease.

    Directory of Open Access Journals (Sweden)

    Leticia Huergo-Zapico

    Full Text Available The immune system may mediate anti-tumor responses in chronic lymphocytic leukemia (CLL which may affect disease progression and survival. In this study, we analyzed the immune characteristics of 99 consecutive previously diagnosed CLL patients and 50 healthy controls. The distribution of lymphocyte subsets at diagnosis was retrospectively analyzed. Compared with controls, leukemia patients showed an expansion of NK and CD8 T cells at diagnosis. The relative number of CD8 T cells at diagnosis was associated with time to treatment, suggesting that CD8 T cells may modify disease progression. The distribution of lymphocyte subsets was analyzed again when patients were enrolled in this study. The median time since these patients were diagnosed was 277 weeks. Compared with diagnosis, the absolute number of CD8 T cells significantly decreased in these patients, reaching similar values to healthy controls; however NK cells kept significantly elevated overtime. Nevertheless, NK cells showed an impaired expression of NKG2D receptor and a defective cytotoxic activity. This down-regulation of NKG2D expression was further enhanced in patients with advanced and progressive disease. Additionally, membrane NKG2D levels significantly decreased on CD8 T cells, but a significant increase of NKG2D+CD4+ T cells was observed in CLL patients. The cytotoxic activity of NK cells was diminished in CLL patients; however the treatments with IL-2, IL-15, IL-21 and lenalidomide were able to restore their activity. The effect of IL-2 and IL-15 was associated with the increase of NKG2D expression on immune cells, but the effect of IL-21 and lenalidomide was not due to NKG2D up-regulation. The expansion of NK cells and the reversibility of NK cell defects provide new opportunities for the immunotherapeutic intervention in CLL.

  11. NOS3 tagSNPs does not modify the chronic kidney disease progression in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Ramanathan, Gnanasambandan; Periyasamy, Soundararajan; Lakkakula, Bhaskar Vks

    2014-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary and progressive renal disorder. It is also recognised as the most frequent genetic cause of chronic kidney diseases (CKD). In the present study, four tagging SNPs and two more well studied polymorphisms (Intron 4 VNTR and Glu298Asp) the NOS3 gene were investigated to unravel the potential modifier effect of NOS3 gene on the progression of CKD in ADPKD. A total of 102 ADPKD patients and 106 controls were selected for the study. The tagSNPs and Glu298Asp polymorphisms were genotyped using FRET-based KASPar method and intron-4 VNTR by polymerase chain reaction electrophoresis. The genotypes and haplotypes in the controls and ADPKD subjects were analysed by χ(2) tests and haploview software. Mantel-Haenszel stratified and univariate analyses were performed to estimate the influence of different genotypes between different CKD stages and hypertension. The tagSNPs of NOS3 genotypes and haplotypes did not exhibit any significant differences between controls and ADPKD patients. The significant linkage disequilibrium was observed between the rs3918184 and rs2853796 by forming LD block. In univariate analysis, the age and family history of Diabetes mellitus (DM) showed significant association with advancement of CKD, but not with the eNOS polymorphisms. Our data suggests that there is no evidence for the involvement of NOS3 tag SNPs in the progression to CKD in ADPKD patients. A systematic study using well validated functional SNPs is necessary to clarify the role of the NOS3 gene in the development of CKD in ADPKD. © 2014 Asian Pacific Society of Nephrology.

  12. Progress on the Flash X-Ray Optical Transition Radiation Diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    Tang, V; Houck, T; Brown, C

    2008-03-30

    This document summarizes the Flash X-Ray accelerator (FXR) optical transition radiation (OTR) spot-size diagnostics efforts in FY07. During this year, new analysis, simulation, and experimental approaches were utilized to interpret OTR spot data from both dielectric foils such as Kapton (VN type) and metal coated foils. Significant new findings of the intricacies involved in the diagnostic and of FXR operational issues were achieved. Geometry and temperature based effects were found to affect the beam image profiles from the OTR foils. These effects must be taken into account in order to deduce accurately the beam current density profile.

  13. Progress in radiation processing vol 1; food/environment/elastomers and polymers

    Energy Technology Data Exchange (ETDEWEB)

    Nablo, S.V. (ed.)

    1984-10-01

    This paper reports on the planning process for the conference on Radiation Processing. The final program was made up of six sessions on food applications, four on elastomers and polymers, two on environmental applications with eighteen additional sessions over the five day conference period. The emerging industrial applications of electron processing were highlighted in those sessions on graphics, magnetic media and semiconductors and there was some difficulty presenting a materials handling session due to the continuing reluctance of the equipment manufacturers to discuss proprietary details of web, sheet, formed product and wire handling machinery.

  14. Progress towards a more predictive model for hohlraum radiation drive and symmetry

    Science.gov (United States)

    Jones, Ogden

    2016-10-01

    The high flux model (HFM) was first developed to match emission levels observed from Au spheres illuminated symmetrically at the UR-LLE OMEGA laser. It utilizes a modern non-LTE atomic physics model and an electron thermal flux limiter of 0.15 or a non-local electron transport model. Shortly thereafter, the HFM was also found to better match the radiation drive observed through the laser entrance hole of laser-heated vacuum hohlraums on the NIF. Subsequent capsule implosion experiments driven by hohlraums filled with 1-1.6 mg/cc of He, having case-to-capsule ratios of 2.6, and pulse lengths 15-20 ns have been characterized by relatively large amounts of laser backscatter losses (up to 18% of the input laser energy). They have also utilized cross beam energy transfer (CBET) to transfer power to the lasers depositing energy near the hohlraum waist. When the HFM is applied to these experiments, the hohlraum x-ray drive is over-predicted by 20-30% during peak laser power, and the drive symmetry cannot be matched without making ad hoc corrections. More recent experiments using hohlraum fills from 0-0.6 mg/cc He, case-to-capsule ratios 3-4, and pulse lengths 6-10 ns have little or no CBET or backscatter and are in better agreement with calculations using the HFM, although discrepancies remain. Uncertainties remaining in the computational models of emissivity, laser absorption, heat transport, etc. used in our hydrodynamic codes can significantly affect predictions. In this work we test various physically-plausible adjustments or alternatives to these models in order to find a more predictive model for radiation drive in the regime with little or no backscatter or CBET. We utilize measurements of the radiation drive, shape and trajectory of the imploding shell, shape of the stagnated hot spot, and bang time in capsule implosions and spectroscopic measurements of the hohlraum plasma conditions to compare against high resolution hydrodynamic calculations using the various

  15. Research progress on Chronic Daily Headach e%慢性每日头痛的研究进展

    Institute of Scientific and Technical Information of China (English)

    乌欣蔚; 杨晓苏

    2014-01-01

    Chronic daily headache( CDH)is a commonly seen chronic headache with frequent attacking. CDH can be classified into chronic migraine,chronic tension-type headache,new daily persistent headache and persistent hemicrania based on the initial type of headache and clinical manifestation. Most CDH is transformed from paroxysmal headache,and its risk factors include obesity,baseline headache frequency and psychiatric comorbidity. The pathogenesis of primary CDH is closely related to pain sensitization of trigeminal sensory neuro. The prevention and treatment of CDH is vitally important because it brings continu-ous suffering to patients. Besides drug therapy,preventing risk factors and drug overdose are also important. The improvement of life quality and mental health should also be emphasized in the treatment of CDH. This article summarizes the research progress of CDH in terms of epidemiology,pathogenesis,diagnosis and treatment.%慢性每日头痛( CDH)是临床常见的频繁发作的慢性头痛。CDH根据初始头痛类型及临床表现可分为慢性偏头痛、慢性紧张性头痛、新发每日持续头痛和持续性偏侧头痛。CDH多由发作性头痛转化而来,肥胖、基线头痛频率、精神共患疾病等均是头痛慢性转化的危险因素。原发性CDH的发病机制与三叉神经感觉神经元敏感化有关。鉴于CDH给患者带来持久的痛苦,其防治十分重要。对于CDH的治疗,除了药物外,还应预防危险因素,杜绝药物过量,并注重生活习惯和心理卫生的改善。本文就CDH的流行病学、发病机制及诊治研究进展进行综述。

  16. Biostereometric Analysis Of Therapeutic Results In The Treatment Of Chronic, Progressive, Decompensating Postural Back Strain

    Science.gov (United States)

    Johnson, David M.

    1980-07-01

    A two year pilot program for biostereometric analysis of treatment effectiveness in five patients with chronic decompensating back strain has been completed. The patients came from the investigators family practice of osteopathic medicine. They all manifested objective signs of ligamentous and muscular strain of their postural biomechanics due to the combined effects of prior injury to the musculoskeletal system, gravity strain and the passage of time. Two of the patients were treated with osteopathic manipulative treatment plus a pelvic leverage treatment device developed by Martin Jungman, M.D. Two patients received osteopathic treatment alone and the fifth individual switched from control to full program status in the middle of the study after the second stereophotography recording. Signs and symptoms of all patients' gravity strain syndrome changed during the program. Those patients who had the full combination of treatment modalities showed the most positive and significant postural changes as demonstrated by the biostereometric technique developed and performed by the Department of Biostereometrics, Texas Institute of Rehabilitation and Research, Baylor College of Medicine, Houston, Texas. Improvement was clearly demonstrated more quickly than with the prior radiographic measuring methods. X-ray and other studies have also been done on this group. All of the data has not been processed yet in this program. The test patients have improved posture, muscle mass and tone, more stamina and reduced pain.

  17. Enhanced CD21 expression and shedding in chronic lymphatic leukemia: a possible pathomechanism in disease progression.

    Science.gov (United States)

    Low, Hui Zhi; Hilbrans, Dorothee; Schmidt-Wolf, Ingo G H; Illges, Harald

    2012-09-01

    CD21 is a 145-kDa membrane glycoprotein mainly expressed on B cells and follicular dendritic cells, and is involved in B-cell activation, survival and proliferation. CD21 can be cleaved to give soluble CD21 (sCD21), which is constantly shed in healthy persons. We show here that plasma sCD21 levels are higher, while B-cell surface CD21 expression levels are lower in B-cell chronic lymphocytic leukemia (B-CLL) patients, but not in multiple myeloma (MM) patients. High sCD21 levels in the blood are positively correlated to the number of cells with high CD21 surface expression and the relative amount of CD21 expressed on the B cells. B-CLL patients with swollen lymph nodes had higher amounts of CD21 high-expressing B cells, as well as CD21 low-expressing B cells, as compared to B-CLL patients without swollen lymph nodes.

  18. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Audette-Stuart, M., E-mail: stuartm@aecl.ca [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada); Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S. [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada)

    2011-06-15

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: > Frogs were collected from background and higher tritium level habitats. > The micronucleus assay was conducted on liver cells obtained from the frogs. > No detrimental effects were noted in frogs exposed to elevated tritium. > Adaptive responses were observed in frogs exposed to elevated tritium.

  19. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study

    OpenAIRE

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-01-01

    Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study correspondence: Corresponding author. Tel.: +43 5129003 70560; fax: +43 5129003 73560or73561. (Kronenberg, Florian) (Kronenberg, Florian) Division of Genetic Epidemiology; Department of Medical Genetics, Molecular and Clinical Pharmacology; Innsbruck Medical University - AUSTRIA (Stur...

  20. Association between Free Light Chain Levels, and Disease Progression and Mortality in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    European Uremic Toxin (EUTox Work Group

    2013-11-01

    Full Text Available Immunoglobulin free light chains (FLCs form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD. The aim of the present study was to measure FLC levels in patients at different CKD stages and to assess putative associations between FLC levels on one hand and biochemical/clinical parameters and mortality on the other. One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry assays and assays for FLC kappa (κ and lambda (λ and other uremic toxins were performed. Vascular calcification was evaluated using radiological techniques. The enrolled patients were prospectively monitored for mortality. Free light chain κ and λ levels were found to be elevated in CKD patients (especially in those on hemodialysis. Furthermore, FLC κ and λ levels were positively correlated with inflammation, aortic calcification and the levels of various uremic toxins levels. A multivariate linear regression analysis indicated that FLC κ and λ levels were independently associated with CKD stages and β2 microglobulin levels. Elevated FLC κ and λ levels appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score including age, CKD stage and aortic calcification. In conclusion, our results indicate that FLC κ and λ levels are elevated in CKD patients and are associated with inflammation, vascular calcification and levels of other uremic toxins. The observed link between elevated FLC levels and mortality appears to depend on other well-known factors.

  1. The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J.; Garte, S.J.

    1992-12-31

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.

  2. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review.

    Science.gov (United States)

    Moreno, Juan Antonio; Yuste, Claudia; Gutiérrez, Eduardo; Sevillano, Ángel M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Praga, Manuel; Egido, Jesús

    2016-04-01

    Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.

  3. Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation

    Directory of Open Access Journals (Sweden)

    Hui-Ju Lin

    2016-08-01

    Full Text Available Prevention and treatment of myopia is an important public problem worldwide. We found a higher incidence of myopia among patients with inflammatory diseases such as type 1 diabetes mellitus (7.9%, uveitis (3.7%, or systemic lupus erythematosus (3.5% compared to those without inflammatory diseases (p < 0.001 using data from children (<18 years old in the National Health Insurance Research database. We then examined the inhibition of myopia by atropine in Syrian hamsters with monocular form deprivation (MFD, an experimental myopia model. We found atropine downregulated inflammation in MFD eyes. The expression levels of c-Fos, nuclear factor κB (NFκB, interleukin (IL-6, and tumor necrosis factor (TNF-α were upregulated in myopic eyes and downregulated upon treatment with atropine. The relationship between the inflammatory response and myopia was investigated by treating MFD hamsters with the immunosuppressive agent cyclosporine A (CSA or the inflammatory stimulators lipopolysaccharide (LPS or peptidoglycan (PGN. Myopia progression was slowed by CSA application but was enhanced by LPS and PGN administration. The levels of c-Fos, NF-κB, IL-6, and TNF-α were upregulated in LPS- and PGN-treated eyes and downregulated by CSA treatment. These findings provide clinical and experimental evidence that inflammation plays a crucial role in the development of myopia.

  4. The investigation of electron-ion radiative and dielectronic recombination in high-temperature plasmas. Progress report for 1992--1993

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, V.L.

    1993-12-31

    This paper describes progress covered in the following six areas: (1) unified description of radiative and dielectronic recombination; (2) calculations of specific dielectronic satellite transitions; (3) Modeling of K{sub {alpha}} dielectronic satellite spectra; (4) effects of electron collisions and electric fields; (5) density-sensitive dielectronic satellite lines; and (6) polarization of atomic radiative emission in crossed electric and magnetic fields. Also discussed are proposed investigations and coordination with current tokamak observations.

  5. Progress on Updating the 1961-1990 National Solar Radiation Database: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Renne, D.; Wilcox, S.; Marion, B.; George, R.; Myers, D.; Stoffel, T.; Perez, R.; Stackhouse, P. Jr.

    2003-04-01

    The 1961-1990 National Solar Radiation Data Base (NSRDB) provides a 30-year climate summary and solar characterization of 239 locations throughout the United States. Over the past several years, the National Renewable Energy Laboratory (NREL) has received numerous inquiries from a range of constituents as to whether an update of the database to include the 1990s will be developed. However, there are formidable challenges to creating an update of the serially complete station-specific database for the 1971-2000 period. During the 1990s, the National Weather Service changed its observational procedures from a human-based to an automated system, resulting in the loss of important input variables to the model used to complete the 19611990 NSRDB. As a result, alternative techniques are required for an update that covers the 1990s. This paper examines several alternative approaches for creating this update and describes preliminary NREL plans for implementing the update.

  6. Progress on a Vlasov Treatment of Coherent Synchrotron Radiation from Arbitrary Planar Orbits

    CERN Document Server

    Bassi, Gabriele; Warnock, Robert L

    2005-01-01

    We study the influence of coherent synchrotron radiation (CSR) on particle bunches traveling on arbitrary planar orbits between parallel conducting plates (shielding). The time evolution of the phase space distribution is determined by solving the Vlasov-Maxwell equations in the time domain. This provides lower numerical noise than the macroparticle method, and allows the study of emittance degradation and microbunching in bunch compressors. We calculate the fields excited by the bunch in the lab frame using a formula simpler than that based on retarded potentials.* We have developed an algorithm for solving the Vlasov equation in the beam frame using arc length as the independent variable and our method of local characteristics (discretized Perron-Frobenius operator).We integrate in the interaction picture in the hope that we can adopt a fixed grid. The distribution function will be represented by B-splines, in a scheme preserving positivity and normalization of the distribution. The transformation between l...

  7. [Comparative evaluation of influence of low-intensity laser radiation of different spectrum components and regimen of laser work upon microcirculation in comprehensive treatment of chronic parodontitis].

    Science.gov (United States)

    Krechina, E K; Shidova, A V; Maslova, V V

    2008-01-01

    Comparative study of the influence details of low-intensity pulse and continuous oscillation of laser radiation of red and infrared parts of spectrum upon microcirculation indices in comprehensive treatment of chronic parodontitis of light and middle severity was performed. For the first time the predominantly activating influence upon microcirculation in gingival tissues of the pulsed laser radiation in the red part of spectrum was established.

  8. Eldor investigations of radiation processes. Annual progress report, 1977--1978

    Energy Technology Data Exchange (ETDEWEB)

    Kispert, L.D.

    1978-01-01

    Research is reported devoted to examining the role of the host matrix as a function of temperature in determining the type and yield of radicals produced by X-irradiation of a crystalline or glass material using electron-electron double resonance (ELDOR), electron-nuclear double resonance (ENDOR), electron spin resonance (ESR), and heavy atom substitution techniques. After many years of research on the effects of radiation on crystalline materials, it is still difficult to predict from the thermal history, nature of radiation, crystal structure or form of the parent molecule what radical species will be stable at any given temperature. However, an examination of the ELDOR spectra of an irradiated substance results in a partial or complete measure of the relaxation mechanisms which, in turn, are related to the host matrix itself. The host matrix can be charged slightly by using the heavy atom substitution technique, by using different methods of crystallization, and by including radical precursors in clathrates, permitting a study of the relation among host matrix variation, radical yield, and relaxation parameters. ESR investigations carried out on single crystals of irradiated fluoro, chloro, and bromo derivatives of acetamide and acetic acid have shown that a large matrix effect is present which is dependent upon the leaving group size, crystal structure and degree of crystallization. ELDOR measurements between 5/sup 0/K and 370/sup 0/K have shown a large variation in ELDOR intensity dependent on intramolecular motion, quadrupole coupling, p-orbital anisotropy, spin diffusion and tunnelling rotation. Forbidden esr lines overlapped by intense esr lines, esr lines too broad to detect, ENDOR transitions and radical cluster have been studied by ELDOR.

  9. Progress towards a more predictive model for hohlraum radiation drive and symmetry

    Science.gov (United States)

    Jones, O. S.; Suter, L. J.; Scott, H. A.; Barrios, M. A.; Farmer, W. A.; Hansen, S. B.; Liedahl, D. A.; Mauche, C. W.; Moore, A. S.; Rosen, M. D.; Salmonson, J. D.; Strozzi, D. J.; Thomas, C. A.; Turnbull, D. P.

    2017-05-01

    For several years, we have been calculating the radiation drive in laser-heated gold hohlraums using flux-limited heat transport with a limiter of 0.15, tabulated values of local thermodynamic equilibrium gold opacity, and an approximate model for not in a local thermodynamic equilibrium (NLTE) gold emissivity (DCA_2010). This model has been successful in predicting the radiation drive in vacuum hohlraums, but for gas-filled hohlraums used to drive capsule implosions, the model consistently predicts too much drive and capsule bang times earlier than measured. In this work, we introduce a new model that brings the calculated bang time into better agreement with the measured bang time. The new model employs (1) a numerical grid that is fully converged in space, energy, and time, (2) a modified approximate NLTE model that includes more physics and is in better agreement with more detailed offline emissivity models, and (3) a reduced flux limiter value of 0.03. We applied this model to gas-filled hohlraum experiments using high density carbon and plastic ablator capsules that had hohlraum He fill gas densities ranging from 0.06 to 1.6 mg/cc and hohlraum diameters of 5.75 or 6.72 mm. The new model predicts bang times to within ±100 ps for most experiments with low to intermediate fill densities (up to 0.85 mg/cc). This model predicts higher temperatures in the plasma than the old model and also predicts that at higher gas fill densities, a significant amount of inner beam laser energy escapes the hohlraum through the opposite laser entrance hole.

  10. Age-specific radiation dose commitment factors for a one-year chronic intake

    Energy Technology Data Exchange (ETDEWEB)

    Hoenes, G.R.; Soldat, J.K.

    1977-11-01

    During the licensing process for nuclear facilities, radiation doses and dose commitments must be calculated for people in the environs of a nuclear facility. These radiation doses are determined by examining characteristics of population groups, pathways to people, and radionuclides found in those pathways. The pertinent characteristics, which are important in the sense of contributing a significant portion of the total dose, must then be analyzed in depth. Dose factors are generally available for adults, see Reference 1 for example, however numerous improvements in data on decay schemes and half-lives have been made in recent years. In addition, it is advisable to define parameters for calculation of the radiation dose for ages other than adults since the population surrounding nuclear facilities will be composed of various age groups. Further, since infants, children, and teens may have higher rates of intake per unit body mass, it is conceivable that the maximally exposed individual may not be an adult. Thus, it was necessary to develop new radiation-dose commitment factors for various age groups. Dose commitment factors presented in this report have been calculated for a 50-year time period for four age groups.

  11. A porcine model of progressive Parkinson disease established by chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication

    DEFF Research Database (Denmark)

    Nielsen, M S; Glud, Andreas Nørgaard; Møller, Arne

    2009-01-01

    Parkinson disease (PD) is a common neurodegenerative disorder, resulting from a progressive dopaminergic neurons loss in the substantia nigra (SN). Attempts to discover effective compounds halting PD progression have so far failed in clinical trials, perhaps because current animal models do...... velocity for the intoxicated animals. This decrease could be reversed completely with apomorphine. For dosages of 2-12 mg MPTP/day, the symptoms failed to progress from the initial state of mild Parkinsonism, and some recovery was observed. Animals receiving 18 mg/day progressed to moderate parkinsonism...... analysis revealed steadily decreasing neuronal counts in the SN from 80,700 unilaterally in normal animals to 32,000, 27,000 and 18,000 at 12, 18 and 24 mg/day, respectively. We conclude that it is possible to induce progressive Parkinson disease based on chronic MPTP-intoxication in Göttingen minipigs...

  12. DNA damage caused by chronic transgenerational exposure to low dose gamma radiation in Medaka fish ( Oryzias latipes ).

    Science.gov (United States)

    Grygoryev, D; Moskalenko, O; Hinton, T G; Zimbrick, J D

    2013-09-01

    The effect of transgenerational exposure to low dose rate (2.4 and 21 mGy/day) gamma irradiation on the yield of DNA double-strand breaks and oxidized guanine (8-hydroxyguanine) has been studied in the muscle and liver tissue of a model organism, the Japanese medaka fish. We found the level of unrepaired 8-hydroxyguanine in muscle tissue increased nonlinearly over four generations and the pattern of this change depended on the radiation dose rate, suggesting that our treatment protocols initiated genomic instability and an adaptive response as the generations progressed. The yield of unrepaired double-strand breaks did not vary significantly among successive generations in muscle tissue in contrast to liver tissue in which it varied in a nonlinear manner. The 8-hydroxyguanine and DSB radiation yields were significantly higher at 2.4 mGy/day than at 21 mGy/day in both muscle and liver tissue in all generations. These data are consistent with the hypothesis of a threshold for radiation-induced activation of DNA repair systems below which tissue levels of DNA repair enzymes remain unchanged, leading to the accumulation of unrepaired damage at very low doses and dose rates.

