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Sample records for alters pulmonary structure

  1. On the pathologically altered pulmonary pattern

    International Nuclear Information System (INIS)

    Ginzburg, M.A.; Kinoshenko, Yu.T.

    1982-01-01

    The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

  2. [Pulmonary alterations in Hodgkin lymphoma].

    Science.gov (United States)

    Jóna, Ádám; Illés, Árpád; Szemes, Katalin; Miltényi, Zsófia

    2016-01-31

    Most of Hodgkin lymphoma patients survive due to combined chemo/radiotherapy. Improved survival brings long-term side effects to the front, which may determine the patients' subsequent quality of life and expected lifetime. This manuscript aims to analyze lung manifestations of Hodgkin lymphoma and treatment related pulmonary complications, demonstrated with own cases. The lung involvement in Hodgkin lymphoma is often secondary, and primary pulmonary involvement is very rare. The authors found 8-12% of lung involvement among their patients. Side effects of treatment consist of pulmonary infections in conjuction with immunosuppression, while on the other hand bleomycin and chest irradiation as part of current standard of care induced pneumonitis and fibrosis are reported. The pulmonary involvement in Hodgkin lymphoma may cause differential diagnostic difficulty. Lung involvement could modify stage and consequently treatment, and the development of side effects might determine later quality of life and expected lifetime. Therefore, identification of lung involvement is crucial.

  3. Structural basis for pulmonary functional imaging

    International Nuclear Information System (INIS)

    Itoh, Harumi; Nakatsu, Masashi; Yoxtheimer, Lorene M.; Uematsu, Hidemasa; Ohno, Yoshiharu; Hatabu, Hiroto

    2001-01-01

    An understanding of fine normal lung morphology is important for effective pulmonary functional imaging. The lung specimens must be inflated. These include (a) unfixed, inflated lung specimen, (b) formaldehyde fixed lung specimen, (c) fixed, inflated dry lung specimen, and (d) histology specimen. Photography, magnified view, radiograph, computed tomography, and histology of these specimens are demonstrated. From a standpoint of diagnostic imaging, the main normal lung structures consist of airways (bronchi and bronchioles), alveoli, pulmonary vessels, secondary pulmonary lobules, and subpleural pulmonary lymphatic channels. This review summarizes fine radiologic normal lung morphology as an aid to effective pulmonary functional imaging

  4. Pulmonary biochemical alterations resulting from ozone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mustafa, M.G.; Lee, S.D.

    1976-07-01

    Metabolic response of lung tissue to ozone was studied in rats and monkeys after exposure of animals to various levels of ozone (0.1 to 0.8 ppM) for 1 to 30 days. In rats, 0.8 ppM ozone exposure resulted in a 40 to 50 percent augmentation of oxygen utilization in lung homogenate in the presence of an added substrate (e.g., succinate or 2-oxoglutarate). Activities of marker enzymes, viz. mitochondrial succinate-cytochrome c reductase; microsomal NADPH-cytochrome c reductase and cytosolic glucose-6-phosphate dehydrogenase, increased maximally (40 to 70 percent over control) after 3 to 4 days of exposure, and remained elevated throughout the 0.8 ppM ozone exposure for 30 days. In monkeys, the observations were the same except that the magnitude of biochemical changes was relatively smaller. Exposure of animals to lower levels of ozone resulted in proportionately smaller biochemical changes in the lung, and ozone effects were detectable up to the 0.2 ppM level. While 0.1 ppM ozone exposure was ineffective, dietary deficiency of vitamin E, a natural antioxidant, increased the sensitivity of rat lungs to this concentration of ozone. The results suggest that low-level ozone exposures may cause metabolic alterations in the lung, and that dietary supplementation of vitamin E may offer protection against oxidant stress.