  13. Value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection

    Directory of Open Access Journals (Sweden)

    BAO Teng

    2017-08-01

    Full Text Available ObjectiveTo investigate the clinical value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection. MethodsA retrospective analysis was performed for the clinical data of 1107 patients with different clinical stages of chronic HBV infection who had not received antiviral therapy at the time of hospitalization in The Second Affiliated Hospital of Anhui Medical University from May 2011 to December 2015, and according to the disease status, they were divided into HBeAg-positive chronic hepatitis B (CHB group, HBeAg-negative CHB group, compensated liver cirrhosis group (LC-C group, decompensated liver cirrhosis group (LC-D group, and primary liver cancer (PLC group. These groups were compared in terms of HBsAg expression and the association between HBsAg and clinical features. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between any two groups; the t-test was used for comparison of continuous data between two groups. The chi-square test was used for comparison of categorical data between these groups. Pearson correlation analysis was also performed. ResultsThere was a significant difference in serum HBsAg level between the HBeAg-positive CHB group, HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=100.45, P<0.001. The HBeAg-positive CHB group had significantly higher levels of HBsAg and HBV DNA than the HBeAg-negative CHB group (t= 16.67 an 16.22, both P<0.001. There were significant differences in HBsAg and HBV DNA levels between the HBeAg-positive CHB group, LC-C group, LC-D group, and PLC group (F= 42.92 and 27.38, both P<0.001, as well as between the HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=6.04 and 4.10, both P<0.05. HBV DNA level was significantly different across patients with different HBsAg levels (<1000 IU/ml, 1000-20 000 IU

  14. Maitake Mushroom Extracts Ameliorate Progressive Hypertension and Other Chronic Metabolic Perturbations in Aging Female Rats

    Directory of Open Access Journals (Sweden)

    Harry G. Preuss, Bobby Echard, Debasis Bagchi, Nicholas V. Perricone

    2010-01-01

    Full Text Available Objective: We assessed the ability of two commercially-available fractions labeled SX and D derived from the edible maitake mushroom to overcome many age-associated metabolic perturbations such as progressive, age-related elevation of blood pressure, over activity of the renin-angiotensin system (RAS, decreased insulin sensitivity, and inflammation in an in vivo laboratory model. Design and Method: We divided forty mature, female Sprague-Dawley rats (SD into five groups of eight. SD ingested regular rat chow containing added sucrose (20% w/w. The groups received baseline diet alone (control or baseline diet containing captopril, niacin-bound chromium, maitake fraction SX, or maitake fraction D. In addition to blood pressure readings, the following procedures were implemented: losartan and insulin challenges, evaluation of serum ACE activity, glucose tolerance testing, blood chemistries, LNAME challenge, and measurement of various circulating cytokines. Results: We found that implementation of all test conditions stopped the gradual elevation of systolic blood pressure (SBP in the SD over the four months of study, even reversing some of the previous elevation that occurred over time. In general, the treatment groups showed decreased activity of the RAS estimated by less lowering of SBP after losartan challenge and decreased serum ACE activity and were more sensitive to exogenous insulin challenge. TNFa levels decreased in all four test groups suggesting a lessening of the inflammatory state. Conclusions: We believe our data suggest that maitake mushroom fractions lessen age-related hypertension, at least in part, via effects on the RAS; enhance insulin sensitivity; and reduce some aspects of inflammation -- actions that should lead to a longer, healthier life span.

  15. ELDOR investigations of radiation processes. Annual progress report, 1980-1981

    Energy Technology Data Exchange (ETDEWEB)

    Kispert, L.D.

    1981-01-01

    Progress reports for this period are in the following areas of study: relaxation processes; and crystal field variation. Even though it is difficult to obtain accurate relaxation times from electrospin resonance (EPR) spectra they are needed for numerous experiments. Currently one of the best ways to obtain good T/sub 1//sub e/, T/sub 2//sub e/ and T/sub n/ values is from spin echo measurements. This past year, electron spin echo (ESE) measurements were again carried out at Argonne National Labs to deduce T/sub 1//sub e/, T/sub 2//sub e/ and spin exchange rates as a function of temperatures for several model compounds. More exact and complete data due to better data handling systems were obtained from two protons undergoing hopping rotation (CH/sub 2/COO/sup -/ in zinc acetate), for two methyl groups undergoing rotational exchange ((CH/sub 3/)/sub 2/CCOOH in ..cap alpha..-aminoisobutyric acid) and for two fluorine nuclei undergoing librational motion. So far, the temperature dependence of the ESE derived relaxation times show excellent agreement with the temperature dependence deduced from ELDOR measurements. Experiments involving the effect of variable wavelength uv light on the stability and reactivity of radicals in irradiated crystals has resulted in the identification of one photo induced process and the free radicals involved. However, the progress has been slow due to difficulties with the construction of key components of the equipment required. The effort to understand solid-state polymerization in considerable detail was expanded to the study of free radical induced solid-state polymerization by diffusing gaseous electron acceptors such as AsF/sub 5/, SbF/sub 5/ or SO/sub 3/ into various crystals/powders. The free radicals intermediates in thermally polymerized phenylacetylene were identified in an effort to examine thermally produced free radicals.

  16. Chronic non-progressive pneumonia of sheep in New Zealand - a review of the role of Mycoplasma ovipneumoniae.

    Science.gov (United States)

    Alley, M R; Ionas, G; Clarke, J K

    1999-10-01

    Chronic non-progressive pneumonia (CNP) is a common disease which affects lambs in New Zealand during late summer and autumn. Mycoplasma ovipneumoniae can be recovered from a high proportion of lesions but it is also present in some normal lungs. Bacteria, especially Pasteurella haemolytica, can also be recovered from more than half the lungs of affected animals. Isolates of M. ovipneumoniae are genetically heterogeneous, as demonstrated by examination of their DNA or total cellular proteins, and are serologically heterogeneous as shown by metabolic inhibition tests. The number of strains present in New Zealand is large and several distinguishable strains can be recovered from each affected lung. Mycoplasma ovipneumoniae has pathogenic potential as indicated by its ability to produce hydrogen peroxide, cause ciliostasis and by its possession of a capsule. Chronic non-progressive pneumonia can be transmitted consistently to over 50% of lambs by inoculation of pooled pneumonic lung homogenate and transmission can be suppressed by broad spectrum antibiotics. In contrast, penicillin does not prevent the development of lesions but diminishes their severity. Pooled lung homogenate treated with digitonin, which inactivates mycoplasmas, has failed to transmit CNP. Pure cultures of M. ovipneumoniae produce only mild lesions in some animals, whereas inoculation with pooled lung homogenate (from which no viruses were isolated) containing mixed strains of M. ovipneumoniae and free from bacteria, is more effective in producing lesions. Research work to date suggests that CNP may be initiated by colonisation of the lung by M. ovipneumoniae which causes ciliostasis and elicits an exudate allowing colonisation of the lungs by bacteria especially M. haemolytica and by other strains of M. ovipneumoniae. The immune response to the initial strain of M. ovipneumoniae may inhibit its replication but would be less effective in inhibiting heterologous strains of the organism allowing

  17. Progressive alterations of central nervous system structure and function are caused by charged particle radiation

    Science.gov (United States)

    Nelson, G. A.; Cns Nscor Team

    A new NASA-sponsored program project (NSCOR) has been organized to conduct the first comprehensive investigation of the response of a mammalian brain structure (mouse hippocampus) to charged-particle radiation. The NSCOR collaboration has three main goals. The first goal is to quantify the time- and dose-dependent changes in cellular composition and architecture. By using stereology on preserved brains, subsets of cells (neurons, glia, endothelia and stem cells) will be quantified out to 2 years after irradiation with accelerated protons and iron ions. To further characterize changes in vasculature architecture a polymer infusion technique will be used to produce a three-dimensional vasculature cast that then will be mapped by x-ray tomography to determine topological changes, and microscopic infarcts associated with amyloid protein deposits. The 2nd goal is to quantify hippocampal function(s). The primary measurement of function will be extracellular electrical recordings from hippocampal ``brain slices'' that reflect underlying functions such as connectivity, action potential generation & conduction, and neurotransmitter formation, secretion, and uptake. Individual nerve membrane properties will be assessed by ``patch clamp'' recordings. Two non-invasive methods will evaluate brain function and the evolution of changes with time. Electroencephalograms will map macroscopic spontaneous electrical activity while two state-of-the-art MRI magnetization sequences will visualize and quantify local oxygen utilization and white matter fiber tracts structural integrity. To quantify the brains' overall performance under stress, animals will receive a systemic shock mediated by the immune system in the form of a reaction to lipopolysaccharide. A second strategy will employ the APP23 transgenic mouse that develops the pathological changes associated with Alzheimer's disease. Measurements of irradiated mice will determine whether radiation exposure affects the latency and

  18. Over-expression of heme oxygenase-1 in peripheral blood predicts the progression and relapse risk of chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    Wei Sixi; Wang Yating; Chai Qixiang; Fang Qin; Zhang Yaming; Lu Yinghao; Wang Jishi

    2014-01-01

    Background There are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML).Heme oxygenase-1 (HO-1),as one of the most important oxidation-regulating enzymes in vivo,suggests the onset and progression of cancer when highly expressed.Furthermore,HO-1 level is related with the occurrence and development of hematological diseases.But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto.This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.Methods A total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR.Routine blood test was performed to detect the changes of leukocyte and platelet counts.The proportion of primitive cells in BM was detected by flow cytometry.The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis.The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.Results Relative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P <0.0001),which were 0.57±3.78 and (1.417±1.125)×10-6,respectively.HO-1 expression level in CML patients was 0.061 5±0.062 4,which decreased to 0.009 4±0.006 7 upon CMoR,and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)× 10-6,P <0.001.When relapse occurred,HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse.According to progression of CML,HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7± 0.447 0).And there was a linear correlation between HO-1 expression

  19. Coexpression network analysis in chronic hepatitis B and C hepatic lesions reveals distinct patterns of disease progression to hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Danning He; Zhi-Ping Liu; Masao Honda; Shuichi Kaneko; Luonan Chen

    2012-01-01

    Chronic infections with the hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risks of hepatocellular carcinoma (HCC),and great efforts have been made towards the understanding of the different mechanisms that link the viral infection of hepatic lesions to HCC development.In this work,we developed a novel framework to identify distinct patterns of gene coexpression networks and inflammation-related modules from genome-scale microarray data upon viral infection,and further classified them into oncogenic and dysfunctional ones.The core of our framework lies in the comparative study on viral infection modules across different disease stages and disease types--the module preservation during disease progression is evaluated according to the change of network connectivity in different stages,while the similarity and difference in HBV and HCV are evaluated by comparing the overlap of gene compositions and functional annotations in HBV and HCV modules.In particular,we revealed two types of driving modules related to infection for carcinogenesis in HBV and HCV,respectively,i.e.pro-apoptosis modules that are oncogenic in HBV,and antiapoptosis and inflammation modules that are oncogenic in HCV,which are in concordance with the results of previous differential expression-based approaches.Moreover,we found that intracellular protein transmembrane transportation and the transmembrane receptor protein tyrosine kinase signaling pathway act as oncogenic factors in HBV-HCC.Our findings provide novel insights into viral hepatocarcinogenesis and disease progression,and also demonstrate the advantages of an integrative and comparative network analysis over the existing differential expression-based approach and virus-host interactome-based approach.

  20. Interaction of radiation with matter. Research progress report, November 1, 1979-October 31, 1980

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-09-01

    The mechanisms of dissipation of energy in organic and inorganic materials, and the application of the technique developed to a study of selected problems of environmental concern in the production of energy from fossil fuels were studied. In the Inorganic Phase of the work the research involves (1) measurements of cross-sections for K and L-shell ionization processes for heavy projectiles in the low velocity region, (2) experimental tests of target dependence of the effective-charge theory for light projectiles, (3) theoretical studies on the energy loss of swift particles in plasmas over a broad density and temperature range. The organic phase of the work falls into a series of closely related areas, all derived from a study of the interaction of radiation with matter. (1) New techniques for the study of small particulates (approx. 1..mu..); composition, mass (to +-1 pg) and charge (+-1 electron) can be determined. (2) External photoelectric effects as a tool in arriving at the electronic structure of organic crystals. (3) The interaction of water with charge carriers in organic crystals, producing reactive chemical species, such as Oh and HSO/sub 3/ radicals. (4) Mechanisms of interaction of air-pollutant polycyclic aromatic carcinogens with DNA and the study of the conformation of the adducts.

  1. ONERA's progress in modelling and specifying the Earth's radiation belts dynamics

    Science.gov (United States)

    Maget, Vincent; Bourdarie, Sebastien; Boscher, Daniel; Lazaro, Didier; Sicard-Piet, Angelica; Grimald, Sandrine Rochel

    In the recent years, ONERA has been involved in two complementary FP7 projects: SPACECAST and MAARBLE projects. Thanks to these European grants, and to the continuous support of CNES (CRATERRE project), many improvements have been conducted in: 1) modelling the processes driving the radiation belts (boundary conditions, radial diffusion, wave-particle interactions, drop-outs modelling), 2) data analysis and, 3) data assimilation. This talk aims at presenting these improvements as well as the remaining weaknesses with comparison with recent data sets such as the Van Allen Probes observations. We will highlight what are the upcoming challenges according to us and what are the key directions to continue exploring in order to improve current specification models. SPACECAST and MAARBLE have received fundings from the European Community’s Seventh Framework Programme (FP7-SPACE-.2010-1, SP1 Cooperation, Collaborative project) under grant agreement n262468 and n284520 respectively. This paper reflects only the authors’ views and the European Union is not liable for any use that may be made of the information contained therein. The CRATERRE project has received fundings from CNES.

  2. Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

    Science.gov (United States)

    Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

    2014-01-01

    Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

  3. Acoustic Radiation Force Impulse Elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Sporea, Ioan, E-mail: isporea@umft.ro [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Bota, Simona, E-mail: bota_simona1982@yahoo.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Peck-Radosavljevic, Markus, E-mail: markus.peck@meduniwien.ac.at [Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Sirli, Roxana, E-mail: roxanasirli@gmail.com [Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Timisoara (Romania); Tanaka, Hironori, E-mail: hironori@hyo-med.ac.jp [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Iijima, Hiroko, E-mail: hiroko.iijima@nifty.com [Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Badea, Radu, E-mail: rbadea2003@yahoo.com [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Lupsor, Monica, E-mail: monica.lupsor@umfcluj.ro [3rd Medical Clinic, University of Medicine, Cluj Napoca (Romania); Fierbinteanu-Braticevici, Carmen, E-mail: cfierbinteanu@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Petrisor, Ana, E-mail: ana1petrisor@yahoo.com [2nd Medical Clinic and Gastroenterology, University Hospital, Bucharest (Romania); Saito, Hidetsugu, E-mail: hidetsugusaito@gmail.com [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Ebinuma, Hirotoshi, E-mail: ebinuma@a5.keio.jp [Department of Internal Medicine, School of Medicine, Keio University, Tokyo (Japan); Friedrich-Rust, Mireen, E-mail: Mireen.Friedrich-Rust@kgu.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); Sarrazin, Christoph, E-mail: sarrazin@em.uni-frankfurt.de [Department of Internal Medicine, J.W. Goethe University, Frankfurt/Main (Germany); and others

    2012-12-15

    Aim: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C. Patients and methods: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5–10 valid measurements, expressed in meters/second – m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6–10 valid measurements, expressed in kiloPascals – kPa). Results: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r = 0.654) was found between ARFI measurements and fibrosis (p < 0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 – cut-off > 1.19 m/s (AUROC = 0.779), F ≥ 2 – cut-off > 1.33 m/s (AUROC = 0.792), F ≥ 3 – cut-off > 1.43 m/s (AUROC = 0.829), F = 4 – cut-off > 1.55 m/s (AUROC = 0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r = 0.728 vs. 0.689, p = 0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p = 0.01) and fibrosis (F ≥ 1, METAVIR) (p = 0.01). Conclusion: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients.

  4. Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.

    Directory of Open Access Journals (Sweden)

    Martin Wagner

    Full Text Available Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD. It may be explained by reduced erythropoietin (EPO synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD, were enrolled (2003-2005, if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine were analyzed by Cox proportional hazards models.Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7% and forty (16.1% patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05. Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05. Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05.We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the

  5. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

    Directory of Open Access Journals (Sweden)

    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  6. The relation of serum myeloperoxidase to disease progression and mortality in patients with chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Park, Hye Yun; Man, S F Paul; Tashkin, Donald; Wise, Robert A; Connett, John E; Anthonisen, Nicholas A; Sin, Don D

    2013-01-01

    Myeloperoxidase is a strong oxidant stored in primary granules of neutrophils with potent antibacterial and proatherogenic properties. Myeloperoxidase has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship of myeloperoxidase to health outcomes in COPD is not well known. We measured serum myeloperoxidase levels from 4,677 subjects with mild to moderate airflow limitation in the Lung Health Study. Using a Cox proportional hazards model, we determined the relationship of serum myeloperoxidase concentration to the risk of all-cause and disease specific causes of mortality. We found that serum myeloperoxidase concentrations were significantly related to accelerated decline in forced expiratory volume in 1 second (FEV1) over 11 years of follow-up (pmyeloperoxidase concentrations were also associated with increased risk of cardiovascular mortality (p = 0.036). Individuals in the highest quintile of myeloperoxidase had a hazard ratio of cardiovascular mortality of 1.90 (95% confidence interval 1.00-3.58; p = 0.049) compared with those in the lowest quintile, which was particularly notable in patients who continued to smoke (adjusted p-value of 0.0396). However, serum myeloperoxidase concentration was not related to total mortality, respiratory mortality, or deaths from malignancies. In conclusion, increased serum myeloperoxidase levels are associated with rapid lung function decline and poor cardiovascular outcomes in COPD patients, which support the emerging role of myeloperoxidase in the pathogenesis of COPD progression and cardiovascular disease.

  7. Sinorhizobium meliloti CpdR1 is critical for co-ordinating cell cycle progression and the symbiotic chronic infection.

    Science.gov (United States)

    Kobayashi, Hajime; De Nisco, Nicole J; Chien, Peter; Simmons, Lyle A; Walker, Graham C

    2009-08-01

    ATP-driven proteolysis plays a major role in regulating the bacterial cell cycle, development and stress responses. In the nitro -fixing symbiosis with host plants, Sinorhizobium meliloti undergoes a profound cellular differentiation, including endoreduplication of the ome. The regulatory mechanisms governing the alterations of the S. meliloti cell cycle in planta are largely unknown. Here, we report the characterization of two cpdR homologues, cpdR1 and cpdR2, of S. meliloti that encode single-domain response regulators. In Caulobacter crescentus, CpdR controls the polar localization of the ClpXP protease, thereby mediating the regulated proteolysis of key protein(s), such as CtrA, involved in cell cycle progression. The S. meliloti cpdR1-null mutant can invade the host cytoplasm, however, the intracellular bacteria are unable to differentiate into bacteroids. We show that S. meliloti CpdR1 has a polar localization pattern and a role in ClpX positioning similar to C. crescentus CpdR, suggesting a conserved function of CpdR proteins among alpha-proteobacteria. However, in S. meliloti, free-living cells of the cpdR1-null mutant show a striking morphology of irregular coccoids and aberrant DNA replication. Thus, we demonstrate that CpdR1 mediates the co-ordination of cell cycle events, which are critical for both the free-living cell division and the differentiation required for the chronic intracellular infection.

  8. Progress in the treatment of elderly/unfit chronic lymphocytic leukemia patients: results of the German CLL-11 trial.

    Science.gov (United States)

    Molica, Stefano

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia and affects mostly the elderly. Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab is generally considered a standard treatment for younger fit patients with CLL. In a recent randomized Phase III study of patients with newly diagnosed CLL and coexisting conditions, obinutuzumab, a humanized anti-CD20 glycoengineered type 2 antibody, used in combination with chlorambucil, demonstrated significant improvement in progression-free survival and several other outcome parameters, in comparison to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Results of this trial clearly established that obinutuzumab in combination with chlorambucil represent the new first-line standard of treatment in this setting. A broad range of novel agents with different mechanisms of action have already proven their efficacy in CLL. New drugs targeting specific molecular features, such as ibrutinib, idelalisib or ABT-199, are being tested at present, and their advent is very likely to change the future treatment paradigm of CLL that relies today on chemoimmunotherapy for both fit and elderly/unfit patients.

  9. Comparison of qualitative and quantitative analysis of T2-weighted MRI scans in chronic-progressive multiple sclerosis

    Science.gov (United States)

    Adams, Hans-Peter; Wagner, Simone; Koziol, James A.

    1998-06-01

    Magnetic resonance imaging (MRI) is routinely used for the diagnosis of multiple sclerosis (MS), and for objective assessment of the extent of disease as a marker of treatment efficacy in MS clinical trials. The purpose of this study is to compare the evaluation of T2-weighted MRI scans in MS patients using a semi-automated quantitative technique with an independent assessment by a neurologist. Baseline, 6- month, and 12-month T2-weighted MRI scans from 41 chronic progressive MS patients were examined. The lesion volume ranged from 0.50 to 51.56 cm2 (mean: 8.08 cm2). Reproducibility of the quantitative technique was assessed by the re-evaluation of a random subset of 20 scans, the coefficient of variation of the replicate determinations was 8.2%. The reproducibility of the neurologist evaluations was assessed by the re-evaluation of a random subset of 10 patients. The rank correlation between the results of the two methods was 0.097, which did not significantly differ from zero. Disease-related activity in T2-weighted MRI scans is a multi-dimensional construct, and is not adequately summarized solely by determination of lesion volume. In this setting, image analysis software should not only support storage and retrieval as sets of pixels, but should also support links to an anatomical dictionary.

  10. Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

    Science.gov (United States)

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan

    2014-10-17

    This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

  11. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

    Science.gov (United States)

    Yentrapalli, Ramesh; Azimzadeh, Omid; Sriharshan, Arundhathi; Malinowsky, Katharina; Merl, Juliane; Wojcik, Andrzej; Harms-Ringdahl, Mats; Atkinson, Michael J; Becker, Karl-Friedrich; Haghdoost, Siamak; Tapio, Soile

    2013-01-01

    The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.

  12. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

    Directory of Open Access Journals (Sweden)

    Ramesh Yentrapalli

    Full Text Available The etiology of radiation-induced cardiovascular disease (CVD after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h causes human umbilical vein endothelial cells (HUVECs to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.

  13. Do diagnostic segmental nerve root blocks in chronic Dow back pain patients with radiation to the leg lack distinct sensory effects? A preliminary study

    NARCIS (Netherlands)

    Wolff, AP; Groen, G J; Wilder-Smith, O H G; Richardson, J; van Egmond, J; Crul, B J P

    2006-01-01

    Background. The present preliminary study documents the effects of a selective nerve root block (SNB) with short or long acting local anaesthetic compared with baseline measurements in patients with chronic low back pain radiating to the leg with maximum pain in one dermatome (1-4). Methods. Ten con

  14. Biochemical Changes in Saliva of Patients with Chronic Generalized Parodontitis under Combined Action of Alternating Running Magnetic Field and Laser Radiation

    Directory of Open Access Journals (Sweden)

    O.Yu. Guseva

    2009-09-01

    Full Text Available Biochemical changes in oral fluid of patients with chronic generalized parodontitis were investigated; the most informative indices were found out, they were used for estimating complex therapy effectiveness by means of low intensive helium — neon laser radiation and alternating running magnetic field

  15. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

  16. Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

    Science.gov (United States)

    Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

    2017-04-03

    BCR-ABL kinase domain (KD) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-KD mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-KD. Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-KD mutation screening in late chronic phase CML patients for improved clinical management of disease.

  17. Cutaneous changes in rats induced by chronic skin exposure to ultraviolet radiation and organophosphate pesticide.

    Science.gov (United States)

    Fernandes, Tania Rita Moreno de Oliveira; Santos, Itamar; Korinsfky, Juliana Pedrosa; Lima e Silva, Benedyto Sávio; Carvalho, Luis Otávio; Plapler, Hélio

    2014-01-01

    To study the possible potentiation of the carcinogenic effects of ultraviolet radiation associated with an organophosphate pesticide. Forty Wistar rats were assigned into four groups (n=10 each) randomized according to the procedures: group A received only UVR-B radiation; group B, UVR-B for eight weeks followed by a seven week period of pesticide exposure; group C, UVR-B + pesticide concomitantly: group D, only pesticide application. At the end of the fifth, tenth and fifteenth weeks the animals were photographed. Skin biopsy and histopathological study with Hematoxylin-Eosin were done on the fifteenth week. Statistical analysis with Fisher's and Sign (unilateral) tests, 5% value for significance. Macroscopic lesions in the group A evolved from the erythema to erythema + desquamation. The groups B and C, with the association of two carcinogens, and group D presented evolution to keratosis, with higher incidence in group D. The histology showed a significant increase in the severity of injuries when the UVR-B and the pesticide were applied simultaneously, leading to cellular atypia. Concurrent association of UVR-B to organophosphate pesticide produced more severe lesions microscopically, although this has not been so apparent macroscopically. In daily practice the clinical evaluation should be complemented with laboratory evaluation.

  18. Impact of chronic, low-level ionising radiation exposure on terrestrial invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Hingston, J.; Wood, M.D.; Copplestone, D.; Zinger, I. [Liverpool Univ., School of Biological Sciences, Merseyside (United Kingdom)

    2004-07-01

    There is a need to confirm that the environment is being adequately protected from the mixture of contaminants released into it. In the field of environmental radioactivity, tools have been developed to assess the impacts of ionising radiation on wildlife. The scientific data upon which these assessments are based is, however, lacking. New documentation has been produced by the UK Environment Agency to provide guidelines on structuring experiments (using environmentally relevant doses) and select suitable non-human species and endpoints for study. It is anticipated that this documentation will be used to direct future experiments in this field. This paper presents the results of the first of these experiments. Numbers of the earthworm Eisenia fetida and the wood louse Porcellio scaber were segregated and constantly exposed to one of six radiation doses (background, 0.1, 0.4, 1.5, 4.0 and 8.0 mGyh{sup -1}) for a total of 16 and 14 weeks respectively. The endpoints of mortality, number of viable offspring and average weight of an individual were recorded and the results of this study will be discussed here. (author)

  19. Do frequent moderate exacerbations contribute to progression of chronic obstructive pulmonary disease in patients who are ex-smokers?

    Science.gov (United States)

    Dreyse, Jorge; Díaz, Orlando; Repetto, Paula B; Morales, Arturo; Saldías, Fernando; Lisboa, Carmen

    2015-01-01

    Background In addition to smoking, acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease (COPD). However, these findings come from studies including active smokers, while results in ex-smokers are scarce and contradictory. The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second (FEV1) and impairment of functional and clinical outcomes in ex-smoking COPD patients. Methods A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition. Evaluation included anthropometry, spirometry, inspiratory capacity, peripheral capillary oxygen saturation, severity of dyspnea, a 6-minute walking test, BODE (Body mass index, airflow Obstruction, Dyspnea, Exercise performance) index, and quality of life (St George’s Respiratory Questionnaire and Chronic Respiratory Disease Questionnaire). Severity of exacerbation was graded as moderate or severe according to health care utilization. Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year. Random effects modeling, within hierarchical linear modeling, was used for analysis. Results During follow-up, 419 (96% moderate) acute exacerbations were registered. At baseline, frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index, and also showed greater impairment in inspiratory capacity, forced vital capacity, peripheral capillary oxygen saturation, 6-minute walking test, and quality of life. However, no significant difference in FEV1 decline over time was found between the two groups (54.7±13 mL/year versus 85.4±15.9 mL/year in frequent exacerbators and infrequent exacerbators, respectively

  20. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, P.R. Vivek, E-mail: prvkumar06@gmail.com [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Seshadri, M. [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Jaikrishan, G. [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Das, Birajalaxmi [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2015-05-15

    Highlights: • Effect of chronic low dose natural radiation in radio adaptive response studied. • PBMCs of subjects from NLNRA and HLNRA were challenged with gamma radiation. • DNA damage and repair in PBMCs was compared using the alkaline comet assay. • Significant reduction in DNA damage in subjects of high dose group from HLNRA noted. • Probable induction of an in vivo radio adaptive response in subjects from HLNRA. - Abstract: This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year{sup −1}), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N = 43, range 1.07 mSv year{sup −1} to 5.55 mSv year{sup −1}) and 9.62 mSv (N = 34, range 6.07 mSv year{sup −1} to17.41 mSv year{sup −1}), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P = 0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from

  1. Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

    Science.gov (United States)

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2011-07-01

    nuclear workers, which should improve knowledge about the risks associated with chronic low doses and provide useful risk estimates for radiation protection.

  2. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, E.M.

    1984-01-01

    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed.

  3. Analyses of critical target cell responses during preclinical phases of evolving chronic radiation-induced myeloproliferative disease-exploitation of a unique canine model

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.; Frazier, M.E.

    1988-01-01

    This document briefly summarizes and highlights ongoing studies on the cellular and molecular processes involved in the induction and progression of myeloid leukemia in dogs chronically exposed to low daily doses of wholebody gamma irradiation. Under such conditions, select groups of dogs exhibit extremely high frequencies of myeloproliferative disease (MPD) (i.e., /congruent/50%) of which myeloid leukemia is most prominent. 2 figs.

  4. Analyses of critical target cell responses during preclinical phases of evolving chronic radiation-induced myeloproliferative disease-exploitation of a unique canine model

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.; Frazier, M.E.

    1988-01-01

    This document briefly summarizes and highlights ongoing studies on the cellular and molecular processes involved in the induction and progression of myeloid leukemia in dogs chronically exposed to low daily doses of wholebody gamma irradiation. Under such conditions, select groups of dogs exhibit extremely high frequencies of myeloproliferative disease (MPD) (i.e., /congruent/50%) of which myeloid leukemia is most prominent. 2 figs.

  5. The role of serum biomarkers in predicting fibrosis progression in pediatric and adult hepatitis C virus chronic infection.

    Directory of Open Access Journals (Sweden)

    Pamela Valva

    Full Text Available BACKGROUND/AIMS: Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection. METHODS: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1, hyaluronic acid (HA and aminoterminal peptide of procollagen type III (PIIINP were tested. RESULTS: Significant fibrosis (F≥2 and advanced fibrosis (F≥3 represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011 and PIIINP (p = 0.016 were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039 just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022 in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598-0.932. In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736-0.994, 0.894 (IC95% 0.689-0.984 and 0.835 (IC95% 0.617-0.957], respectively. In children, according to the cut off (165.7 ng/mL value for TIMP-1, biopsies could have been avoided in 72% (18/25. Considering the cut off for HA (109.7 ng/mL, PIIINP (9.1 µg/L, and TGF-ß1 (10,848.3 pg/mL, biopsies could have been avoided in 87% (19/22 of adult patients by using HA and 73% (16/22 using PIIINP or TGF-ß1. CONCLUSIONS: In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.

  6. 几种常用橡胶的辐射交联研究进展%Research Progress of Radiation Crosslinking of Rubber

    Institute of Scientific and Technical Information of China (English)

    丁曼; 张本尚; 杨艳平; 刘磊; 李佰发

    2013-01-01

    In this paper, the research progress of radiation crosslinking of rubber is presented. The radiation crosslinking of NR, IR, IIR, SBR and EPDM et al. is introduced, and the inlfuence of molecular structure, radiation temperature and radiation dosage on the crosslinking efifciency are analyzed.%介绍天然橡胶、聚异戊二烯橡胶、聚丁二烯橡胶、丁苯橡胶和三元乙丙橡胶等常用橡胶的辐射交联研究进展,分析分子结构、辐射温度及辐射剂量等因素对橡胶辐射交联效应的影响。

  7. 有机硅材料辐射加工技术进展%Progress on Radiation Processing Technology of Silicone Materials

    Institute of Scientific and Technical Information of China (English)

    周成飞

    2014-01-01

    The research progress of radiation modification on the silicone materials was summarized .The radiation crosslinking and radiation grafting technique in application of silicone materials were discussed .The current research trend on preparation of POSS-polymer composites was also introduced .Finally, the develop-ment of preparation of SiC materials by radiation technology was introduced .%综述了有机硅材料辐射改性的研究进展。主要评述了辐射交联和辐射接枝技术在有机硅材料改性中的应用情况;介绍了辐射法制备POSS-聚合物复合材料的研究及SiC材料辐射制备技术的发展现状。

  8. Progression of retinal ganglion cell loss in multiple sclerosis is associated with new lesions in the optic radiations.

    Science.gov (United States)

    Klistorner, A; Graham, E C; Yiannikas, C; Barnett, M; Parratt, J; Garrick, R; Wang, C; You, Y; Graham, S L

    2017-08-10

    The mechanism of retinal ganglion cell and retinal nerve fiber layer loss in multiple sclerosis (MS) remains unknown. This study aimed to investigate the association between temporal retinal nerve fiber layer (tRNFL) thinning and disease activity in the brain determined by T2 lesions on magnetic resonance imaging (MRI). Fifty-five consecutive patients with relapsing-remitting MS and 25 controls were enrolled. All patients underwent annual optical coherence tomography and high-resolution MRI scans for tRNFL thickness and brain lesion volume analysis, respectively. Significant tRNFL thickness reduction was observed over the 3-year follow-up period at a relatively constant rate (1.02 μm/year). Thinning of tRNFL fibers was more prominent in younger patients (P = 0.01). The tRNFL loss was associated with new MRI lesions in the optic radiations (ORs). There was significantly greater tRNFL thinning in patients with new lesional activity in the ORs compared with patients with new lesions outside the ORs (P = 0.009). This study supports the notion that retrograde transneuronal degeneration caused by OR lesions might play a role in progressive retinal nerve fiber layer loss. In addition, the results of the study also indicate that the disease-related neurodegenerative changes in the retina start much earlier than the clinical diagnosis of MS. © 2017 EAN.

  9. Modeling deterministic effects in hematopoietic system caused by chronic exposure to ionizing radiation in large human cohorts.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2010-09-01

    A new model of the hematopoietic system for humans chronically exposed to ionizing radiation allows for quantitative description of the initial hematopoiesis inhibition and subsequent increase in the risks of late stochastic effects such as leukemia. This model describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the three blood cell types (leukocytes, erythrocytes, and platelets). The model parameters are estimated from the results of other experiments. They include the steady-state numbers of hematopoietic stem cells and peripheral blood cell lines for an unexposed organism, amplification parameters for each blood cell line, parameters describing the proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity in respect to cell death and non-lethal cell damages. The dynamic model of hematopoiesis is applied to the data on a subcohort of the Techa River residents with hematological measurements (e.g., blood counts) performed in 1950-1956 (which totals to about 3,500 exposed individuals). Among well-described effects observed in these data are the slope values of the dose-effect curves describing the hematopoietic inhibition and the dose rate patterns of the fractions of cytopenic states (e.g., leukopenia, thrombocytopenia). The model has been further generalized by inclusion of the component describing the risk of late stochastic effects. The risks of the development of late effects (such as leukemia) in population groups with specific patterns of early reactions in hematopoiesis (such as leukopenia induced by ionizing radiation) are investigated using simulation studies and compared to data.

  10. Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

    Science.gov (United States)

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2012-11-01

    Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

  11. Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression.

    Science.gov (United States)

    Hsu, Chi-Yuan; Xie, Dawei; Waikar, Sushrut S; Bonventre, Joseph V; Zhang, Xiaoming; Sabbisetti, Venkata; Mifflin, Theodore E; Coresh, Josef; Diamantidis, Clarissa J; He, Jiang; Lora, Claudia M; Miller, Edgar R; Nelson, Robert G; Ojo, Akinlolu O; Rahman, Mahboob; Schelling, Jeffrey R; Wilson, Francis P; Kimmel, Paul L; Feldman, Harold I; Vasan, Ramachandran S; Liu, Kathleen D

    2017-01-01

    Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers. Copyright © 2016 International Society of Nephrology. All rights reserved.

  12. Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

    Science.gov (United States)

    Senevirathna, Lalantha; Abeysekera, Tilak; Nanayakkara, Shanika; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Harada, Kouji H; Hitomi, Toshiaki; Komiya, Toshiyuki; Muso, Eri; Koizumi, Akio

    2012-05-01

    The alarming rise in the prevalence of chronic kidney disease of uncertain etiology (CKDu) among the low socioeconomic farming community in the North Central Province of Sri Lanka has been recognized as an emerging public health issue in the country. This study sought to determine the possible factors associated with the progression and mortality of CKDu. The study utilized a single-center cohort registered in 2003 and followed up until 2009 in a regional clinic in the endemic region, and used a Cox proportional hazards model. We repeatedly found an association between disease progression and hypertension. Men were at higher risk of CKDu than women. A significant proportion of the patients in this cohort were underweight, which emphasized the need for future studies on the nutritional status of these patients. Compared with findings in western countries and other regions of Asia, we identified hypertension as a major risk factor for progression of CKDu in this cohort.

  13. Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer

    Science.gov (United States)

    Ohtani, Masahiro; Suto, Hiroyuki; Nosaka, Takuto; Saito, Yasushi; Ozaki, Yoshihiko; Hayama, Ryoko; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Hiramatsu, Katsushi; Nemoto, Tomoyuki; Shioura, Hiroki; Kimura, Hirohiko; Aoki, Yoshitaka; Yokoyama, Osamu; Nakamoto, Yasunari

    2016-01-01

    Background. Chronic radiation proctopathy (CRP) is late toxicity and associated with morbidity. Aim. To investigate the predictors of prognosis in patients with CRP after brachytherapy (BT). Methods. One hundred four patients with prostate cancer were treated with BT or BT followed by external-beam radiotherapy (BT + EBRT). We retrospectively investigated the 5-year incidence of rectal bleeding and endoscopic findings of CRP using the Vienna Rectoscopy Score (VRS). Twenty patients with VRS ≥ 1 were divided into the improved VRS group without treatment, unchanged VRS group, and treated group. The parameters associated with alteration of VRS were analyzed. Results. The incidence of rectal bleeding was 24%. The risk of rectal bleeding was higher in patients treated with BT + EBRT compared to those treated with BT (p 1 cm2 was higher in the treated group than in both the improved and unchanged VRS groups (p < 0.05). Conclusions. Patients treated with BT + EBRT have a high risk of CRP. Endoscopic findings were useful for prognostic prediction of CRP. PMID:27378828

  14. Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Masahiro Ohtani

    2016-01-01

    Full Text Available Background. Chronic radiation proctopathy (CRP is late toxicity and associated with morbidity. Aim. To investigate the predictors of prognosis in patients with CRP after brachytherapy (BT. Methods. One hundred four patients with prostate cancer were treated with BT or BT followed by external-beam radiotherapy (BT + EBRT. We retrospectively investigated the 5-year incidence of rectal bleeding and endoscopic findings of CRP using the Vienna Rectoscopy Score (VRS. Twenty patients with VRS ≥ 1 were divided into the improved VRS group without treatment, unchanged VRS group, and treated group. The parameters associated with alteration of VRS were analyzed. Results. The incidence of rectal bleeding was 24%. The risk of rectal bleeding was higher in patients treated with BT + EBRT compared to those treated with BT (p 1 cm2 was higher in the treated group than in both the improved and unchanged VRS groups (p<0.05. Conclusions. Patients treated with BT + EBRT have a high risk of CRP. Endoscopic findings were useful for prognostic prediction of CRP.

  15. Long-term persistent GBV-B infection and development of a chronic and progressive hepatitis C-like disease in marmosets

    Directory of Open Access Journals (Sweden)

    Yuki eIwasaki

    2011-12-01

    Full Text Available It has been shown that infection of GB virus B (GBV-B, which is closely related to HCV, develop acute self-resolving hepatitis in tamarins. In this study we sought to examine longitudinally the dynamics of viral and immunological status following GBV-B infection of marmosets and tamarins. Surprisingly, two of four marmosets but not tamarins experimentally challenged with GBV-B developed long-term chronic infection with fluctuated viremia, recurrent increase of alanine aminotransferase and plateaued titers of the anti-viral antibodies, which was comparable to chronic hepatitis C in humans. Moreover, one of the chronically infected marmosets developed an acute exacerbation of chronic hepatitis as revealed by biochemical, histological and immunopathological analyses. Of note, periodical analyses of the viral genomes in these marmosets indicated frequent and selective nonsynonymus mutations, suggesting efficient evasion of the virus from anti-viral immune pressure. These results demonstrated for the first time that GBV-B could induce chronic hepatitis C-like disease in marmosets and that the outcome of the viral infection and disease progression may depend on the differences between species and individuals.

  16. Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US

    Directory of Open Access Journals (Sweden)

    Adams EH

    2016-06-01

    Full Text Available Edgar H Adams,1 Heather J McElroy,2 Margarita Udall,3 Elizabeth T Masters,3 Rachael M Mann,4 Caroline P Schaefer,1 Joseph C Cappelleri,5 Andrew G Clair,3 Markay Hopps,3 Shoshana R Daniel,6 Philip Mease,7,8 Stuart L Silverman,9,10 Roland Staud11 1Covance Market Access Services Inc, Gaithersburg, MD, USA; 2Covance (Asia Pte Ltd, Singapore, Singapore; 3Pfizer Inc, New York, NY, 4Covance Market Access Services Inc, San Diego, CA, 5Pfizer Inc, Groton, CT, 6Covance Market Access Services Inc, Conshohocken, PA, 7Division of Rheumatology Research, Swedish Medical Center, Seattle, WA, 8Department of Rheumatology, University of Washington, Seattle, WA, 9Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, 10Department of Medicine, University of California, Los Angeles, CA,11Department of Medicine, University of Florida, Gainesville, FL, USA Background: A previous fibromyalgia (FM research reports that 20%–47% of diagnosed patients may not meet the study definition of FM 1–2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. Methods: This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP diagnosis stability over time. At enrollment (baseline, subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months, visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM, FM-CWP+ (screened positive for CWP but did not receive physician diagnosis of FM, and FM-CWP- (screened negative

  17. Microvesicles as a Biomarker for Tumor Progression versus Treatment Effect in Radiation/Temozolomide-Treated Glioblastoma Patients

    Directory of Open Access Journals (Sweden)

    Cameron J. Koch

    2014-12-01

    Full Text Available The standard of care for glioblastoma (GB is surgery followed by concurrent radiation therapy (RT and temozolomide (TMZ and then adjuvant TMZ. This regime is associated with increased survival but also increased occurrence of equivocal imaging findings, e.g., tumor progression (TP versus treatment effect (TE, which is also referred to as pseudoprogression (PsP. Equivocal findings make decisions regarding further treatment difficult and often delayed. Because none of the current imaging assays have proven sensitive and specific for differentiation of TP versus TE/PsP, we investigated whether blood-derived microvesicles (MVs would be a relevant assay. METHODS: 2.8 ml of citrated blood was collected from patients with GB at the time of their RT simulation, at the end of chemoradiation therapy (CRT, and multiple times following treatment. MVs were collected following multiple centrifugations (300g, 2500g, and 15,000g. The pellet from the final spin was analyzed using flow cytometry. A diameter of approximately 300 nm or greater and Pacific Blue–labeled Annexin V positivity were used to identify the MVs reported herein. RESULTS: We analyzed 19 blood samples from 11 patients with GB. MV counts in the patients with stable disease or TE/PsP were significantly lower than patients who developed TP (P = .014. CONCLUSION: These preliminary data suggest that blood analysis for MVs from GB patients receiving CRT may be useful to distinguish TE/PsP from TP. MVs may add clarity to standard imaging for decision making in patients with equivocal imaging findings.

  18. Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freedland, Stephen J., E-mail: steve.freedland@duke.edu [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Gerber, Leah [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S. [Myriad Genetics, Inc, Salt Lake City, Utah (United States); Salama, Joseph K. [Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Stone, Steven [Myriad Genetics, Inc, Salt Lake City, Utah (United States)

    2013-08-01

    Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

  19. Progressive increase in cavitation with the evolution of fungus ball: A clue to the diagnosis of chronic necrotizing pulmonary aspergillosis

    OpenAIRE

    Prasad R.; Garg Sanjay

    2009-01-01

    Chronic necrotizing pulmonary aspergillosis (CNPA) is an uncommon pulmonary infection seen in the patients with chronic obstructive pulmonary disease, bronchiectasis, pneumoconiosis, diabetes mellitus, alcoholism, poor nutrition or low dose corticosteroid therapy. Here, we are presenting a case of CNPA with diabetes mellitus that was misdiagnosed as pulmonary tuberculosis.

  20. Progressive increase in cavitation with the evolution of fungus ball: A clue to the diagnosis of chronic necrotizing pulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    Prasad R

    2009-01-01

    Full Text Available Chronic necrotizing pulmonary aspergillosis (CNPA is an uncommon pulmonary infection seen in the patients with chronic obstructive pulmonary disease, bronchiectasis, pneumoconiosis, diabetes mellitus, alcoholism, poor nutrition or low dose corticosteroid therapy. Here, we are presenting a case of CNPA with diabetes mellitus that was misdiagnosed as pulmonary tuberculosis.

  1. Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score.