  5. Radiodiagnosis of pulmonary alterations in systemic lupus erythematosus patients

    Energy Technology Data Exchange (ETDEWEB)

    Kamenetskij, M.S.; Lezova, T.F.; Kajzerman, I.A.; Sinyachenko, O.V.; Dyadyk, A.I.; Nikolenko, Yu.I. (Donetskij Meditsinskij Inst. (Ukrainian SSR))

    X-ray examination was carried out in 170 patients with systemic lupus erythematosus. Certain parameters of specific immunity were studied in 60 of them, while X-ray data were compared with morphological findings on autopsy in 20 cases. A tendency toward escalation of specific cell and humoral parameters was discovered in pulmonary lesion, predetermined by vasculitis and perivasculitis, as well as inflammatory and fibrotic alterations in the interstitial tissue.

  6. Radiodiagnosis of pulmonary alterations in systemic lupus erythematosus patients

    International Nuclear Information System (INIS)

    Kamenetskij, M.S.; Lezova, T.F.; Kajzerman, I.A.; Sinyachenko, O.V.; Dyadyk, A.I.; Nikolenko, Yu.I.

    1982-01-01

    X-ray examination was carried out in 170 patients with systemic lupus erythematosus. Certain parameters of specific immunity were studied in 60 of them, while X-ray data were compared with morphological findings on autopsy in 20 cases. A tendency toward escalation of specific cell and humoral parameters was discovered in pulmonary lesion, predetermined by vasculitis and perivasculitis, as well as inflammatory and fibrotic alterations in the interstitial tissue

  7. Pleural and pulmonary alterations caused by rheumatoid arthritis

    International Nuclear Information System (INIS)

    Bankier, A.A.; Fleischmann, D.; Kiener, H.P.; Wiesmayr, M.N.; Herold, C.J.

    1996-01-01

    Pulmonary complications caused by rheumatoid arthritis are a clinically relevant aspect of this chronic arthropathy. This article reviews pulmonary abnormalities induced by rheumatoid arthritis and their clinical and radiological findings. In addition, the role of different imaging modalities in the diagnostic work-up of pulmonary complications caused by rheumatoid arthritis is discussed. (orig./MG) [de

  8. Radiodiagnosis of pulmonary alterations induced by organophosphorus insecticides poisoning

    International Nuclear Information System (INIS)

    Kishkovskij, A.N.; Tyutin, L.A.; Ivanov, N.V.

    1982-01-01

    In order to assess possibilities of radiodiagnosis of pulmonary complications, developing as a result of organophosphorus insecticides poisoning, clinical and X-ray examination of 400 patients, aged 17 to 73 years, has been carried out. The lung plethora was manifested by a symmetric emlargement of the lung roots and vessels. A diffuse cleaness of the lung pattern, lung root widening and structural disorder, as well as an appearance of the small focal shadows in the hilar zones, were all characteristic of interstitial edema. X-ray signs of alveolar edema were confined to the coalescing shadows of different size and intensity, and to a massive infiltration of both the lung roots and emphysematous zones. The pneumonic infiltration foci of the lung parenchyma were usually distributed in the peripheral segments. Routine radiography in lateral projection played a decisive role in atelectasis diagnosis