    Science.gov (United States)

    Christopoulos, Georgios; Kandzari, David E; Yeh, Robert W; Jaffer, Farouc A; Karmpaliotis, Dimitri; Wyman, Michael R; Alaswad, Khaldoon; Lombardi, William; Grantham, J Aaron; Moses, Jeffrey; Christakopoulos, Georgios; Tarar, Muhammad Nauman J; Rangan, Bavana V; Lembo, Nicholas; Garcia, Santiago; Cipher, Daisha; Thompson, Craig A; Banerjee, Subhash; Brilakis, Emmanouil S

    2016-01-11

    This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach. Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning. We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2:1 sampling ratio). Variables with strong association with technical success in multivariable analysis were assigned 1 point, and a 4-point score was developed from summing all points. The PROGRESS CTO score was subsequently compared with the J-CTO (Multicenter Chronic Total Occlusion Registry in Japan) score in the validation cohort. Technical success was 92.9%. On multivariable analysis, factors associated with technical success included proximal cap ambiguity (beta coefficient [b] = 0.88), moderate/severe tortuosity (b = 1.18), circumflex artery CTO (b = 0.99), and absence of "interventional" collaterals (b = 0.88). The resulting score demonstrated good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow chi-square = 2.633; p = 0.268, and receiver-operator characteristic [ROC] area = 0.778) and validation (Hosmer-Lemeshow chi-square = 5.333; p = 0.070, and ROC area = 0.720) subset. In the validation cohort, the PROGRESS CTO and J-CTO scores performed similarly in predicting technical success (ROC area 0.720 vs. 0.746, area under the curve difference = 0.026, 95% confidence interval = -0.093 to 0.144). The PROGRESS CTO score is a novel useful tool for estimating technical success in CTO PCI performed using the hybrid approach. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US

    Science.gov (United States)

    Adams, Edgar H; McElroy, Heather J; Udall, Margarita; Masters, Elizabeth T; Mann, Rachael M; Schaefer, Caroline P; Cappelleri, Joseph C; Clair, Andrew G; Hopps, Markay; Daniel, Shoshana R; Mease, Philip; Silverman, Stuart L; Staud, Roland

    2016-01-01

    Background A previous fibromyalgia (FM) research reports that 20%–47% of diagnosed patients may not meet the study definition of FM 1–2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. Methods This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP) diagnosis stability over time. At enrollment (baseline), subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months), visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM), FM−CWP+ (screened positive for CWP but did not receive physician diagnosis of FM), and FM−CWP− (screened negative for CWP). Approximately 2 years later (follow-up), subjects were reassessed at the same study site and completed a questionnaire with the same patient-reported outcomes. Results Seventy-six FM+CWP+ subjects completed assessments at both time points; 56 (73.7%) met the FM study definition at follow-up. Twenty subjects no longer met the FM study definition (eleven became FM−CWP− and nine became FM−CWP+). Ten subjects (two from FM−CWP− and eight from FM−CWP+) transitioned into the FM+CWP+ group at follow-up; they reported more tender points and pain interference with sleep and worse physical function at baseline compared with subjects who did not transition to FM+CWP+. Most (76.7%) of the subjects who transitioned into/out of FM+CWP+ experienced changes in CWP, number of positive tender points, or both. Conclusion The results suggest that some FM+CWP+ patients experience

  3. No adaptive response is induced by chronic low-dose radiation from Ra-226 in the CHSE/F fish embryonic cell line and the HaCaT human epithelial cell line.

    Science.gov (United States)

    Shi, Xiaopei; Mothersill, Carmel; Seymour, Colin

    2016-11-01

    To determine whether chronic low-dose α-particle radiation from Ra-226 over multiple cell generations can lead to an adaptive response in CHSE/F fish embryonic cells or HaCaT human epithelial cells receiving subsequent acute high-dose γ-ray radiation. CHSE/F and HaCaT cells were exposed to very low doses of Ra-226 in medium for multiple generations prior to being challenged by a higher dose γ-ray radiation. The clonogenic assay was used to test the clonogenic survival of cells with or without being pretreated by radiation from Ra-226. In general, pretreatment with chronic radiation has no significant influence on the reaction of cells to the subsequent challenge radiation. Compared to unprimed cells, the change in clonogenic survival of primed cells after receiving challenge radiation is mainly due to the influence of the chronic exposure, and there's little adaptive response induced. However at several dose points, pretreatment of CHSE/F fish cells with chronic radiation resulted in a radiosensitive response to a challenge dose of γ-ray radiation, and pretreatment of HaCaT cells resulted in no effect except for a slightly radioresistant response to the challenge radiation which was not significant. The results suggest that chronic low-dose radiation is not effective enough to induce adaptive response. There was a difference between human and fish cells and it may be important to consider results from multiple species before making conclusions about effects of chronic or low doses of radiation in the environment. The term "radiosensitive" or "adaptive" make no judgment about whether such responses are ultimately beneficial or harmful. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effectiveness of home-based cupping massage compared to progressive muscle relaxation in patients with chronic neck pain--a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Romy Lauche

    Full Text Available UNLABELLED: Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity (0-100 mm visual analog scale; VAS after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female were randomized to cupping massage (n = 30 or progressive muscle relaxation (n = 31. After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results. TRIAL REGISTRATION: ClinicalTrials.gov NCT01500330.

  5. Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Tseng CW

    2016-03-01

    Full Text Available Chih-Wei Tseng,1,2 Ting-Tsung Chang,3,4 Shinn-Jia Tzeng,5 Yu-Hsi Hsieh,1,2 Tsung-Hsing Hung,1,2 Hsiang-Ting Huang,6 Shu-Fen Wu,7 Kuo-Chih Tseng1,2 1Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, 2School of Medicine, Tzuchi University, Hualien, 3Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, 4Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, 5Department of Agronomy, National Chiayi University, 6Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 7Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan Objective: We studied the effect of sustained virologic response (SVR after treatment with pegylated-interferon (PEG-IFN plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC. Patients and methods: This retrospective study enrolled 145 elderly CHC patients (aged ≥65 years who were treatment-naïve and were treated with PEG-IFN plus ribavirin for 6 months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3–6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. Results: The mean patient age was 69.1±3.3 years, and the average follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1–12.3 years. Ninety-five patients (65.5% achieved SVR, and 26 (17.9% discontinued treatment. Twenty-seven patients (18.6% developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312–8.761, P=0.012. The

  6. Progress report: nuclear safety and radiation protection in France in 2005; Rapport annuel: la surete nucleaire et la radioprotection en France en 2005

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    The Asn (Nuclear safety authority) considers that 2005 was a satisfactory year in terms of nuclear safety and radiation protection. However, further progress can and must be made. 2005 was a year of great progress for the Asn as it consolidated its organisation and working methods, in accordance with the 2005-2007 strategic plan it set for itself. The Asn continued progress in the field of radiation protection has given rise to various new regulations to improve the legislative and regulatory framework in this area. 2005 was marked by significant progress in the process of harmonizing national nuclear safety policies Against a backdrop of the preparation of a bill on management of radioactive materials and waste, to be presented to Parliament in March 2006, 2005 was a year of important milestones. The Asn control activities encompass the following seven areas: development of general regulations for nuclear safety and radiation protection; management of individual authorization requests and receipt of declarations; inspection of nuclear activities; organisation of radiological surveillance of individuals and of the environment; preparation for management of emergency situations and implementation if necessary; contribution to public information on nuclear safety and radiation protection; determination of the French position within international community. Main topics in 2005: government bill on transparency and security in the nuclear field; the challenges and ambitions of the Asn; controlling exposure to radon; EPR Reactor Project Safety; working towards a law on radioactive waste in 2006; I.R.R.T.: an international audit of Asn in 2006; harmonization of nuclear safety in Europe; Chernobyl: what has been achieved over the past 20 years; informing the Public; internal authorizations. (N.C.)

  7. Does MW Radiation Affect Gene Expression, Apoptotic Level, and Cell Cycle Progression of Human SH-SY5Y Neuroblastoma Cells?

    Science.gov (United States)

    Kayhan, Handan; Esmekaya, Meric Arda; Saglam, Atiye Seda Yar; Tuysuz, Mehmed Zahid; Canseven, Ayşe Gulnihal; Yagci, Abdullah Munci; Seyhan, Nesrin

    2016-06-01

    Neuroblastoma (NB) is a cancer that occurs in sympathetic nervous system arising from neuroblasts and nerve tissue of the adrenal gland, neck, chest, or spinal cord. It is an embryonal malignancy and affects infants and children. In this study, we investigated the effects of microwave (MW) radiation on apoptotic activity, cell viability, and cell cycle progression in human SH-SY5Y NB cells which can give information about MW radiation effects on neural cells covering the period from the embryonic stages to infants. SH-SY5Y NB cells were exposed to 2.1 GHz W-CDMA modulated MW radiation for 24 h at a specific absorption rate of 0.491 W/kg. Control samples were in the same conditions with MW-exposed samples but they were not exposed to MW radiation. The apoptotic activity of cells was measured by Annexin-V-FITC and propidium iodide staining. Moreover, mRNA levels of proliferative and cell cycle proteins were determined by real-time RT-PCR. The change in cell cycle progression was observed by using CycleTest-Plus DNA reagent. No significant change was observed in apoptotic activity of MW-exposed cells compared to control cells. The mRNA levels of c-myc and cyclin D1 were significantly reduced in MW group (p CDMA modulated MW radiation did not cause apoptotic cell death but changed cell cycle progression.

  8. Radiation forces and torque on a rigid elliptical cylinder in acoustical plane progressive and (quasi)standing waves with arbitrary incidence

    CERN Document Server

    Mitri, F G

    2016-01-01

    Analytical expressions for the axial and transverse acoustic radiation forces as well as the radiation torque per length are derived for a rigid elliptical cylinder placed arbitrarily in the field of in plane progressive, quasi-standing or standing waves. The rigid elliptical cylinder case is important to be considered as a first-order approximation of the behavior of a fluid particle suspended in air, because of the significant acoustic impedance mismatch at the particle's boundary. Based on the partial-wave series expansion method in cylindrical coordinates, non-dimensional acoustic radiation force and torque functions are derived and defined in terms of the scattering coefficients of the elliptic cylinder. A coupled system of linear equations is obtained after applying the Neumann boundary condition for an immovable surface in a non-viscous fluid, and solved numerically by matrix inversion after performing a single numerical integration procedure. Computational results for the non-dimensional force compone...

  9. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis: A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

    Directory of Open Access Journals (Sweden)

    Wang Qi

    2012-08-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. Results Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228 weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. Conclusions Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.

  10. Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation.

    Science.gov (United States)

    Souza, Ana Carolina P; Bocharov, Alexander V; Baranova, Irina N; Vishnyakova, Tatyana G; Huang, Yuning G; Wilkins, Kenneth J; Hu, Xuzhen; Street, Jonathan M; Alvarez-Prats, Alejandro; Mullick, Adam E; Patterson, Amy P; Remaley, Alan T; Eggerman, Thomas L; Yuen, Peter S T; Star, Robert A

    2016-04-01

    Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein A-I-mimetic peptide 5A antagonizes CD36 in vitro. To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild-type to CD36 knockout mice and wild-type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild-type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild-type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreased renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression.

  11. Case of radiation myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Noriyoshi; Iwamoto, Toshihiko; Hagiwara, Akiyoshi; Sato, Yoshihito; Shimizu, Nobuya; Takagi, Yasushi

    1988-03-01

    A 72-year-old woman presented with right hemiparesthesia and left hemiparalysis. At the age of 63, the patient was treated with pre- and post-operative radiation with a total dose of 100 Gy for maxillary squamous cell carcinoma. Five years later, a dose of 50 Gy was delivered again to the head and neck because of the suspicion of recurrence. Magnetic resonance imaging showed flat and thinned cervical spine on the transverse section and markedly atrophied cervical spine at the C1 to C3 levels on the sagittal section. She was diangosed as having chronic progressive radiation myelopathy in view of a history of large doses of radiation to the head and neck. (Namekawa, K.).

  12. Impairment-Based 3-D Robotic Intervention Improves Upper Extremity Work Area in Chronic Stroke: Targeting Abnormal Joint Torque Coupling With Progressive Shoulder Abduction Loading

    Science.gov (United States)

    Ellis, Michael D.; Sukal-Moulton, Theresa M.; Dewald, Julius P. A.

    2010-01-01

    The implementation of a robotic system (ACT3D) that allowed for a quantitative measurement of abnormal joint torque coupling in chronic stroke survivors and, most importantly, a quantitative means of initiating and progressing an impairment-based intervention, is described. Individuals with chronic moderate to severe stroke (n = 8) participated in this single-group pretest-posttest design study. Subjects were trained over eight weeks by progressively increasing the level of shoulder abduction loading experienced by the participant during reaching repetitions as performance improved. Reaching work area was evaluated pre- and postintervention for ten different shoulder abduction loading levels along with isometric single-joint strength and a qualitative clinical assessment of impairment. There was a significant effect of session (pre versus post) with an increase in reaching work area, despite no change in single-joint strength. This data suggests that specifically targeting the abnormal joint torque coupling impairment through progressive shoulder abduction loading is an effective strategy for improving reaching work area following hemiparetic stroke. Application of robotics, namely, the ACT3D, allowed for quantitative control of the exercise parameters needed to directly target the synergistic coupling impairment. The targeted reduction of abnormal joint torque coupling is likely the key factor explaining the improvements in reaching range of motion achieved with this intervention. PMID:20657711

  13. Axl tyrosine kinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia.

    Directory of Open Access Journals (Sweden)

    Gareth D Hyde

    Full Text Available Chronic kidney disease (CKD is defined as the progressive loss of renal function often involving glomerular, tubulo-interstitial and vascular pathology. CKD is associated with vascular calcification; the extent of which predicts morbidity and mortality. However, the molecular regulation of these events and the progression of chronic kidney disease are not fully elucidated. To investigate the function of Axl receptor tyrosine kinase in CKD we performed a sub-total nephrectomy and fed high phosphate (1% diet to Axl+/+ and Axl-/- mice. Plasma Gas6 (Axl' ligand, renal Axl expression and downstream Akt signalling were all significantly up-regulated in Axl+/+ mice following renal mass reduction and high phosphate diet, compared to age-matched controls. Axl-/- mice had significantly enhanced uraemia, reduced bodyweight and significantly reduced survival following sub-total nephrectomy and high phosphate diet compared to Axl+/+ mice; only 45% of Axl-/- mice survived to 14 weeks post-surgery compared to 87% of Axl+/+ mice. Histological analysis of kidney remnants revealed no effect of loss of Axl on glomerular hypertrophy, calcification or renal sclerosis but identified significantly increased tubulo-interstitial apoptosis in Axl-/- mice. Vascular calcification was not induced in Axl+/+ or Axl-/- mice in the time frame we were able to examine. In conclusion, we identify the up-regulation of Gas6/Axl signalling as a protective mechanism which reduces tubulo-interstitial apoptosis and slows progression to end-stage renal failure in the murine nephrectomy and high phosphate diet model of CKD.

  14. Axl tyrosine kinase protects against tubulo-interstitial apoptosis and progression of renal failure in a murine model of chronic kidney disease and hyperphosphataemia.

    Science.gov (United States)

    Hyde, Gareth D; Taylor, Rebecca F; Ashton, Nick; Borland, Samantha J; Wu, Hon Sing Geoffrey; Gilmore, Andrew P; Canfield, Ann E

    2014-01-01

    Chronic kidney disease (CKD) is defined as the progressive loss of renal function often involving glomerular, tubulo-interstitial and vascular pathology. CKD is associated with vascular calcification; the extent of which predicts morbidity and mortality. However, the molecular regulation of these events and the progression of chronic kidney disease are not fully elucidated. To investigate the function of Axl receptor tyrosine kinase in CKD we performed a sub-total nephrectomy and fed high phosphate (1%) diet to Axl+/+ and Axl-/- mice. Plasma Gas6 (Axl' ligand), renal Axl expression and downstream Akt signalling were all significantly up-regulated in Axl+/+ mice following renal mass reduction and high phosphate diet, compared to age-matched controls. Axl-/- mice had significantly enhanced uraemia, reduced bodyweight and significantly reduced survival following sub-total nephrectomy and high phosphate diet compared to Axl+/+ mice; only 45% of Axl-/- mice survived to 14 weeks post-surgery compared to 87% of Axl+/+ mice. Histological analysis of kidney remnants revealed no effect of loss of Axl on glomerular hypertrophy, calcification or renal sclerosis but identified significantly increased tubulo-interstitial apoptosis in Axl-/- mice. Vascular calcification was not induced in Axl+/+ or Axl-/- mice in the time frame we were able to examine. In conclusion, we identify the up-regulation of Gas6/Axl signalling as a protective mechanism which reduces tubulo-interstitial apoptosis and slows progression to end-stage renal failure in the murine nephrectomy and high phosphate diet model of CKD.

  15. The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

    OpenAIRE

    Blumenfeld, P; Pfeffer, R M; Symon, Z; Den, R B; Dicker, A.P.; Raben, D.; Lawrence, Y R

    2014-01-01

    Background: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT–drug development programmes before patent expiration. Methods: We identified novel drug–radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: da...

  16. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay.

    Science.gov (United States)

    Kumar, P R Vivek; Seshadri, M; Jaikrishan, G; Das, Birajalaxmi

    2015-05-01

    This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year(-1)), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N=43, range 1.07 mSv year(-1) to 5.55 mSv year(-1)) and 9.62 mSv (N = 34, range 6.07 mSv year(-1) to 17.41 mSv year(-1)), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P=0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from our study suggest in vivo chronic low-level natural radiation provides an initial exposure that allows an adaptation to a subsequent higher radiation exposure, perhaps through improving DNA repair via an unknown mechanism. Therefore, further investigations would be necessary in this population to understand the biological and health effects of chronic low-level natural radiation exposures. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Progress Report for "Developing a Proactive Framework for Adaptive Management of Chronic Wasting Disease on the National Elk Refuge"

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Hobbs, Monello, and Kauffman have been granted funds to develop a Bayesian state space model to support adaptive management of Chronic Wasting Disease (CWD) in the...

  18. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study.

    Science.gov (United States)

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-04-01

    The kidney is one of the organs most prominently affected by aging. This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons resulting in hyperfiltration, hypertrophy and elevations in glomerular pressure. The factors influencing aging of the kidney are not fully elucidated. Epidemiological, experimental and interventional studies resulted in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease (CKD). Therefore, we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18-65 years with primary non-diabetic CKD of various degrees of renal impairment. Of them, 177 completed a prospective follow-up of 7 years. Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and/or terminal renal failure. Patients who reached a progression endpoint (n =6 5) were significantly older, had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate (GFR). Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis. Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters. As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished. In summary, our prospective 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression.

  19. 慢性乙型肝炎与糖尿病的研究进展%Research Progress of Chronic Hepatitis B and Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    孙芳芳

    2012-01-01

    Recent studies have shown that chronic hepatitis B and diabetes are closely related, chronic hepatitis B could cause pathoglycemia,and even induce diabetes, mechanisms of which are associated with insulin resistance, impaired liver function, hepatic steatosis, hepatitis B virus replication in pancreas, pancreatic injury and autoimmune reactions,clinical use of interferon. Vice versa, insulin resistance and diabetes can accelerate the progression to liver fibrosis and liver cancer of chronic hepatitis B. Here is to make a review on the current opinions of the relationship between chronic hepatitis B and diabetes.%已有研究表明慢性乙型肝炎与糖尿病密切相关,可引起血糖异常,甚至诱发糖尿病,其发生机制与胰岛素抵抗、肝功能受损、肝脂肪变、乙型肝炎病毒在胰腺复制、胰腺损伤及自身免疫反应、干扰素的应用等相关.反之,胰岛素抵抗及糖尿病亦可加速慢性乙型肝炎进展为肝纤维化及肝癌.现就慢性乙型肝炎与糖尿病关系的研究进展予以综述.

  20. Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered expression is not sufficient for progression from chronic pancreatitis to pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Yu; Eishi Nagai; Masao Tanaka; Kenoki Ohuchida; Kazuhiro Mizumoto; Nami Ishikawa; Yasuhiro Ogura; Daisuke Yamada; Takuya Egami; Hayato Fujita; Seiji Ohashi

    2006-01-01

    AIM: To investigate c-met expression during early pancreatic carcinogenesis.METHODS: We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative real time reverse transcription-polymerase chain reaction.RESULTS: In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues.c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microdissected pancreatic cancer cells and pancreatitisaffected epithelial cells than in normal ductal epithelial cells (both, P < 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells.CONCLUSION: Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.

  1. Acoustic radiation force impulse imaging for non-invasive assessment of renal histopathology in chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Qiao Hu

    Full Text Available OBJECTIVE: To investigate the stiffness values obtained by acoustic radiation force impulse (ARFI quantification in assessing renal histological fibrosis of chronic kidney disease (CKD. METHODS: 163 patients with CKD and 32 healthy volunteers were enrolled between June 2013 and April 2014. ARFI quantification, given as shear wave velocity (SWV, was performed to measure renal parenchyma stiffness. Diagnostic performance of ARFI imaging and conventional ultrasound (US were compared with histologic scores at renal biopsy. Intra- and inter-observer reliability of SWV measurement was analyzed. RESULTS: In CKD patients, SWV measurements correlated significantly with pathological parameters (r = -0.422--0.511, P<0.001, serum creatinine (r = -0.503, P<0.001, and glomerular filtration rate (r = 0.587, P<0.001. The mean SWV in kidneys with severely impaired (histologic score: ≥19 points was significant lower than that mildly impaired (histologic score: ≤9 points, moderately impaired (histologic score: 10-18 points, and control groups (all P<0.001. Receiver operating characteristic (ROC curves analyses indicated that the area under the ROC curve for the diagnosis of renal histological fibrosis using ARFI imaging was superior to these conventional US parameters. Using the optimal cut-off value of 2.65 m/s for the diagnosis of mildly impaired kidneys, 2.50 m/s for moderately impaired kidneys, and 2.33 m/s for severely impaired kidneys, the corresponding area under the ROC curves were 0.735, 0.744, and 0.895, respectively. Intra- and intre-observer agreement of SWV measurements were 0.709 (95% CI: 0.390-0.859, P<0.001 and 0.627 (95% CI: 0.233-0.818, P = 0.004, respectively. CONCLUSIONS: ARFI may be an effective tool for evaluating renal histological fibrosis in CKD patients.

  2. Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

    Directory of Open Access Journals (Sweden)

    Vanessa Fiorini Furtado

    2015-10-01

    Full Text Available BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin 12 months (p-value = 0.030.CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

  3. 中医药治疗慢性泄泻的研究进展*%Study Progress of Traditional Chinese Medicine Treating Chronic Diarrhea

    Institute of Scientific and Technical Information of China (English)

    吴文康; 何婷; 钟育敏; 黄应培

    2013-01-01

      通过对近年来中医药治疗慢性泄泻的文献进行整理、归纳、分析,综合了中医对本病治疗方面的进展,认为中医药治疗本病方法多样、疗效肯定、副作用少,具有明显优势。%According to collating, concluding and analyzing the literature referring to traditional Chinese medicine treating chronic diarrhea in recent years, this paper summarizes the progress of traditional Chinese medicine treating chronic diarrhea, the methods of which is various, with efficacy definite and less side effects, which is of obvious advantages.

  4. Study of the radiation effects on nucleic acids and related compounds. Annual progress report, August 15, 1974--August 14, 1975. [X radiation, hamster cells, Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.Y.

    1975-01-01

    Interest is being centered on the chemical and physical nature of radiation-induced lesions to nucleic acids and their components. These investigations have revealed the enormous complexity of chemical events in these systems and the possible degradation of nucleic acids by strand breakage. Therefore, work in the ionizing radiation of DNA and its components has proceeded along a dual course. For chemical studies, our prime concern is the stepwise isolation and identification of the radiation products of derivatives of pyrimidines and the study of the actual mechanisms of their formation. For biological studies, H. influenzae cells, the Chinese hamster V79B-1 cell line, and the Dunn osteosarcoma lung colony system were used. During the last year, the method of synthesis of 5-hydroperoxymethyluracil (T/sub ..cap alpha../OOH) was greatly improved. Large-scale preparation of 5-hydroxy-6-hydroperoxy-5,6-dihydrothymine (T/sup 6/OOH) were carried out in order to study the action of T/sup 6/OOH on neighboring bases, glycosidic bond-breakage, cell mutagenesis, chromosomal aberrations, and possible synergistic effects on x radiation. These results allow one to relate radiobiological effects with radiation chemical changes in DNA.

  5. NRC TLD Direct Radiation Monitoring Network. Volume 15, No. 4: Quarterly progress report, October--December 1995

    Energy Technology Data Exchange (ETDEWEB)

    Struckmeyer, R.

    1996-03-01

    This report presents the results of the NRC Direct Radiation Monitoring Network for the fourth quarter of 1995. It provides the ambient radiation levels measured in the vicinity of 75 sites throughout the United States. In addition, it describes the equipment used, monitoring station selection criteria, characterization of the dosimeter response, calibration procedures, statistical methods, intercomparison, and quality assurance program.

  6. Progress Toward Electrostatic Radiation Shielding of Interplanetary Spacecraft: Strategies, Concepts and Technical Challenges of Human Exploration Beyond Low Earth Orbit

    Science.gov (United States)

    Metzger, Philip T.; Lane, John E.; Youngquist, Robert C.

    2004-01-01

    The radiation problem is a serious obstacle to solar system exploration. Electrostatic shielding was previously dismissed as unworkable. This was based on the false assumption that radial symmetry is needed to provide isotropic protection. KSC recently demonstrated the feasibility of asymmetric, multipole electrostatic shielding. Combined with passive shielding it might solve the radiation problem

  7. PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

    Science.gov (United States)

    Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

    At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m(2)/year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m(2)/year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m(2)/year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  8. No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease.

    Science.gov (United States)

    Mehrotra, Rajnish; Peralta, Carmen A; Chen, Shu-Cheng; Li, Suying; Sachs, Michael; Shah, Anuja; Norris, Keith; Saab, Georges; Whaley-Connell, Adam; Kestenbaum, Bryan; McCullough, Peter A

    2013-11-01

    Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16-10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.

  9. Selective depletion of a minor subpopulation of B-chronic lymphocytic leukemia cells is followed by a delayed but progressive loss of bulk tumor cells and disease regression

    Directory of Open Access Journals (Sweden)

    Goodell Margaret A

    2009-11-01

    Full Text Available Abstract Cancer precursor/progenitor cells may initiate and sustain the growth of tumors, but evidence for their existence in human disease is indirect, relying on their in vitro properties and animal models. More directly, specific elimination of these rare cells from cancer patients should produce a delayed but progressive disappearance of differentiated malignant progeny. Here, we describe selective eradication of a putative precursor population in a patient with B-cell chronic lymphocytic leukemia, followed 6 months later by a progressive loss of mature tumor cells without further treatment. This outcome supports the presence of a rare population of precursor/progenitor cells in human malignancies, and suggests benefit from their removal.

  10. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  11. Axial acoustic radiation force on rigid oblate and prolate spheroids in Bessel vortex beams of progressive, standing and quasi-standing waves

    CERN Document Server

    Mitri, F G

    2016-01-01

    The analysis using the partial-wave series expansion (PWSE) method in spherical coordinates is extended to evaluate the acoustic radiation force experienced by rigid oblate and prolate spheroids centered on the axis of wave propagation of high-order Bessel vortex beams composed of progressive, standing and quasi-standing waves, respectively. A coupled system of linear equations is derived after applying the Neumann boundary condition for an immovable surface in a non-viscous fluid, and solved numerically by matrix inversion after performing a single numerical integration procedure. The system of linear equations depends on the partial-wave index n and the order of the Bessel vortex beam m using truncated but converging PWSEs in the least-squares sense. Numerical results for the radiation force function, which is the radiation force per unit energy density and unit cross-sectional surface, are computed with particular emphasis on the amplitude ratio describing the transition from the progressive to the pure st...

  12. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1997-01-01

    The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurements of downstream renal artery resistance. PI and RI have been found to correlate with renal vascular resistance, filtration fraction and effective renal plasma flow in chronic renal failure. The aim...... of the present study was to evaluate the potential relationship between these indices and the rate of decline in renal function, as reflected by changes in different parameters of renal function in patients with chronic renal failure....

  13. [Development and recommendations in the area of ionizing and nonionizing radiations]. Progress report, 1 September 1991--30 April 1992

    Energy Technology Data Exchange (ETDEWEB)

    1992-09-01

    This report briefly describes seven publications produced in 1991--1992 under the auspices of the National Council on Radiation Protection and Measurements. In addition current status of additional publications in preparation are outlined.

  14. Nanodosimetry and nanodosimetric-based models of radiation action for radon alpha particles. Progress report, July 1990--June 1992

    Energy Technology Data Exchange (ETDEWEB)

    Zaider, M.

    1992-12-31

    We report on a theory for describing the biological effects of ionizing radiation in particular radon {alpha} particles. Behind this approach is the recognition that biological effects such as chromosome aberrations, cellular transformation, cellular inactivation, etc, are the result of a hierarchic sequence of radiation effects. We indicate how to treat each of the individual processes in this sequence, and also how to relate one effect to the hierarchically superior one.

  15. Combined effect of the environmental factors as ionizing radiation and a chronic iodine deficiency on the thyroid gland and the immune condition

    Energy Technology Data Exchange (ETDEWEB)

    Danyarova, L. [Department of Endocrynology, Research Institute of Cardiology and Internal Medicine, Almaty (Kazakhstan)

    2012-07-01

    The Semipalatinsk Test Site was the primary testing venue for the Soviet Union's nuclear weapons. It is located on the steppe in northeast Kazakhstan. The tragic situation of the Semipalatinsk region is an acute and chronic radiation, repeated in big and small doses and a total absence of territorial decontamination, created unique conditions for study of the long term influence of the radiation doses on the health of the population. The Semipalatinsk region of the Republic of Kazakhstan belongs also to an area of moderate and pronounced iodine deficiency. The purpose of the research is to study the prevalence of a thyroid gland pathology and the condition of a cytokine immune link that is likely to be influenced by a combine effect of ionizing radiation and a chronic iodine deficiency. 1100 people passed through the investigation and it appears that 56, 75% of them had a thyroid pathology. Thyroid gland functional condition analysis (TSH, FT3, FT4 a-TG, a-TPO) has shown the prevalence of a subclinical hypothyroidism (33%). 28, 8% resulted in the presence of antibodies to thyroglobulin and the thyroid peroxides, whereas in the areas located further to the nuclear range, the percentage was only 13, 0%

  16. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1997-01-01

    The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurements of downstream renal artery resistance. PI and RI have been found to correlate with renal vascular resistance, filtration fraction and effective renal plasma flow in chronic renal failure. The aim...

  17. Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy.

    Science.gov (United States)

    Kelly, Katherine J; Zhang, Jizhong; Han, Ling; Wang, Mingsheng; Zhang, Shaobo; Dominguez, Jesus H

    2013-12-15

    Diabetic nephropathy, the most common cause of progressive chronic renal failure and end-stage renal disease, has now reached global proportions. The only means to rescue diabetic patients on dialysis is renal transplantation, a very effective therapy but severely limited by the availability of donor kidneys. Hence, we tested the role of intravenous renal cell transplantation (IRCT) on obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS male tubular cells was given intravenously at 15 and 20 wk of age. Rats were euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong and long-lasting beneficial effects on renal function and structure, including tubules and glomeruli. However, donor cells were found engrafted only in renal tubules 14 wk after the second infusion. The results indicate that IRCT with serum amyloid A-positive cells is effective in preventing the progression of chronic kidney disease in rats with diabetic and ischemic nephropathy.

  18. Identifying patients with advanced chronic conditions for a progressive palliative care approach: a cross-sectional study of prognostic indicators related to end-of-life trajectories

    Science.gov (United States)

    Amblàs-Novellas, J; Murray, S A; Espaulella, J; Martinez-Muñoz, M; Blay, C; Gómez-Batiste, X

    2016-01-01

    Objectives 2 innovative concepts have lately been developed to radically improve the care of patients with advanced chronic conditions (PACC): early identification of palliative care (PC) needs and the 3 end-of-life trajectories in chronic illnesses (acute, intermittent and gradual dwindling). It is not clear (1) what indicators work best for this early identification and (2) if specific clinical indicators exist for each of these trajectories. The objectives of this study are to explore these 2 issues. Setting 3 primary care services, an acute care hospital, an intermediate care centre and 4 nursing homes in a mixed urban–rural district in Barcelona, Spain. Participants 782 patients (61.5% women) with a positive NECPAL CCOMS-ICO test, indicating they might benefit from a PC approach. Outcome measures The characteristics and distribution of the indicators of the NECPAL CCOMS-ICO tool are analysed with respect to the 3 trajectories and have been arranged by domain (functional, nutritional and cognitive status, emotional problems, geriatric syndromes, social vulnerability and others) and according to their static (severity) and dynamic (progression) properties. Results The common indicators associated with early end-of-life identification are functional (44.3%) and nutritional (30.7%) progression, emotional distress (21.9%) and geriatric syndromes (15.7% delirium, 11.2% falls). The rest of the indicators showed differences in the associations per illness trajectories (ppalliative approach. PMID:27645556

  19. Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV Egyptian Patients.

    Science.gov (United States)

    Bader El Din, Noha Gamal; Salum, Ghada M; Anany, Mohamed A; Ibrahim, Marwa Khalil; Dawood, Reham Mohamed; Zayed, Naglaa; El Abd, Yasmine S; El-Shenawy, Reem; El Awady, Mostafa K

    2015-08-01

    To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus resistance (MxA) gene promoter region in relation to the status of hepatitis C virus (HCV) progression and response to combined interferon (IFN) in chronic HCV Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV genotype 4-infected patients who underwent combined IFN therapy and 50 healthy individuals. All subjects were genotyped for -88 MxA polymorphism by the restriction fragment length polymorphism technique. There was an increasing trend of response to combined IFN treatment as 34.9% of GG, 64.3% of GT, and 66.7% of TT genotypes were sustained responders (P=0.05). The T allele was significantly affecting the response rate more than G allele (P=0.032). Moreover, the hepatic fibrosis score and hepatitis activity were higher in GG genotypes compared with the GT and TT genotypes. The multivariate analysis showed that the MxA GG genotype was an independent factor increasing the no response to IFN therapy (P=0.04, odds ratio [OR] 3.822, 95% confidence interval [CI] 1.056-11.092), also MxA G allele (P=0.0372, OR 2.905, 95% CI 1.066-7.919). MxA -88 polymorphism might be a potential biomarker to predict response to IFN and disease progression in chronic HCV-infected patients.

  20. Elucidation of changes in molecular signalling leading to increased cellular transformation in oncogenically progressed human bronchial epithelial cells exposed to radiations of increasing LET.

    Science.gov (United States)

    Ding, Liang-Hao; Park, Seongmi; Xie, Yang; Girard, Luc; Minna, John D; Story, Michael D

    2015-09-01

    The early transcriptional response and subsequent induction of anchorage-independent growth after exposure to particles of high Z and energy (HZE) as well as γ-rays were examined in human bronchial epithelial cells (HBEC3KT) immortalised without viral oncogenes and an isogenic variant cell line whose p53 expression was suppressed but that expressed an active mutant K-RAS(V12) (HBEC3KT-P53KRAS). Cell survival following irradiation showed that HBEC3KT-P53KRAS cells were more radioresistant than HBEC3KT cells irrespective of the radiation species. In addition, radiation enhanced the ability of the surviving HBEC3KT-P53RAS cells but not the surviving HBEC3KT cells to grow in anchorage-independent fashion (soft agar colony formation). HZE particle irradiation was far more efficient than γ-rays at rendering HBEC3KT-P53RAS cells permissive for soft agar growth. Gene expression profiles after radiation showed that the molecular response to radiation for HBEC3KT-P53RAS, similar to that for HBEC3KT cells, varies with radiation quality. Several pathways associated with anchorage independent growth, including the HIF-1α, mTOR, IGF-1, RhoA and ERK/MAPK pathways, were over-represented in the irradiated HBEC3KT-P53RAS cells compared to parental HBEC3KT cells. These results suggest that oncogenically progressed human lung epithelial cells are at greater risk for cellular transformation and carcinogenic risk after ionising radiation, but particularly so after HZE radiations. These results have implication for: (i) terrestrial radiation and suggests the possibility of enhanced carcinogenic risk from diagnostic CT screens used for early lung cancer detection; (ii) enhanced carcinogenic risk from heavy particles used in radiotherapy; and (iii) for space radiation, raising the possibility that astronauts harbouring epithelial regions of dysplasia or hyperplasia within the lung that contain oncogenic changes, may have a greater risk for lung cancers based upon their exposure to heavy

  1. Axial acoustic radiation force on rigid oblate and prolate spheroids in Bessel vortex beams of progressive, standing and quasi-standing waves.

    Science.gov (United States)

    Mitri, F G

    2017-02-01

    The analysis using the partial-wave series expansion (PWSE) method in spherical coordinates is extended to evaluate the acoustic radiation force experienced by rigid oblate and prolate spheroids centered on the axis of wave propagation of high-order Bessel vortex beams composed of progressive, standing and quasi-standing waves, respectively. A coupled system of linear equations is derived after applying the Neumann boundary condition for an immovable surface in a non-viscous fluid, and solved numerically by matrix inversion after performing a single numerical integration procedure. The system of linear equations depends on the partial-wave index n and the order of the Bessel vortex beam m using truncated but converging PWSEs in the least-squares sense. Numerical results for the radiation force function, which is the radiation force per unit energy density and unit cross-sectional surface, are computed with particular emphasis on the amplitude ratio describing the transition from the progressive to the pure standing waves cases, the aspect ratio (i.e., the ratio of the major axis over the minor axis of the spheroid), the half-cone angle and order of the Bessel vortex beam, as well as the dimensionless size parameter. A generalized expression for the radiation force function is derived for cases encompassing the progressive, standing and quasi-standing waves of Bessel vortex beams. This expression can be reduced to other types of beams/waves such as the zeroth-order Bessel non-vortex beam or the infinite plane wave case by appropriate selection of the beam parameters. The results for progressive waves reveal a tractor beam behavior, characterized by the emergence of an attractive pulling force acting in opposite direction of wave propagation. Moreover, the transition to the quasi-standing and pure standing wave cases shows the acoustical tweezers behavior in dual-beam Bessel vortex beams. Applications in acoustic levitation, particle manipulation and acousto

  2. 近年来辐射固化材料的研究进展%RESEARCH PROGRESS OF RADIATION CURING MATERIALS

    Institute of Scientific and Technical Information of China (English)

    杨永源

    2001-01-01

    综述了光化学、光自由基聚合、光引发剂UV固化、UV固化剂、电沉积光敏抗蚀剂和涂料、UV水基和粉末涂料及UV固化纳米复合材料的研究进展。%In this paper,research progress of radiation curing materials was reviewed.It included photochemistry,photo radical polymerization,photo initiator,UV curing agent,light sensitive resistant and photo sensitive coat in electrodeposition,UV curing aqueous or powdered coating and nanometer composite materials.

  3. Influence of Enalapril on the progression of chronic renal failure in diabetic nephropathy and nephropathies of and other aethiology: A two-year study

    Directory of Open Access Journals (Sweden)

    Trbojević Jasna

    2002-01-01

    Full Text Available Chronic renal failure (CRF is almost always associated with high arterial blood pressure. Adequate control of hypertension slows down the progression of the disease, Inhibitors of angiotenzin-converting enzyme (ACE inhibitors have proved to be very efficacious in decreasing high blood pressure. The aim of this study was to assess the influence of ACE inhibitor enalapril on the progression of CRF in patients with diabetic nephropathy and nephropathies of other origin. During 1998 and 1999 thirty patients (20 males and 10 females, aged 525+1.3 have been followed-up at the Department of Nephrology, Clinical Centre of Serbia. On regular monthly controls serum creatinine, urea, calcium and protein levels, creatinine clearance, and blood pressure, were measured. All patients were suggested a low protein diet. Progression of the disease was expressed by the slope of the regression line showing reciprocal serum creatinine values. Proteinaemia was significantly higher in diabetic patients after 12 months (p<0.35 but in the next 12 months the difference between groups disappeared. The same patients had significantly lower serum urea (p<0.05 after 24 months and creatinine values (p<0.05 dur ing the whole study. Other variables changed in the same manner and with similar progression in both groups. The direction of slope lines suggested recovery of kidney function in both examined groups. However, a smaller slope in patients with diabetic nephropathy together with other results showed that enalapril had better influence on slowing down the progression of CRF in this group of patients.

  4. RADIATION INDUCED PROGRESSIVE DECREASING IN THE EXPRESSION OF REVERSE TRANSCRIPTASE GENE OF hEST2 AND TELOMERASE ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objectives. In order to identify the relationship between telomerase and the biological effect of radiation injury,and investigate the role of human telomerase catalytic subunit gene (hEST2) reverse transcriptase(RT) segment in the expression of telomerase activity. Methods. Tumor HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60Co ray irradiation at RNA level and protein level. Quantitative PCR and Northern blotting were used to determine the expression of hEST2 RT segment that encodes seven motifs of the human telomeres, a PCR based telomeric repeat amplification protocol (TRAP)was used to assay telomerase activity after exposure to radiation. Results. Both of telomerase activity and the expression hEST2 RT segment were decreased with increasing dosage of radiation. In addition, testing the expression of motifs domain is similar to the measurement of telomerase activity. Conclusion. The detection of the hEST2 RT segment by Northern blotting and quantitative PCR are new methods for testing telomerase activity. Furthermore, radiation can cause a dose dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation.

  5. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  6. Radiation forces and torque on a rigid elliptical cylinder in acoustical plane progressive and (quasi)standing waves with arbitrary incidence

    Science.gov (United States)

    Mitri, F. G.

    2016-07-01

    This paper presents two key contributions; the first concerns the development of analytical expressions for the axial and transverse acoustic radiation forces exerted on a 2D rigid elliptical cylinder placed in the field of plane progressive, quasi-standing, or standing waves with arbitrary incidence. The second emphasis is on the acoustic radiation torque per length. The rigid elliptical cylinder case is important to be considered as a first-order approximation of the behavior of a cylindrical fluid column trapped in air because of the significant acoustic impedance mismatch at the particle boundary. Based on the rigorous partial-wave series expansion method in cylindrical coordinates, non-dimensional acoustic radiation force and torque functions are derived and defined in terms of the scattering coefficients of the elliptic cylinder. A coupled system of linear equations is obtained after applying the Neumann boundary condition for an immovable surface in a non-viscous fluid and solved numerically by matrix inversion after performing a single numerical integration procedure. Computational results for the non-dimensional force components and torque, showing the transition from the progressive to the (equi-amplitude) standing wave behavior, are performed with particular emphasis on the aspect ratio a/b, where a and b are the semi-axes of the ellipse, the dimensionless size parameter, as well as the angle of incidence ranging from end-on to broadside incidence. The results show that the elliptical geometry has a direct influence on the radiation force and torque, so that the standard theory for circular cylinders (at normal incidence) leads to significant miscalculations when the cylinder cross section becomes non-circular. Moreover, the elliptical cylinder experiences, in addition to the acoustic radiation force, a radiation torque that vanishes for the circular cylinder case. The application of the formalism presented here may be extended to other 2D surfaces of

  7. 慢性踝关节不稳的研究进展%Research Progress of Chronic Ankle Instability

    Institute of Scientific and Technical Information of China (English)

    刘欣; 黄真

    2015-01-01

    Ankle sprain is the most common injury of lower limbs. Without proper treatment,it is likely to develop chronic ankle instability. This paper summarized possible pathogenesis of chronic ankle instability, illustrated from the perspectives of proprioceptive disorder,dysfunction of neuromuscular and postural control and weakness of muscles around ankle joint,pointed out the rehabilitation programs which were often used,and provided suggestions for the clinical rehabilitation training of chronic ankle instability.%踝关节扭伤是下肢最常见的损伤,如未得到合理的处理很容易发展成为慢性踝关节不稳。本文归纳了慢性踝关节不稳可能的发病机制,从本体感觉障碍、神经肌肉控制不全、姿势控制功能不全及周围肌群肌力减退等方面进行了阐述,指出了目前常采用的康复训练方法及效果,为慢性踝关节不稳的临床康复训练提供建议。

  8. Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients

    NARCIS (Netherlands)

    M. Noordzij; E.M. Cranenburg; L.F. Engelsman; M.M. Hermans; E.W. Boeschoten; V.M. Brandenburg; W.J.W. Bos; J.P. Kooman; F.W. Dekker; M. Ketteler; L.J. Schurgers; R.T. Krediet; J.C. Korevaar

    2011-01-01

    Previous studies have shown that simple imaging methods may be useful for detection of vascular calcifications in dialysis patients. Based on annual, plain chest X-rays during follow-up on dialysis, we studied the associations of mineral metabolism with the presence and progression of aortic calcifi

  9. Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients.

    NARCIS (Netherlands)

    Noordzij, M.; Cranenburg, E.M.; Engelsman, L.F.; Hermans, M.M.; Boeschoten, E.W.; Brandenburg, V.M.; Bos, W.J.W.; Kooman, J.P.; Dekker, F.W.; Ketteler, M.; Schurgers, L.J.; Krediet, R.T.; Korevaar, J.C.

    2011-01-01

    Background. Previous studies have shown that simple imaging methods may be useful for detection of vascular calcifications in dialysis patients. Based on annual, plain chest X-rays during follow-up on dialysis, we studied the associations of mineral metabolism with the presence and progression of ao

  10. Diminished disease progression rate in a chronic kidney disease population following the replacement of dietary water source with quality drinking water: A pilot study.

    Science.gov (United States)

    Siriwardhana, Edirisinghe Arachchige Ranga Iroshanie Edirisinghe; Perera, Ponnamperuma Aratchige Jayasumana; Sivakanesan, Ramiah; Abeysekara, Tilak; Nugegoda, Danaseela Bandara; Weerakoon, Kosala; Siriwardhana, Dunusingha Asitha Surandika

    2017-03-29

    Environmental toxin/s is alleged to be the contributory factor for the chronic kidney disease of unknown etiology (CKDu) in Sri Lanka. The potential of drinking water as a medium for the nephrotoxic agents in the affected subjects has been comprehensively discoursed in the recent past. The present study was aimed to assess the effect of replacing the habitual drinking water on the kidney function of CKDu patients residing in the North Central Province of Sri Lanka: METHODS: An interventional study was carried out to assess the disease progression rate of a CKDu population whose habitual drinking water was replaced by bottled spring water certified by Sri Lanka Standard (SLS) for a period of 18 month along with a population of CKDu patients who continued with their usual drinking water. Kidney function of subjects in both groups were monitored in terms of blood pressure, serum creatinine, serum calcium, serum phosphorus, hemoglobin, estimated glomerular filtration rate and urinary protein at 6 months intervals during the intervention and follow up periods. Diminished disease progression rate was observed in CKDu patients in the intervention group when compared with the non- intervention group based on serum creatinine, Hb, estimated glomerular filtration rate and urinary protein levels. Extensive interventional studies are required to generalize effect of drinking water on CKDu population. The habitual drinking water is likely to be a contributory factor towards the progression of the disease. This article is protected by copyright. All rights reserved.

  11. Frequency and Absolute Number of FoxP3+ Regulatory T Cells Correlate with Disease Progression of Chronic HIV-1 Infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    CD4+CD25+ Regulatory T cells (Treg) have been found to down-regulate immune activation in HIV-1 infection. However, whether the depletion of Treg benefits to the disease status of HIV infection remains undefined. To address this issue, we enumerated the Treg absolute counts and frequency in 75 antiviral-na(i)ve HIV-1-infected individuals in this study. It was found that HIV-infected patients displayed a significant decline in Treg absolute counts but a significant increase in Treg frequency. In addition, with disease progression indicated by CD4 T-cell absolute counts, circulating Treg frequency gradually increased; while Treg absolute counts were gradually decreased, suggesting that the alteration of Treg number closely correlated with disease progression in HIV infection.Functional analysis further showed that Treg efficiently inhibit both CD4 and CD8 T cell proliferation in vitro. Thus, our findings indicates that Treg actively participate in pathogenesis of chronic HIV infection,influencing the disease progression.

  12. Chinese Drugs That Invigorate Spleen to Remove Dampness and Activate Blood Circulation to Eliminate Turbid for Retarding Progression of Chronic Renal Failure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effect of Chinese drugs (CD) that invigorate Spleen to remove Dampness and activate the blood circulation to eliminate Turbid for retarding progression of chronic renal failure (CRF). Methods: Thirty-nine patients with CRF were divided into two groups at random: the 18 patients in group A (the control group) were treated with low protein diet and controlling blood pressure and 21 patients in group B (the treatment group) were treated similarly with that of the control group and additional CD. Levels of serous creatinine (SCr), blood urea nitrogen (BUN), blood albumin (Alb), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and hemoglobin (Hb) were checked every two months and the rate of progression of CRF was estimated by slope of the creatinine reciprocal (1/SCr) with time (months). Results: Levels of SCr and BUN in group B were lower and HDL higher than those in group A significantly, P<0.05. Mean slopes of the creatinine reciprocal with time in the two groups were markedly different, P<0.01. Conclusion: Additional CD treatment based upon the low protein diet and controlling blood pressure could retard the rate of progression of CRF evidently.

  13. Progress in Space Weather Modeling and Observations Needed to Improve the Operational NAIRAS Model Aircraft Radiation Exposure Predictions

    Science.gov (United States)

    Mertens, C. J.; Kress, B. T.; Wiltberger, M. J.; Tobiska, W.; Xu, X.

    2011-12-01

    The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a prototype operational model for predicting commercial aircraft radiation exposure from galactic and solar cosmic rays. NAIRAS predictions are currently streaming live from the project's public website, and the exposure rate nowcast is also available on the SpaceWx smartphone app for iPhone, IPad, and Android. Cosmic rays are the primary source of human exposure to high linear energy transfer radiation at aircraft altitudes, which increases the risk of cancer and other adverse health effects. Thus, the NAIRAS model addresses an important national need with broad societal, public health and economic benefits. The processes responsible for the variability in the solar wind, interplanetary magnetic field, solar energetic particle spectrum, and the dynamical response of the magnetosphere to these space environment inputs, strongly influence the composition and energy distribution of the atmospheric ionizing radiation field. During the development of the NAIRAS model, new science questions were identified that must be addressed in order to obtain a more reliable and robust operational model of atmospheric radiation exposure. Addressing these science questions require improvements in both space weather modeling and observations. The focus of this talk is to present these science questions, the proposed methodologies for addressing these science questions, and the anticipated improvements to the operational predictions of atmospheric radiation exposure. The overarching goal of this work is to provide a decision support tool for the aviation industry that will enable an optimal balance to be achieved between minimizing health risks to passengers and aircrew while simultaneously minimizing costs to the airline companies.

  14. The effect of chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA radiofrequency radiation on the incidence of spontaneous tumors in rats.

    Science.gov (United States)

    La Regina, Marie; Moros, Eduardo G; Pickard, William F; Straube, William L; Baty, Jack; Roti Roti, Joseph L

    2003-08-01

    This study was designed to determine whether chronic exposure to radiofrequency (RF) radiation from cellular phones increased the incidence of spontaneous tumors in F344 rats. Eighty male and 80 female rats were randomly placed in each of three irradiation groups. The sham group received no irradiation; the Frequency Division Multiple Access (FDMA) group was exposed to 835.62 MHz FDMA RF radiation; and the Code Division Multiple Access (CDMA) group was exposed to 847.74 MHz CDMA RF radiation. Rats were irradiated 4 h per day, 5 days per week over 2 years. The nominal time-averaged specific absorption rate (SAR) in the brain for the irradiated animals was 0.85 +/- 0.34 W/kg (mean +/- SD) per time-averaged watt of antenna power. Antennas were driven with a time-averaged power of 1.50 +/- 0.25 W (range). That is, the nominal time-averaged brain SAR was 1.3 +/- 0.5 W/kg (mean +/- SD). This number was an average from several measurement locations inside the brain, and it takes into account changes in animal weight and head position during irradiation. All major organs were evaluated grossly and histologically. The number of tumors, tumor types and incidence of hyperplasia for each organ were recorded. There were no significant differences among final body weights or survival days for either males or females in any group. No significant differences were found between treated and sham-exposed animals for any tumor in any organ. We conclude that chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA RF radiation had no significant effect on the incidence of spontaneous tumors in F344 rats.

  15. Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

    Science.gov (United States)

    Portas, M; Mansilla, E; Drago, H; Dubner, D; Radl, A; Coppola, A; Di Giorgio, M

    2016-09-01

    Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy. © World Health Organisation 2016. All rights reserved. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.

  16. Gene-environment interaction in progression of AMD: the CFH gene, smoking and exposure to chronic infection.

    Science.gov (United States)

    Baird, Paul N; Robman, Luba D; Richardson, Andrea J; Dimitrov, Peter N; Tikellis, Gabriella; McCarty, Catherine A; Guymer, Robyn H

    2008-05-01

    A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 individuals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and individuals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28, 95% CI 1.26-4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment-interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.

  17. Murine Models for Trypanosoma brucei gambiense disease progression--from silent to chronic infections and early brain tropism.

    Directory of Open Access Journals (Sweden)

    Christiane Giroud

    Full Text Available Human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates.T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS, a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms

  18. Radiation Risk from Chronic Low Dose-Rate Radiation Exposures: The Role of Life-Time Animal Studies - Workshop October 2005

    Energy Technology Data Exchange (ETDEWEB)

    Gayle Woloschak

    2009-12-16

    As a part of Radiation research conference, a workshop was held on life-long exposure studies conducted in the course of irradiation experiements done at Argonne National Laboratory between 1952-1992. A recent review article documents many of the issues discussed at that workshop.

  19. Radiative neutron capture as a counting technique at pulsed spallation neutron sources: a review of current progress

    Science.gov (United States)

    Schooneveld, E. M.; Pietropaolo, A.; Andreani, C.; Perelli Cippo, E.; Rhodes, N. J.; Senesi, R.; Tardocchi, M.; Gorini, G.

    2016-09-01

    Neutron scattering techniques are attracting an increasing interest from scientists in various research fields, ranging from physics and chemistry to biology and archaeometry. The success of these neutron scattering applications is stimulated by the development of higher performance instrumentation. The development of new techniques and concepts, including radiative capture based neutron detection, is therefore a key issue to be addressed. Radiative capture based neutron detectors utilize the emission of prompt gamma rays after neutron absorption in a suitable isotope and the detection of those gammas by a photon counter. They can be used as simple counters in the thermal region and (simultaneously) as energy selector and counters for neutrons in the eV energy region. Several years of extensive development have made eV neutron spectrometers operating in the so-called resonance detector spectrometer (RDS) configuration outperform their conventional counterparts. In fact, the VESUVIO spectrometer, a flagship instrument at ISIS serving a continuous user programme for eV inelastic neutron spectroscopy measurements, is operating in the RDS configuration since 2007. In this review, we discuss the physical mechanism underlying the RDS configuration and the development of associated instrumentation. A few successful neutron scattering experiments that utilize the radiative capture counting techniques will be presented together with the potential of this technique for thermal neutron diffraction measurements. We also outline possible improvements and future perspectives for radiative capture based neutron detectors in neutron scattering application at pulsed neutron sources.

  20. RADIATION-INDUCED PROGRESSIVE DECREASINGIN THE EXPRESSION OF REVERSE TRANSCRIPTASE GENE OF hEST2 AND TELOMERASE ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    朱涵能; 熊思东; 程文英

    2001-01-01

    Objectites. In order to identify the relationship between telomerase and the biological effect of radiation injury, and investigate the role of human telomerase catalytic subunit gene (hEST2) reverse tranacriptase(RT) seg-ment in the expression of telomerase activity. Methods. Tumor FIeLa cells, KB cells and A431 cells were employed to measure the change in telomeraseactivity after 60Co-ray irradiation at RNA level and protein level. Quantitative PCR and Northern blotting wereused to determine the expression of bEST2 RT segment that encodes seven motifs of the human telomeres, a PCR-besed telomeric repeat amplification protocol (TRAP)was used to assay telomerase activity after exposure toradiation. Results. Both of telomerase activity and the expression hEST2 RT segment were decreased with increasingdosage of radiation. In addition, testing the expression of motifs domain is similar to the measurement of telomerase activity. Conclusion. The detection of the hEST2 BT segment by Northern blotting and quantitative PCR are new methods for testing Uflomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer ceils after irradiation.

  1. Combination of low body mass index and serum albumin level is associated with chronic kidney disease progression: the chronic kidney disease-research of outcomes in treatment and epidemiology (CKD-ROUTE) study.

    Science.gov (United States)

    Kikuchi, Hiroaki; Kanda, Eiichiro; Mandai, Shintaro; Akazawa, Masanobu; Iimori, Soichiro; Oi, Katsuyuki; Naito, Shotaro; Noda, Yumi; Toda, Takayuki; Tamura, Teiichi; Sasaki, Sei; Sohara, Eisei; Okado, Tomokazu; Rai, Tatemitsu; Uchida, Shinichi

    2017-02-01

    The relationship between protein-energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression. The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2-5) enrolled from 2010 to 2011. Patients were categorized into four groups according to their serum albumin levels and BMI: group 1, low serum albumin level (BMI (BMI; group 3, low serum albumin level and high BMI (≥23.5 kg/m(2)); and group 4, high serum albumin level and high BMI. The primary outcome was a 30 % decline in estimated glomerular filtration rate (eGFR) or start of dialysis within 2 years. The secondary outcome was an annual GFR decline (mL/min/1.73 m(2)/year). Logistic regression analysis adjusted for baseline characteristics (reference, group 4) showed that only group 1 was associated with a significant risk of CKD progression, with adjusted odds ratio of 3.51 [95 % confidence interval (CI) (1.63, 7.56)]. A multivariate linear regression analysis adjusted for baseline characteristics showed a significant difference in annual eGFR decline between groups 1 and 4 [coefficients β (standard error) -2.62 (0.75), p = 0.001]. This study suggests that combined effects of low BMI (<23.5 kg/m(2)) and serum albumin level (<4 g/dL) are associated with CKD progression.

  2. Hepatocyte expression of minichromosome maintenance protein-2 predicts fibrosis progression after transplantation for chronic hepatitis C virus: a pilot study.

    Science.gov (United States)

    Marshall, Aileen; Rushbrook, Simon; Morris, Lesley S; Scott, Ian S; Vowler, Sarah L; Davies, Susan E; Coleman, Nicholas; Alexander, Graeme

    2005-04-01

    Although graft infection with hepatitis C virus (HCV) occurs in virtually all patients transplanted for HCV-related liver disease, the outcome ranges from minimal disease to the rapid development of cirrhosis. Induction of hepatocyte cell cycle entry followed by inhibition of cell cycle progression has been proposed as a potential mechanism whereby HCV may cause hepatocyte dysfunction and may promote fibrogenesis. The aim of this study was to assess whether early hepatocyte cell cycle entry might predict subsequent fibrosis progression in patients with graft HCV infection after liver transplantation. Liver biopsies from 21 liver transplant recipients diagnostic of graft HCV infection but before development of significant fibrosis were studied. Patients were classed as nonprogressors, intermediate progressors, or rapid progressors according to the rate of fibrosis progression calculated from the most recent biopsy. Minichromosome maintenance protein 2 (Mcm-2), a highly sensitive and specific marker of cell cycle entry, and cyclin-dependent kinase inhibitor p21 were detected by immunohistochemistry. Hepatocyte Mcm-2 expression increased significantly according to rate of fibrosis. For nonprogressors, the median percentage of positive hepatocytes was 5.3% (range, 0.92%-11.2%) compared with 20.7% (4.6%-43.7%) in intermediate progressors and 23.7% (11.6%-55.2%) in rapid progressors (P = 0.002). By contrast, there was no evidence of a difference in hepatocyte p21 expression. Median values and ranges were 3.4% (range, 1.1%-30%), 13.3% (range, 1.4%-42.3%), and 11.8% (range, 7.6%-52.3%) for nonprogressors, intermediate progressors, and rapid progressors, respectively (P = 0.11). In conclusion, hepatocyte cell cycle entry may be important in the pathogenesis of posttransplant HCV hepatitis. Early assessment of hepatocyte Mcm-2 expression could help identify patients at high risk for progressive fibrosis before it occurs.

  3. Is argon plasma coagulation an effective and safe treatment option for patients with chronic radiation proctitis after high doses of radiotherapy?

    Directory of Open Access Journals (Sweden)

    Eduardo Hortelano

    Full Text Available Introduction: In severe cases refractory to medical treatment, APC appears to be the preferred alternative to control persistent rectal bleeding of patients with chronic radiation proctitis. Although successful outcomes have been demonstrated in patients previously treated with moderate doses of radiotherapy, there is reluctance towards its indication due to the concern of severe adverse events in patients treated with high doses of radiation. Objectives: The aim of this study was to assess the efficacy and toxicity of APC in the management of bleeding radiation-induced proctitis in patients treated with high doses of radiation for prostate cancer. Methods and materials: Data from 30 patients were treated with APC due to chronic radiation proctitis, were reviewed retrospectively. All cases had prostate cancer and 9 of them (30 % underwent previous radical prostatectomy. The median dose of conformal 3D External Beam Radiotherapy (EBRT delivered was 74 Gy (range 46-76. Median rectal D1cc and D2cc was 72.5 and 72.4 Gy respectively. Median rectal V70, V60 and V40 was 12, 39.5 and 80 %. Cardiovascular and digestive disease, diabetes, smoking behaviour, lowest haemoglobin and transfusion requirements were recorded. Indications for treatment with APC were anemia and persistent bleeding despite medical treatment. Argon gas flow was set at 1.8 l/min with an electrical power setting of 50 W. Results: Median age of all patients was 69.6 years. The median lowest haemoglobin level was 9.6 g/dL. Median time between completion of radiotherapy and first session of APC was 13 months. Ninety-four therapeutic sessions were performed (median 3 sessions. Median time follow-up was 14.5 months (range 2-61. Complete response with resolved rectal bleeding was achieved in 23 patients (77 %, partial response in 5 (16 % and no control in 2 (6 %. No patients required transfusion following therapy. Two patients developed long-term (> 6 weeks grade 2 rectal ulceration and

  4. 慢性盆腔痛的研究进展%Progress in research on chronic pelvic pain

    Institute of Scientific and Technical Information of China (English)

    李晓宏; 高崇荣; 杨承祥; 李光仪

    2008-01-01

    慢性盆腔痛(chronic pelvic pain,CPP)是疼痛科和妇科门诊的常见疾病,因其病因复杂,其中有妇科方面的因素,也有非妇科方面的原因,所以诊断异常棘手,目前诊断的金标准是腹腔镜检查;CPP的保守治疗效果欠佳,临床治疗主要是以手术为主,如腹腔镜下骶前神经的切除,但现提倡多学科的治疗,如介入治疗的上腹下丛神经毁损,也能取得很好的效果.%Chronic pelvic pain (CCP) is a common pain syndrome which has complex causes including gynecologic and nongynecologic factors. A exact diagnosis is difficult to be delivered. The current gold standard of diagnostic examination is abdominoscopy. Lacking ideal effect with conventional therapy, the main therapeutic method adopted is surgical intervention, such as laparoscopic presacral neureetomy. Muhidisciplinary managements, for example, superior hypogastric plexus neurolysis using interventional therapy,are expected to be effective.

  5. Effect of radiation-sensitive mutations and mutagens/carcinogens on bacterial recombination and mutagenesis. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Matney, T.S.

    1978-01-01

    Progress is reported on effects of temperature sensitive DNA-initiation mutation in E. coli K-12 mutants; the use of Bacillus subtilis transforming system as an in vitro mutagenesis system; characteristics of the E. coli lysogen used to test the permeability to polycyclic aromatic hydrocarbons; and the genetic toxicology of gentian violet. (PCS)

  6. Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia.

    Science.gov (United States)

    Mulligan, Stephen P; Karlsson, Karin; Strömberg, Mats; Jønsson, Viggo; Gill, Devinder; Hammerström, Jens; Hertzberg, Mark; McLennan, Roger; Uggla, Bertil; Norman, John; Wallvik, Jonas; Sundström, Gunnel; Johansson, Hemming; Brandberg, Yvonne; Liliemark, Jan; Juliusson, Gunnar

    2014-12-01

    We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

  7. Current perspectives on the contribution of inhaled corticosteroids to an increased risk for diabetes onset and progression in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Herth, Felix J F; Bramlage, Peter; Müller-Wieland, Dirk

    2015-01-01

    Recent studies have suggested that inhaled corticosteroids (ICS) play a role in the development of hyperglycemia and type-2 diabetes in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, this corticosteroid-associated adverse effect remains controversial. Moreover, the pharmacokinetic properties and patient characteristics that might contribute to an increased risk for diabetes upon ICS exposure have not been thoroughly investigated. In the present review, we critically discuss current evidence regarding the relationship between ICS therapy in COPD patients and an increased risk for the incidence and progression of type-2 diabetes. In addition, we address therapeutic conditions, clinical implications, and future perspectives related to this potentially important ICS-associated adverse effect in COPD patients.

  8. Physico-chemical studies of radiation effects in cells. Progress report, November 15, 1980-February 14, 1984

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1983-01-01

    The primary interest is investigating and understanding the chemical mechanisms involved in radiation-induced cellular damage. Most recently the perturbating devices have been metals which increase, in various ways and modes, the radiation sensitivity of several cell types. While the chief cell type has been the bacterial spore, chosen because of its biological inertness and its hardiness, allowing it to survive the unphysiological conditions of the physical chemist and, thus, inquiry into the free radical mechanisms involved very soon after energy absorption, recently vegetative cells have been introduced. A number of metals have been used and practically all of them sensitize - but to varying degrees. Straight biological techniques such as the measurement of cell survival under various conditions in the different cells have been used, as well as parallel experiments in pulse radiolysis to attack the specific leads in a chemical fashion suggested by the biology.

  9. Effect of LET and microdistribution of radiation on the transformation in vitro and in vivo. Comprehensive progress report

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.

    1983-09-01

    Work has involved the following three areas: (1) an investigation of the mechanisms of radiation carcinogenesis by studying the events involved in the process of malignant transformation of mouse 10 T-1/2 cells; (2) an investigation of the effects of promoting agents on radiation-induced transformation in vitro; and (3) an investigation of the induction of transformation by internally emitting radionuclides incorporated into cellular DNA. The latter area has been extended to include studies of mutagenesis by these radionuclides in human lymphoblasts, and molecular measurements of DNA strand breaks. During the past year, research has focused on the first area, as well as on studies of the mutagenic effects of incorporated radionuclides.

  10. 慢性放射性肠炎并发肠梗阻的治疗%Management of chronic radiation enteritis with intestinal obstruction

    Institute of Scientific and Technical Information of China (English)

    周创业; 周振理; 马军宏; 吕鹏

    2011-01-01

    目的:探讨慢性放射性肠炎并发肠梗阻的治疗方法及疗效.方法:回顾分析21例慢性放射性肠炎并发肠梗阻的临床资料,对其进行总结.结果:7例保守治疗的病例中有5例复发,治愈率仅(28.6%,2/7),保守治疗效果不佳.14例手术患者总体疗效满意.10例行肠切除吻合术的患者,治愈率达(90.0%,9/10),可见手术治疗为慢性放射性肠炎并发肠梗阻的最佳方法.1例出现吻合口瘘的患者,再次手术证实为第1次手术切除肠管过少,残留病变肠管所致.结论:慢性放射性肠炎并发肠梗阻的最佳治疗方法为手术治疗,手术方式应尽量行肠切除一期吻合术,手术时应尽量切除全部病变肠管,避免出现吻合口瘘.同时肠造口术或旁路手术也是必要术式,应根据具体情况选择.%AIM: To evaluate the effect of various treatment methods for chronic radiation enteritis with concurrent intestinal obstruction.METHODS: The clinical data for 21 patients with chronic radiation enteritis and intestinal obstruction was retrospectively analyzed.RESULTS: Five of seven patients who received conservative treatment experienced relapse, and the cure rate was only 28.6%. Fourteen patients who underwent surgical treatment (of them ten patients underwent intestinal resection and anastomosis) had satisfactory outcome, and the cure rate was as high as 90.0%. One patient developed intestinal fistula, and re-operation confirmed that it was caused by residual radiation enteritis.CONCLUSION: Surgical treatment is the bestway for treatment of chronic radiation enteritis with intestinal obstruction. All intestinal lesions should be surgically removed to avoid intestinal fistula.

  11. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  12. Retrospective results of radiation therapy of the Eustachian tube in chronic otitis media; Retrospektive Ergebnisse der perkutanen Strahlentherapie der Tuba Eustachii bei chronischer Otitis media

    Energy Technology Data Exchange (ETDEWEB)

    Schultze, J.; Reinke, C.; Kimmig, B. [Klinik fuer Strahlentherapie (Radioonkologie), Universitaetsklinikum Kiel (Germany); Frese, K.A. [Klinik fuer Hals-, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie, Universitaetsklinikum Kiel (Germany)

    2003-01-01

    Background: The treatment results of symptomatic radiation therapy of the Eustachian tube in chronic otitis media had to be evaluated retrospectively. Patients and Methods: Between 1980 and 1997, 66 patients were referred for therapy. The median age was 58 years. In the clinical presentation, all the patients had a hearing impairment, 35 patients complained of pain, 21 had otorrhea. In their history, 20 patients indicated chronic recurrent infections. The complaints lasted for 4.7 years in the median, primary conservative (adstringentia, antibiotics) and surgical treatment (paracentesis, tympanic tubule, tympanoplastic) did not lead to lasting cure. In 40 of 66 patients, finally radiation therapy was done of both Eustachian tubes. With opposed fields and cobalt-60 photons a total dose of 6 Gy at single doses of 1 Gy, three times a week, was applied. Under the causes for exclusion of radiation therapy were non-acceptance of the patients (nine), prior radiation therapies (six) or spontaneous improvement after initial presentation in our department. The treatment results were evaluated by interviews of the patients and regular otorhinolaryngological examinations. Results: There were no side effects noticed. 28 of 40 (70%) patients reported a significant improvement that could be verified by objective otorhinolaryngological examinations. In the group of 26 nonirradiated patients, 22 could be interviewed indicating in 16 cases (72%) that the complaints were unchanged and chronic otitis media was lasting. In a subgroup analysis concerning the duration of otitis media radiation therapy proved more effective in an acute and subacute stadium of disease of up to 5 years duration, while the patients resistant to radiation therapy were entirely in a chronic stage of disease exceeding 5 years duration. (orig.) [German] Hintergrund: Die Behandlungsergebnisse der symptomatischen Radiotherapie bei chronischer Otitis media sollten retrospektiv evaluiert werden. Patienten und

  13. Current situation and progress in limb salvage therapy for chronic osteomyelitis%慢性骨髓炎保肢治疗现状及进展

    Institute of Scientific and Technical Information of China (English)

    王军; 李宗原; 王陶

    2014-01-01

    慢性骨髓炎治疗周期长,效果差,截肢率高,是创伤骨科临床中的难题之一。近年来保肢治疗成为慢性骨髓炎研究的热点,该文综述慢性骨髓炎保肢治疗涉及的病灶清除、骨缺损治疗、软组织覆盖、患肢骨稳定、抗生素治疗以及辅助治疗的现状及进展。%Treatment of chronic osteomyelitis is difficult in the field of orthopaedic trauma surgery, with long therapy course, poor clinical results and high amputation rate. In recent years, limb salvage has gradually become a research hotspot. In this paper, present situation and progress in limb salvage therapy for chronic osteomyelitis were reviewed, involving the aspects of debridement, treatment of bone defect, soft tissue coverage, stabilization of affected bone, antibiotic treatment and adjuvant therapy.

  14. Effect of chronic antioxidant therapy with superoxide dismutase-mimetic drug, tempol, on progression of renal disease in rats with renal mass reduction.

    Science.gov (United States)

    Quiroz, Yasmir; Ferrebuz, Atilio; Vaziri, Nosratola D; Rodriguez-Iturbe, Bernardo

    2009-01-01

    Oxidative stress and inflammation play a major role in the progression of renal damage and antioxidants are potentially useful therapeutic options in chronic renal disease. We investigated if treatment with tempol, a superoxide dismutase mimetic that has beneficial effects in several experimental models of hypertension and acute kidney injury, ameliorates the chronic renal damage resulting in renal mass reduction. Rats with surgical 5/6 nephrectomy were randomly assigned to receive no treatment (CRF group, n = 10) or tempol, 1 mmol/l in the drinking water (CRF-tempol group, n = 10). Sham-operated rats (n = 10) served as controls. All rats were followed for 12 weeks post-nephrectomy. Tempol treatment reduced plasma malondialdehyde (MDA) levels and halved the number of superoxide-positive cells in the remnant kidney; however, the number of hydrogen peroxide-positive cells increased and the overall renal oxidative stress (MDA and nitrotyrosine abundance) and inflammation (interstitial p65 NF-kappaB, macrophage and lymphocyte infiltration) were unchanged. Proteinuria, renal function and glomerular and tubulointerstitial damage in the remnant kidney were similar in the CRF and CRF-tempol groups. In conclusion, tempol administration, at the dose used in these studies, decreased plasma MDA and heightened superoxide dismutation in the kidney, but was incapable of reducing renal oxidative stress or improving renal function or structure in the remnant kidney model.

  15. FTY720 prevents progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease.

    Science.gov (United States)

    Ni, Haifeng; Chen, Junfeng; Pan, Mingming; Zhang, Minghui; Zhang, Jiandong; Chen, Pingsheng; Liu, Bicheng

    2013-12-01

    Recent studies have shown that chronic endothelial dysfunction can impair multiple aspects of renal physiology and, in turn, contribute to renal fibrosis. Sphingosine 1-phosphate (S1P) has been highlighted as an endothelial barrier-stabilizing mediator. The aim of our study was to investigate the effect of FTY720, an S1P analog, on the progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease. Thirty male Sprague-Dawley rats were used in this study. Seven days after surgery, we placed the animals into three groups: sham surgery; 5/6 nephrectomized (Nx) rats; and 5/6Nx + FTY720 (1 mg/kg/day). All of the animals were sacrificed 12 weeks after surgery. We obtained and analyzed blood and kidney tissue samples from all of the groups. Glomerular capillary density and peritubular capillary (PTC) density were determined by CD31 immunostaining. The expression of transforming growth factor beta 1 (TGF-β1), collagen IV, fibronectin, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction and western blotting. The 5/6Nx group exhibited increased blood urea nitrogen and serum creatinine, visible renal histological changes, pro-fibrotic molecule (TGF-β1) and production of extracellular matrix proteins such as collagen IV and fibronectin and decreased glomerular and PTC density, compared to the sham controls (P kidney disease.

  16. The progress of researches on chronic liver disease and intestinal flora%慢性肝病与肠道菌群的研究进展

    Institute of Scientific and Technical Information of China (English)

    秦庆福; 李洪福

    2012-01-01

    肝脏与肠道微生态可谓息息相关,互为影响.慢性肝病患者均存在不同程度的菌群失调,而菌群失调与血内毒素水平升高相关,且可诱发肝性脑病、二重感染的发生.肠道菌群失调促进了慢性肝病并发症的发生、发展,增加了患者的死亡率,且菌群失调与肝功能损害程度成正比.微生态制剂可通过恢复肠道菌群平衡,维持肠道屏障的完整性,抑制产生内毒素的G数量,减少肠氨的产生,辅助治疗慢性肝病.%The liver was closely related to gut mieroflora. Chronic liver disease patients had alteration of intestinal flora , which was associated with increasing endotoxin blood, hepatic encephalopathy, and the occurrence of superinfection. Im-balanced intestinal flora promoted the occurrence and progression of complications of chronic liver disease, increased mortality, and was proportional to the degree of liver dysfunction. Probiotics could restore intestinal flora balance, maintain the integrity of the intestinal barrier, inhibit the amount of G ~ , reduce the production of intestinal ammonia, and aid in the treatment of chronic liver disease.

  17. Investigation of microscopic radiation damage in waste forms using ODNMR and AEM techniques. 1997 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.

    1997-09-01

    'This project seeks to understand the microscopic effects of radiation damage in nuclear waste forms. The authors approach to this challenge encompasses studies in electron microscopy, laser spectroscopy, and computational modeling and simulation. During this first year of the project, efforts have focused on a-decay induced microscopic damage in crystalline orthophosphates (YPO{sub 4} and LuPO{sub 4}) that contain the short-lived a-emitting isotope {sup 244}Cm (t{sub 1/2} = 18.1 y). The samples that they studied were synthesized in 1980 and the initial {sup 244}Cm concentration was {approximately}1%. Studying these materials is of importance to nuclear waste management because of the opportunity to gain insight into accumulated radiation damage and the influence of aging on such damage. These factors are critical to the long-term performance of actual waste forms [1]. Lanthanide orthophosphates, including LuPO{sub 4} and YPO{sub 4}, have been suggested as waste forms for high level nuclear waste [2] and potential hosts for excess weapons plutonium [3,4]. The work is providing insight into the characteristics of these previously known radiation-resistant materials. They have observed loss of crystallinity (partial amorphization) as a direct consequence of prolonged exposure to intense alpha radiolysis in these materials. More importantly, the observation of microscopic cavities in these aged materials provides evidence of significant chemical decomposition that may be difficult to detect in the earlier stages of radiation damage. The preliminary results show that, in characterizing crystalline compounds as high level nuclear waste forms, chemical decomposition effects may be more important than lattice amorphization which has been the focus of many previous studies. More extensive studies, including in-situ analysis of the dynamics of thermal annealing of self-radiation induced amorphization and cavity formation, will be conducted on these aged {sup 244}Cm

  18. Induction of Tet3-dependent Epigenetic Remodeling by Low-dose Hydralazine Attenuates Progression of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Björn Tampe

    2015-01-01

    Retrospective analysis of patients with hypertensive nephrosclerosis revealed that circulating methylated RASAL1 promoter DNA fragments in peripheral blood decrease with Dihydralazine treatment in patients with hypertensive nephrosclerosis, and provided evidence that low-dose Dihydralazine delays decline of excretory kidney function, whereas Dihydralazine at standard doses had no protective effect. We demonstrate that the protective effect of Dihydralazine is due to induction of endogenous Tet3/Tdg-mediated DNA-de-methylation activity reversing aberrant promoter CpG island methylation, while HIF1α induction at standard doses counterbalances its protective activity. We conclude that RASAL1 promoter methylation is a therapeutic target and a biomarker of renal fibrosis. Our study suggests that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration.

  19. Evaluation of the impact of the urinary symptoms on quality of life of patients with painful bladder syndrome/chronic pelvic pain and radiation cystitis: EURCIS study.

    Science.gov (United States)

    Rapariz-González, M; Castro-Díaz, D; Mejía-Rendón, D

    2014-05-01

    To evaluate the impact of urinary symptoms of Painful Bladder/Pelvic Pain Syndrome and Radiation Cystitis (PBCPPS) on the Quality of Life, and self-esteem of the patient. An observational, multicenter, epidemiological and cross-sectional study was performed on patients with Painful Bladder/Chronic Pelvic Pain Syndrome and Radiation Cystitis. Data was recorded on severity of urinary symptoms and QoL impairment using the PUF Score. The patients evaluated the QoL deterioration grade through the King's Health Questionnaire (KHQ), and the level of their anxiety and self-esteem with the Goldberg's Anxiety Scale (GAS) and Rosenberg's Self-Esteem Scale (RSES), respectively. Post-hoc comparisons were performed between the results of the KHQ of this study and a sample of patients with urinary incontinence (UI). Results on RSES were analyzed with data from the general population and from patients with erectile dysfunction. A total of 530 cases, mostly female patients, who had been diagnosed with PBCPPS, were analyzed. High levels of deterioration in QoL were described: KHQ scores were significantly higher when compared with patients with UI (P<.01). Involvement of self-esteem was higher in patients with RC and men, who obtained scores similar to those of patients with erectile dysfunction. Patients with Painful Bladder Syndrome/Chronic Pelvic Pain Syndrome and Radiation Cystitis present high levels of anxiety, and significant reductions in both quality of life and self-esteem. Especially for men, this affectation is similar to that caused by erectile dysfunction. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  20. H. pylori infection increases gastric mucosal COX2 and mTOR expression in chronic gastritis: Implications for cancer progression?

    Science.gov (United States)

    Badary, Dalia M; Rahma, Mohammed Zakaria Ali Abu; Ashmawy, Ahmed M; Hafez, Mohamed Z

    2017-09-01

    Helicobacter Pylori is a Gram-negative bacterium that infects the human stomach and plays an important role in the pathogenesis of chronic gastritis. H. pylori associated chronic gastritis affects various molecular markers related to gastric cancer development. The aim of this study to assess the effect of H. pylori infection on gastric mucosa and to explore its role in gastric carcinogenesis via COX2 and mTOR mucosal expression. This study comprised archival blocks from 60 dyspeptic patients who underwent gastric endoscopic biopsies for histopathological examination. The blocks were cut at 4 μm thicknesses, stained with hematoxylin and eosin to score, using updated Sydney system, and subjected to Giemsa stain to assess H. pylori infection. Then, immunohistochemical method was carried out to determine the expression of COX2 and mTOR. Increased H. pylori colonization was significantly correlated with increased severity of inflammation, activity, atrophy, intestinal metaplasia, and the presence of high-grade dysplasia. Also, studied molecular markers were significantly associated with increased H. pylori colonization and presence of severe metaplasia, atrophy, and dysplasia. These findings suggest that there is a positive feedback loop between H. pylori infection and the pathogenesis of gastric mucosal changes. Also, mTOR and COX2 over expression cause premalignant changes and subsequent tumor occurrence. This may help in providing innovative approaches for the detection of patients-with a higher chance of cancer development, and in trying to introduce effective therapy preventing tumor occurrence, or even using these molecular markers as potential targets for tumors treatment strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Chronic granulomatous disease

    Science.gov (United States)

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... In chronic granulomatous disease (CGD), immune system cells called phagocytes are unable to kill some types of bacteria and ...

  2. Is argon plasma coagulation an effective and safe treatment option for patients with chronic radiation proctitis after high doses of radiotherapy?

    Science.gov (United States)

    Hortelano, Eduardo; Gómez-Iturriaga, Alfonso; Ortiz-de-Zárate, Roberto; Zaballa, Manuel; Barturen, Ángel; Casquero, Francisco; San-Miguel, Íñigo; Carvajal, Carvajal; Cacicedo, Jon; Del-Hoyo, Olga; Lupiani, Javier; Pérez, Fernando; Bilbao, Pedro

    2014-03-01

    In severe cases refractory to medical treatment, APC appears to be the preferred alternative to control persistent rectal bleeding of patients with chronic radiation proctitis. Although successful outcomes have been demonstrated in patients previously treated with moderate doses of radiotherapy, there is reluctance towards its indication due to the concern of severe adverse events in patients treated with high doses of radiation. The aim of this study was to assess the efficacy and toxicity of APC in the management of bleeding radiationinduced proctitis in patients treated with high doses of radiation for prostate cancer. Data from 30 patients were treated with APC due to chronic radiation proctitis, were reviewed retrospectively. All cases had prostate cancer and 9 of them (30 %) underwent previous radical prostatectomy. The median dose of conformal 3D External Beam Radiotherapy (EBRT) delivered was 74 Gy (range 46-76). Median rectal D1cc and D2cc was 72.5 and 72.4 Gy respectively. Median rectal V70, V60 and V40 was 12, 39.5 and 80 %. Cardiovascular and digestive disease, diabetes, smoking behaviour, lowest haemoglobin and transfusion requirements were recorded. Indications for treatment with APC were anemia and persistent bleeding despite medical treatment. Argon gas flow was set at 1.8 l/min with an electrical power setting of 50 W. Median age of all patients was 69.6 years. The median lowest haemoglobin level was 9.6 g/dL. Median time between completion of radiotherapy and first session of APC was 13 months. Ninety-four therapeutic sessions were performed (median 3 sessions). Median time follow-up was 14.5 months (range 2-61). Complete response with resolved rectal bleeding was achieved in 23 patients (77 %), partial response in 5 (16 %) and no control in 2 (6 %). No patients required transfusion following therapy. Two patients developed long-term (> 6 weeks) grade 2 rectal ulceration and grade 2 rectal incontinence, respectively. The argon plasma coagulation

  3. Circulating sCD138 and Some Angiogenesis-Involved Cytokines Help to Anticipate the Disease Progression of Early-Stage B-Cell Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Syndecan-1 (CD138 is a transmembrane heparin sulfate proteoglycan expressed on distinct stages of differentiation of B-lymphoid cells. Its prognostic value in B-cell chronic lymphocytic leukemia (B-CLL has not been evaluated so far. The serum concentration of sCD138 and some angiogenesis-involved cytokines: vascular endothelial growth factor (VEGF, basis fibroblast growth factor (bFGF, and endostatin were studied in 52 previously untreated patients with B-CLL. We found that bFGF and sCD138 levels were significantly higher in B-CLL patients than in controls. In patients with sCD138 level or endostatin level below the median value the lymphocyte count was higher than in patients with serum level of those cytokines above the median value. In patients with progressive disease bFGF level was significantly higher and sCD138 level significantly lower than in patients with stable one. Moreover, high sCD138 level was associated with longer lymphocyte doubling-free survival, and, on the limit of statistical significance, a high endostatin level was associated with shorter progression-free survival. We conclude that serum sCD138 level is increased in early stage B-CLL patients and may have a positive prognostic value as to the dynamics of the disease.

  4. Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis

    Directory of Open Access Journals (Sweden)

    Sandra Cascio

    2016-10-01

    Full Text Available Altered glycosylation of mucin 1 (MUC1 on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target for cancer immunotherapy. The importance of altered MUC1 glycosylation extends also to its role as a promoter of chronic inflammatory conditions that lead to malignant transformation and cancer progression. We review here what is known about the role of specific cancer-associated glycans on MUC1 in protein-protein interactions and intracellular signaling in cancer cells and in their adhesion to each other and the tumor stroma. The tumor form of MUC1 also creates a different landscape of inflammatory cells in the tumor microenvironment by controlling the recruitment of inflammatory cells, establishing specific interactions with dendritic cells (DCs and macrophages, and facilitating tumor escape from the immune system. Through multiple types of short glycans simultaneously present in tumors, MUC1 acquires multiple oncogenic properties that control tumor development, progression, and metastasis at different steps of the process of carcinogenesis.

  5. Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia.

    Science.gov (United States)

    Kongtim, Piyanuch; Popat, Uday; Jimenez, Antonio; Gaballa, Sameh; El Fakih, Riad; Rondon, Gabriela; Chen, Julianne; Bueso-Ramos, Carlos; Borthakur, Gautam; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Kantarjian, Hagop; Alousi, Amin; Hosing, Chitra; Anderlini, Paolo; Khouri, Issa F; Kebriaei, Partow; Andersson, Borje S; Oran, Betul; Rezvani, Katayoun; Marin, David; Shpall, Elizabeth J; Champlin, Richard E; Ciurea, Stefan O

    2016-01-01

    The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant (allo-SCT) at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival (PFS). The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; P = .03), whereas treatment-related mortality at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; P = .84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; P = .04). Our data support the use of hypomethylating agents before allo-SCT for patients with CMML to achieve morphologic remission and improve PFS of these patients. Future studies are needed to confirm these findings.

  6. Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Yanling Zhang

    Full Text Available Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2 leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally nephrectomised rats, a model of progressive chronic kidney disease (CKD that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.

  7. Treinamento resistido progressivo nas doenças musculoesqueléticas crônicas Progressive resistance training in chronic musculoskeletal disorders

    Directory of Open Access Journals (Sweden)

    Renata Trajano Jorge

    2009-12-01

    physical exercises in physical therapy, besides optimizing the results of the treatment. OBJECTIVE: To review studies that used progressive resistance training in chronic musculoskeletal diseases and to demonstrate the importance of including this type of training in the rehabilitation of those diseases. SOURCE OF THE DATA: Pubmed, Medline, and Lilacs databases were reviewed without restrictions of date and/or language. REVIEW: Due to the countless benefits attributed to this treatment modality, the importance of exercises in physical therapy has been well documented. Despite the proven efficacy, high-intensity exercises are not routinely prescribed, and this prescription is usually not standardized, which does not allow a consensus on the type of strengthening used, as well as load calculation and progression. Progressive resistance training implies the gradual increase in load during the training period. The number of repetitions that each individual can complete depends on the calculation of the maximal repetition. CONCLUSION: Based on the findings of this review, the use of progressive resistance training to complement traditional exercises used in rehabilitation of chronic musculoskeletal diseases is recommended in order to standardize treatment protocols, with adequate control of individual load, and to optimize training results. However, it should be emphasized that further studies are necessary for more reliable conclusions.

  8. The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

    Science.gov (United States)

    Blumenfeld, P; Pfeffer, R M; Symon, Z; Den, R B; Dicker, A P; Raben, D; Lawrence, Y R

    2014-01-01

    Background: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT–drug development programmes before patent expiration. Methods: We identified novel drug–radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: date the initial phase I trial with/without RT was opened/published, date of the published positive phase III trials, and patent expiration dates. Lag time was defined as the interval between opening of the phase I trial without RT and the opening of the phase I with RT. Linear regression was used to model how the lag time has changed over time. Results: The median lag time was 6 years. The initial phase I trial with RT was typically published 2 years after the first published positive phase III trial and 11 years before patent expiration. Using a best-fit linear model, lag time decreased from 10 years for phase I trials published in 1990 to 5 years in 2005 (slope significantly non-zero, P<0.001). Conclusions: Clinical drug development with RT commences late in the life cycle of anti-cancer agents. Taking into account the additional time required for late-phase clinical trials, the delay in initiating clinical testing of drug–RT combinations discourages drug companies from further pursuing RT-based development. Encouragingly, lag time appears to be decreasing. Further reduction in lag time may accelerate RT-based drug development, potentially improving patient outcomes. PMID:25117813

  9. Measuring radiation damage dynamics by pulsed ion beam irradiation. 2015 Annual Progress Report for DOE/NE/NEET

    Energy Technology Data Exchange (ETDEWEB)

    Kucheyev, S. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-03-07

    The major goal of this project is to develop and demonstrate a novel experimental approach to access the dynamic regime of radiation damage formation processes in nuclear materials. In particular, the project exploits a pulsed-ion-beam method in order to gain insight into defect interaction dynamics by measuring effective defect interaction time constants and defect diffusion lengths. For Year 2, this project had the following two major milestones: (i) measurement of the temperature dependence of defect dynamics in SiC and (ii) the evaluation of the robustness of the pulsed beam method from studies of the defect generation rate. As we describe below, both of these milestones have been met.

  10. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    Science.gov (United States)

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  11. Histone 3.3 Participates in a Self-Sustaining Cascade of Apoptosis That Contributes to the Progression of Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Barrero, Carlos A.; Perez-Leal, Oscar; Aksoy, Mark; Moncada, Camilo; Ji, Rong; Lopez, Yolanda; Mallilankaraman, Karthik; Madesh, Muniswamy; Criner, Gerard J.; Kelsen, Steven G.

    2013-01-01

    Rationale: Shifts in the gene expression of nuclear protein in chronic obstructive pulmonary disease (COPD), a progressive disease that is characterized by extensive lung inflammation and apoptosis, are common; however, the extent of the elevation of the core histones, which are the major components of nuclear proteins and their consequences in COPD, has not been characterized, which is important because extracellular histones are cytotoxic to endothelial and airway epithelial cells. Objectives: To investigate the role of extracellular histones in COPD disease progression. Methods: We analyzed the nuclear lung proteomes of ex-smokers with and without the disease. Further studies on the consequences of H3.3 were also performed. Measurements and Main Results: A striking finding was a COPD-specific eightfold increase of hyperacetylated histone H3.3. The hyperacetylation renders H3.3 resistant to proteasomal degradation despite ubiquitination; when combined with the reduction in proteasome activity that is known for COPD, this resistance helps account for the increased levels of H3.3. Using anti-H3 antibodies, we found H3.3 in the airway lumen, alveolar fluid, and plasma of COPD samples. H3.3 was cytotoxic to lung structural cells via a mechanism that involves the perturbation of Ca2+ homeostasis and mitochondrial toxicity. We used the primary human airway epithelial cells and found that the antibodies to either the C or N terminus of H3 could partially reverse H3.3 toxicity. Conclusions: Our data indicate that there is an uncontrolled positive feedback loop in which the damaged cells release acetylated H3.3, which causes more damage, adds H3.3 release, and contributes toward the disease progression. PMID:23924319

  12. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors

    Science.gov (United States)

    Bang, Ji-Yeon; Kim, Seon-Ok; Kim, Sae-Gyul; Song, Jun-Gol; Hwang, Gyu Sam

    2017-01-01

    Abstract Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors. The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM). The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16–32.77), age (OR, 1.02; 95% CI, 1.00–1.04; P PSM, the risk of progression to CKD was higher in KT donors than in healthy nondonors (HR, 58.4; 95% CI, 34.2–99.8; P < 0.001). Donor nephrectomy is associated with PRKF and progression to CKD. Cys-C is a useful early marker for detecting PRKF and CKD. PMID:28151912

  13. Rapid progression of band-shaped keratopathy with early central localisation in a patient on chronic dialytic treatment.

    Science.gov (United States)

    Klaassen-Broekema, N; Van Bijsterveld, O P

    1994-01-01

    This clinical study reports on an unusual start of a band-shaped keratopathy in a patient with diabetic nephropathy on dialytic treatment. The earliest corneal manifestations were centrally located small greyish-white disc-shaped lesions evenly distributed in the interpalpebral area in the left eye. Later a typical peripheral band-shaped keratopathy developed. In the course of the observation period the peripheral keratopathy rapidly spread towards the centre, finally resulting in a complete band-shaped keratopathy in which only the most central original disc-shaped lesions could be identified. Serum calcium and phosphorus concentrations were markedly elevated at the time of the progression of the band-shaped keratopathy but no tertiary hyperparathyroidism was present.

  14. Plasma insulin-like growth factor I as predictor of progression and all cause mortality in chronic heart failure

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Kistorp, Caroline; Raymond, Ilan

    2009-01-01

    OBJECTIVES: Insulin-like growth factor I (IGF-I) is an anabolic growth factor that seems to increase cardiac contractility. Reduced levels of IGF-I may be implicated in progression of CHF. The objective was to compare plasma IGF-I in CHF patients with healthy controls, and to examine......, renal function and LVEF) IGF-I levels did not influence the overall mortality risk or the admission rate to hospital, hazard ratio (HR) (95% confidence intervals) 1.05 (0.75-1.47) (P=0.77) and 1.00 (0.80-1.26) (P=0.96), respectively per each SD increase in log IGF-I levels. CONCLUSIONS: IGF-I levels...

  15. Technical progress report: Completion of spectral rotating shadowband radiometers and analysis of atmospheric radiation measurement spectral shortwave data

    Energy Technology Data Exchange (ETDEWEB)

    Michalsky, J.; Harrison, L. [State Univ. of New York, Albany, NY (United States)

    1996-04-01

    Our goal in the Atmospheric Radiation Measurement (ARM) Program is the improvement of radiation models used in general circulation models (GCMs), especially in the shortwave, (1) by providing improved shortwave radiometric measurements for the testing of models and (2) by developing methods for retrieving climatologically sensitive parameters that serve as input to shortwave and longwave models. At the Atmospheric Sciences Research Center (ASRC) in Albany, New York, we are acquiring downwelling direct and diffuse spectral irradiance, at six wavelengths, plus downwelling broadband longwave, and upwelling and downwelling broadband shortwave irradiances that we combine with National Weather Service surface and upper air data from the Albany airport as a test data set for ARM modelers. We have also developed algorithms to improve shortwave measurements made at the Southern Great Plains (SGP) ARM site by standard thermopile instruments and by the multifilter rotating shadowband radiometer (MFRSR) based on these Albany data sets. Much time has been spent developing techniques to retrieve column aerosol, water vapor, and ozone from the direct beam spectral measurements of the MFRSR. Additionally, we have had success in calculating shortwave surface albedo and aerosol optical depth from the ratio of direct to diffuse spectral reflectance.

  16. Radiation-dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1981-June 1982

    Energy Technology Data Exchange (ETDEWEB)

    Mewhinney, J.A.

    1983-06-01

    The objective was to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research. The first paper details development of a method for determination of specific surface area of small samples of mixed oxide or pure PuO/sub 2/ particles. The second paper details the extension of the biomathematical model previously used to describe retention, distribution and excretion of Pu from these mixed oxide aerosols to include a description of Am and U components of these aerosols. The third paper summarizes the biological responses observed in radiation dose pattern studies in which dogs, monkeys and rate received inhalation exposures to either 750/sup 0/C heat treated UO/sub 2/ + PuO/sub 2/, 1750/sup 0/C heat-treated (U,Pu)O/sub 2/ or 850/sup 0/C heat-treated pure PuO/sub 2/. The fourth paper described dose-response studies in which rats were exposed to (U,Pu)O/sub 2/ or pure PuO/sub 2/. This paper updates earlier reports and summarizes the status of animals through approximately 650 days after inhalation.

  17. Radiation-dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1981-June 1982

    Energy Technology Data Exchange (ETDEWEB)

    Mewhinney, J.A.

    1983-06-01

    The objective was to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research. The first paper details development of a method for determination of specific surface area of small samples of mixed oxide or pure PuO/sub 2/ particles. The second paper details the extension of the biomathematical model previously used to describe retention, distribution and excretion of Pu from these mixed oxide aerosols to include a description of Am and U components of these aerosols. The third paper summarizes the biological responses observed in radiation dose pattern studies in which dogs, monkeys and rate received inhalation exposures to either 750/sup 0/C heat treated UO/sub 2/ + PuO/sub 2/, 1750/sup 0/C heat-treated (U,Pu)O/sub 2/ or 850/sup 0/C heat-treated pure PuO/sub 2/. The fourth paper described dose-response studies in which rats were exposed to (U,Pu)O/sub 2/ or pure PuO/sub 2/. This paper updates earlier reports and summarizes the status of animals through approximately 650 days after inhalation.

  18. α-1-Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression.

    Science.gov (United States)

    Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio

    2016-06-01

    Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes.

  19. Complex left profunda femoris vein to renal vein bypass for the management of progressive chronic iliofemoral occlusion.

    Science.gov (United States)

    Anaya-Ayala, Javier E; Adams, Matthew K; Telich-Tarriba, Jose E; Dresser, Kelly L; Ismail, Nyla; Peden, Eric K

    2013-01-01

    Chronic occlusions of the inferior vena cava (IVC) and iliofemoral veins are long-term sequelae of deep venous thrombosis (DVT) that can lead to postthrombotic syndrome (PTS). Patients may present with a wide spectrum of signs and symptoms, ranging from mild discomfort and swelling to severe venous hypertension and ulcerations. We report a 68-year-old man who had a history of left lower extremity DVT after a laminectomy and who developed PTS with nonhealing ulcers. The patient underwent a cross-pubic femorofemoral venous bypass that failed to improve his clinical status. After unsuccessful endovascular attempts for recanalization of the iliofemoral segment, a profunda femoris to IVC bypass was performed. The symptoms recurred 2 years later. Venography revealed restenosis at the caval anastomosis that did not resolve by endovascular means. A surgical revision was performed, and given the quality of the IVC, a jump bypass was created to the left renal vein. The swelling improved and the ulcers healed completely. Twenty-eight months after the complex reconstructions, he remains ulcer-free with mild edema controlled with stockings. Venous reconstructions remain a viable option for patients with symptomatic and recalcitrant nonmalignant obstruction of the large veins.

  20. Comment on “Recent progress in thermodynamics of radiation——exergy of radiation,effective temperature of photon and entropy constant of photon”

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Chen et al.proposed the concepts of effective temperature of photon and entropy constant of photon in a recent paper [Chen Z S,Mo S P,Hu P.Recent progress in thermodynamics of radiation―exergy of radiation,effective temperature of photon and entropy constant of photon.Sci China Ser E-Tech Sci,2008,51(8):1096―1109] by enduing a single photon with macroscale thermodynamic parameters such as exergy and entropy.This paper argues that applying these concepts and their inferences to macro-scale thermodynamic system will lead to the results which conflict with macroscale thermodynamic laws.This means that the concepts of effective temperature of photon and entropy constant of photon are not correct.

  1. [Influence of HFF-range radiation therapy upon dynamics of biochemical indices in patients with chronic generalized parodontitis].

    Science.gov (United States)

    Kazarina, L N; Okulova, Iu V

    2007-01-01

    Investigations were conducted on patients with a parodontitis in whome a low-intensive broad band electromagnetic radiation of the HFF-range was used in complex treatment. The authors confirmed that the EMR of the physiological intensity HFF leads to improvement of a parodontologic status and can be recommended in complex treatment of a parodontitis.

  2. Effects of orbit progression on the radiation exposures from solar proton fluxes in low Earth orbit under geomagnetic storm conditions.

    Science.gov (United States)

    Nealy, J E; Wilson, J W; Shea, M A; Smart, D F

    1996-01-01

    The present study examines the effects of orbit progression on the exposures within a Space Station Freedom module in a 51.6-degree inclined orbit at 450 km. The storm evolution is modeled after the November 1960 event, and the solar proton flux evolution is taken from the August 1972 solar proton event. The effects of a strong magnetic shock, such as was observed during the October 1989 event, is also modeled. The statistics on hourly average storm fields for the last forty years reveal that the largest geomagnetic storms approach a Dst value of -500 nanotesla at the storm peak. Similarly, one of the largest satellite-measured proton flux (> 10 MeV) for space exposures is the event of August 1972. The effects of orbit progression (advance of the line of nodes) is examined for the above conditions to study the variation of exposures under differing times of occurrence of the solar proton peak intensity, attainment of geomagnetic storm maximum, and the location of the line of nodes of the last geomagnetically protected orbit. The impact of the inherent inhomogeneity of the space station module is examined as a limiting factor on exposure with regard to the need of additional parasitic shielding.

  3. Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis

    Science.gov (United States)

    Cao, Qizhi; Didelot, Xavier; Wu, Zhongbiao; Li, Zongwei; He, Lihua; Li, Yunsheng; Ni, Ming; You, Yuanhai; Lin, Xi; Li, Zhen; Gong, Yanan; Zheng, Minqiao; Zhang, Minli; Liu, Jie; Wang, Weijun; Bo, Xiaochen; Falush, Daniel; Wang, Shengqi; Zhang, Jianzhong

    2015-01-01

    Objective To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. Design We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. Results The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. Conclusions Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy. PMID:25007814

  4. Further Insight Relative to Cavity Radiation: A Thought Experiment Refuting Kirchhoff's Law (Letters to Progress in Physics

    Directory of Open Access Journals (Sweden)

    Robitaille P.-M.

    2014-01-01

    Full Text Available Kirchhoff’s law of thermal emission demands that all cavities contain blackbody, or normal, radiation which is dependent solely on the temperature and the frequency of observation, while remaining independent of the nature of t he enclosure. For over 150 years, this law has stood as a great pillar for those who believe that gaseous stars could emit a blackbody spectrum. However, it is well-known that, u nder laboratory condi- tions, gases emit in bands and cannot produce a thermal spectrum. Furthermore, all laboratory blackbodies are constructed from nearly ideal a bsorbers. This fact strongly opposes the validity of Kirchhoff’s formulation. Clearly, if Kirchhoff had been correct, then laboratory blackbodies could be constructed of any arbitrary material. Through the use of two cavities in temperature equilibrium with one another, a thought experiment is presented herein which soundly refutes Kirchhoff’s law of thermal emission.

  5. Systemic Injection of RPE65-Programmed Bone Marrow-Derived Cells Prevents Progression of Chronic Retinal Degeneration.

    Science.gov (United States)

    Qi, Xiaoping; Pay, S Louise; Yan, Yuanqing; Thomas, James; Lewin, Alfred S; Chang, Lung-Ji; Grant, Maria B; Boulton, Michael E

    2017-04-05

    Bone marrow stem and progenitor cells can differentiate into a range of non-hematopoietic cell types, including retinal pigment epithelium (RPE)-like cells. In this study, we programmed bone marrow-derived cells (BMDCs) ex vivo by inserting a stable RPE65 transgene using a lentiviral vector. We tested the efficacy of systemically administered RPE65-programmed BMDCs to prevent visual loss in the superoxide dismutase 2 knockdown (Sod2 KD) mouse model of age-related macular degeneration. Here, we present evidence that these RPE65-programmed BMDCs are recruited to the subretinal space, where they repopulate the RPE layer, preserve the photoreceptor layer, retain the thickness of the neural retina, reduce lipofuscin granule formation, and suppress microgliosis. Importantly, electroretinography and optokinetic response tests confirmed that visual function was significantly improved. Mice treated with non-modified BMDCs or BMDCs pre-programmed with LacZ did not exhibit significant improvement in visual deficit. RPE65-BMDC administration was most effective in early disease, when visual function and retinal morphology returned to near normal, and less effective in late-stage disease. This experimental paradigm offers a minimally invasive cellular therapy that can be given systemically overcoming the need for invasive ocular surgery and offering the potential to arrest progression in early AMD and other RPE-based diseases.

  6. Chronic kidney disease progression to end stage renal disease: a single center experience of the role of the underlying kidney disease.

    Science.gov (United States)

    Ekart, Robert; Ferjuc, Anita; Furman, Barbara; Gerjevič, Špela; Bevc, Sebastjan; Hojs, Radovan

    2013-08-01

    Chronic kidney disease (CKD) is common and several factors affect its progression to end-stage renal disease (ESRD). The main goal of our study was to assess the influence of underlying kidney disease and some other important factors during the time of CKD progression to ESRD. A retrospective study of 91 patients (57 men, 34 women; average age 57.7 ± 13.2 years) was carried out. Patients were monitored at least one month before the first renal replacement treatment (RRT). Estimated glomerular filtration rate (eGFR) at first referral to nephrologist was determined by Modification of Diet in Renal Disease equation. Proteinuria was assessed semiquantitatively with dipsticks. Thirty-five patients (38.5%) had diabetic nephropathy (DN), 21 (23.1%) hypertensive nephrosclerosis (HN), 21 (23.1%) adult polycystic kidney disease (APKD) and 14 (15.4%) immunoglobulin A nephropathy (IgAN). Average eGFR at first referral for DN patients was 20.1, and then 23.4 for HN, 35.5 for APKD, and 36.4 mL/min per 1,73 m(2) for IgAN patients. Average time between first nephrological visit and first RRT was 28.4 months for DN patients, 41 for HN, 80.8 for APKD, and 70.1 for IgAN patients. Comparison of all four groups of CKD patients showed that in patients with APKD and IgAN impairment of kidney function to ESRD had progressed statistically significantly slower (P < 0.001). When eGFR at referral, proteinuria, smoking, and renin-angiontensin-aldosterone blockade treatment had been added into the model, patients with APKD and IgAN had a statistically significant longer period between first nephrological visit and first RRT (P < 0.026). In comparison with patients with other underlying causes of CKD, patients with APKD and IgAN had a statistically significant slower progression rate of CKD to ESRD.

  7. Fukushima simulation experiment: assessing the effects of chronic low-dose-rate internal 137Cs radiation exposure on litter size, sex ratio, and biokinetics in mice

    Science.gov (United States)

    Nakajima, Hiroo; Yamaguchi, Yoshiaki; Yoshimura, Takashi; Fukumoto, Manabu; Todo, Takeshi

    2015-01-01

    To investigate the transgenerational effects of chronic low-dose-rate internal radiation exposure after the Fukushima Daiichi Nuclear Power Plant accident in Japan, 18 generations of mice were maintained in a radioisotope facility, with free access to drinking water containing 137CsCl (0 and 100 Bq/ml). The 137Cs distribution in the organs of the mice was measured after long-term ad libitum intake of the 137CsCl water. The litter size and the sex ratio of the group ingesting the 137Cs water were compared with those of the control group, for all 18 generations of mice. No significant difference was noted in the litter size or the sex ratio between the mice in the control group and those in the group ingesting the 137Cs water. The fixed internal exposure doses were ∼160 Bq/g and 80 Bq/g in the muscles and other organs, respectively. PMID:26825299

  8. Mannan-binding lectin and healing of a radiation-induced chronic ulcer--a case report on mannan-binding lectin replacement therapy

    DEFF Research Database (Denmark)

    Maaløe, Nanna; Bonde, C; Laursen, I

    2011-01-01

    Mannan-binding lectin is an important component of innate immunity, and insufficiency is associated with several clinical disorders. Recently, experimental replacement therapy with plasma-derived mannan-binding lectin has become an option. The current article presents the case of a patient with a...... that deficiency of mannan-binding lectin can explain cases of otherwise unexplained impaired healing, and that replacement therapy is considered in such cases.......Mannan-binding lectin is an important component of innate immunity, and insufficiency is associated with several clinical disorders. Recently, experimental replacement therapy with plasma-derived mannan-binding lectin has become an option. The current article presents the case of a patient...... with an insufficient level of mannan-binding lectin and a chronic radiation-induced ulcer following the treatment of breast cancer. After 15 months of initially conservative treatment and thereafter plastic surgery, the healing was still impaired with necrosis in the periphery of the ulcer. Immunological work...

  9. Selective cyclooxygenase-2 inhibitor use and progression of renal function in patients with chronic kidney disease: a single-center retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Kaewput W

    2016-11-01

    Full Text Available Wisit Kaewput,1,2 Preedee Disorn,2 Bancha Satirapoj2 1Department of Military and Community Medicine, Phramongkutklao College of Medicine, 2Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Background: The use of selective COX-2 (sCOX-2 inhibitors with acute kidney injury, salt water retention, and cardiovascular events have been correlated in subjects with normal kidney function, but sCOX-2 inhibitor use concerning the progression of chronic kidney disease (CKD remains uncertain. Objectives: To determine the progression of renal function and electrolyte abnormalities among CKD patients after using sCOX-2 inhibitors during short- and long-term periods. Methods: The study employed a retrospective cohort design comprising all types of CKD patients with and without sCOX-2 inhibitors (celecoxib and etoricoxib. Data collected included medical data, estimated glomerular filtration rate (eGFR, and serum electrolytes at 3 and 6 months between January 2009 and January 2014. Subjects attended the outpatient clinic and were then followed up until discontinuation of the drugs at years 1 and 2 until May 2016. Results: Ninety-two CKD patients on sCOX-2 inhibitors and 92 CKD patients without sCOX-2 inhibitors were included. The sCOX-2 inhibitor group showed more decline in eGFR than the control group at 3 and 6 months of follow-up (–8.27±9.75 vs –1.64±6.05 mL/min/1.73 m2, P<0.001 and –12.36±6.48 vs –4.31±5.11 mL/min/1.73 m2, P=0.001, respectively and at 1 and 2 years of follow-up after subjects discontinued sCOX-2 (–6.84±10.34 vs –1.61±8.93 mL/min/1.73 m2, P=0.004 and –10.26±10.19 vs –5.12±8.61 mL/min/1.73 m2, P=0.005, respectively. In addition, the sCOX-2 inhibitor group had significantly more increased serum potassium during the study follow-up than the control group. Conclusion: The sCOX-2 inhibitors are associated with an increased risk for rapid eGFR decline and hyperkalemia in both the

  10. Effects of chronic methylphenidate on cocaine self-administration under a progressive-ratio schedule of reinforcement in rhesus monkeys.

    Science.gov (United States)

    Czoty, Paul W; Martelle, Susan E; Gould, Robert W; Nader, Michael A

    2013-06-01

    It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters. Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies. The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy. Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressive-ratio schedule of reinforcement in the evening. After cocaine (0.003-0.56 mg/kg per injection, i.v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0.003-0.0056 mg/kg per hour, i.v.; or 1.0-9.0 mg/kg p.o., b.i.d.) was administered for several weeks. A cocaine self-administration session was conducted every 7 days. When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined. In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine self-administration; it took several weeks for these effects to dissipate. These data are consistent with the largely negative results of clinical trials with MPD. In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence.

  11. Preoperative Proteinuria Is Associated with Long-Term Progression to Chronic Dialysis and Mortality after Coronary Artery Bypass Grafting Surgery

    Science.gov (United States)

    Wu, Pei-Chen; Wang, Wei-Jie; Chao, Chia-Ter; Yang, Shao-Yu; Shiao, Chih-Chung; Hu, Fu-Chang; Lai, Chun-Fu; Lin, Yu-Feng; Han, Yin-Yi; Chen, Yih-Sharng; Hsu, Ron-Bin; Young, Guang-Huar; Wang, Shoei-Shen; Tsai, Pi-Ru; Chen, Yung-Ming; Chao, Ting-Ting; Ko, Wen-Je; Wu, Kwan-Dun

    2012-01-01

    Aims Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long- term mortality and end -stage renal disease (ESRD) is unknown. Methods and Results We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all–cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long–term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). Conclusion Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients. PMID:22276092

  12. Preoperative proteinuria is associated with long-term progression to chronic dialysis and mortality after coronary artery bypass grafting surgery.

    Directory of Open Access Journals (Sweden)

    Vin-Cent Wu

    Full Text Available AIMS: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI, but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD is unknown. METHODS AND RESULTS: We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+ or heavy (2+ to 4+ according to the results of the dipstick test. A total of 276 (29.8% patients had mild proteinuria before surgery and 119 (12.9% patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17 was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88 and heavy proteinuria ([HR], 2.28 to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57 and heavy proteinuria ([HR], 2.70 exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD, which were independent of the baseline GFR and postoperative acute kidney injury (AKI. CONCLUSION: Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients.

  13. Development and Validation of a Scoring System for Predicting Periprocedural Complications During Percutaneous Coronary Interventions of Chronic Total Occlusions: The Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO) Complications Score.

    Science.gov (United States)

    Danek, Barbara Anna; Karatasakis, Aris; Karmpaliotis, Dimitri; Alaswad, Khaldoon; Yeh, Robert W; Jaffer, Farouc A; Patel, Mitul P; Mahmud, Ehtisham; Lombardi, William L; Wyman, Michael R; Grantham, J Aaron; Doing, Anthony; Kandzari, David E; Lembo, Nicholas J; Garcia, Santiago; Toma, Catalin; Moses, Jeffrey W; Kirtane, Ajay J; Parikh, Manish A; Ali, Ziad A; Karacsonyi, Judit; Rangan, Bavana V; Thompson, Craig A; Banerjee, Subhash; Brilakis, Emmanouil S

    2016-10-11

    High success rates are achievable for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using the hybrid approach, but periprocedural complications remain of concern. Although scores estimating success and efficiency in CTO PCI have been developed, there is currently no available score for estimation of the risk for periprocedural complications. We sought to develop a scoring tool for prediction of periprocedural complications during CTO PCI. We analyzed data from 1569 CTO PCIs in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO) using a derivation and validation sampling ratio of 2:1. Variables independently associated with periprocedural complications in multivariable analysis in the derivation set were assigned points based on their respective odds ratios. Forty-four (2.8%) patients experienced complications. Three factors were independent predictors of complications and were included in the score: patient age >65 years, +3 points (odds ratio, OR=4.85, CI 1.82-16.77); lesion length ≥23 mm, +2 points (OR=3.22, CI 1.08-13.89); and use of the retrograde approach +1 point (OR=2.41, CI 1.04-6.05). The resulting score showed good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow χ(2) 6.271, P=0.281, receiver-operating characteristic [ROC] area=0.758) and validation (Hosmer-Lemeshow χ(2) 4.551, P=0.473, ROC area=0.793) sets. Score values of 0 to 2, 3 to 4, and ≥5 were defined as low, intermediate, and high risk of complications (derivation cohort 0.4%, 1.8%, 6.5%, PCTO complication score is a useful tool for prediction of periprocedural complications in CTO PCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02061436. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. [Metabolic effect of amaranth oil and impulse hypoxic training under chronic fluoride intoxication and small doses of ionizing radiation].

    Science.gov (United States)

    Konyk, U V; Hzhehots'kyĭ, M P; Koval'chuk, S M

    2002-01-01

    Lipid peroxidation and antioxidative defence system in blood, liver and heart tissues, nitric oxide metabolites content in brain tissue of rats under binary action of small-doses of ionizing radiation and fluoride intoxication treated by amaranth oil and interval hypoxic training have been studied. Complex using of amaranth oil and interval hypoxic training result in increase both enzymatic, as nonezymatic links of antioxidant defence in all investigated tissues. It was revealed also enhance of NO system metabolites content in brain gomogenate. In this conditions lipid peroxidation processes in liver and heart tissues normalize comparison with essential increase level LPO under binary action influence. On the basis of obtained results LPO metabolites content we can suppossed that complex using of amaranth oil and interval hypoxic training result in increase of organism adaptative possibility. This complex can be using for binary action of ionizing radiation and fluoride intoxication correction.

  15. Interferon-γ production by tubulointerstitial human CD56(bright) natural killer cells contributes to renal fibrosis and chronic kidney disease progression.