  9. Late Posthemorrhagic Structural and Functional Changes in Pulmonary Circulation Arteries

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    S. A. Andreyeva

    2008-01-01

    Full Text Available Objective: to reveal the major regularities and mechanisms of morphological changes in the rat pulmonary circulation arteries in the late posthemorrhagic period and to compare them with age-related features of the vessels. Materials and methods: experiments to generate graduated hemorrhagic hypotension with the blood pressure being maintained at 40 mm Hg were carried out on young (5—6-month albino male Wistar rats. Throughout hypotension and 60 days after blood loss, the blood was tested to determine low and average molecular-weight substances by spectrophotometry and the pro- and antioxidative systems by chemiluminescence. Pulmonary circulation arteries were morphologically studied in young animals, rats in the late posthemorrhagic period and old (24—25-month rats. Results. Sixty-minute hemorrhagic hypotension leads to the development of endotoxemia and imbalance of the pro- and antioxidative systems, the signs of which are observed in the late periods (2 months after hypotension. At the same time, the posthemorrhagic period is marked by the significant pulmonary circulation arterial morphological changes comparable with their age-related alterations in old rat. This shows up mainly in the reorganization of a connective tissue component in the vascular wall: the elevated levels of individual collagen fibers, their structural changes, elastic medial membrane destruction and deformity. At the same time, there is a change in the morphometric parameters of vessels at all study stages while their lowered flow capacity is only characteristic for intraorgan arteries. Conclusion: The increased activity of free radical oxidation and endotoxemia may be believed to be one of the causes of morphological changes in pulmonary circulation arteries in the late posthemorrhagic period, which is similar to age-related vascular alterations. Key words: hemorrhagic hypotension, pulmonary circulation arteries, free radical oxidation, endotoxemia, remodeling, late

  10. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    Science.gov (United States)

    ... Methamphetamine Alters Brain Structures, Impairs Mental Flexibility Email Facebook Twitter March 20, 2014 A new study adds to the copious existing evidence that chronic exposure to addictive drugs alters the brain in ways that make ...

  11. Alteration of pulmonary blood flow in tetralogy of Fallot

    International Nuclear Information System (INIS)

    Hashimoto, Kazuhiro; Matsui, Michihiko; Kurosawa, Hiromi; Arai, Tatsuta; Nakamura, Yuzuru.

    1992-01-01

    The pulmonary blood distribution was examined in 17 patients with tetralogy of Fallot (TOF) pre and postoperatively with macroaggregates of 99m TC-labeled human serum albumin. Most of the patients with TOF demonstrated an abnormal preoperative distribution pattern. The abnormalities included not only an unbalanced distribution between the right and left lungs but also a maldistribution of peripheral vessels in each lung. The right/left lung counts ratio and pulmonary peripheral index (calculated in order to express the severity of peripheral maldistribution) correlated neither to the diameter nor the cross-sectional area of either right or left pulmonary arteries which were measured angiographically. Postoperatively, the pulmonary blood was shunted toward the developed side of the lung which further contributed to maldistribution of blood flow and unbalanced pulmonary growth. Since the patients with an unbalanced pulmonary blood distribution demonstrated a higher right ventricular pressure one year after the operation, a palliative operation facilitating the growth of the underdeveloped side of the lung might be considered as an effective procedure to precede intracardiac repair. (author)

  12. The effect of altering pulmonary blood flow on pulmonary gas exchange in the turtle Trachemys (Pseudemys) scripta.

    Science.gov (United States)

    Hopkins, S R; Wang, T; Hicks, J W

    1996-10-01

    In resting reptiles, the PO2 of pulmonary venous return (PLAO2; left atrial blood) may be 20 mmHg (1 mmHg = 0.1333 kPa) lower than the PO2 of gas in the lung. This level of PO2 is considerably higher than that observed in resting mammals and birds and results from ventilation-perfusion (V/Q) heterogeneity, pulmonary diffusion limitation and intrapulmonary shunting. However, the relative contribution of each of these factors is unknown. Many reptiles, particularly chelonians, exhibit an intermittent ventilation pattern where pulmonary blood flow (QL) increases during the ventilatory periods and, therefore, we hypothesized that V/Q matching would improve with increasing QL. We applied the multiple inert gas elimination technique in anaesthetized turtles at 22 degrees C. Turtles were continuously ventilated at a rate of 140 ml kg-1 min-1, equivalent to the rate of ventilation within a ventilatory period. Trace amounts of six inert gases were infused through the jugular vein. Blood samples from the pulmonary artery and the left atrium and mixed expired gases were collected for analysis. QL was reduced by a factor of six (low flow) using a vascular occluder placed around the common pulmonary artery or increased by a factor of two (high flow) through bolus injection of adrenaline. V/Q heterogeneity was significantly reduced with increasing pulmonary blood flow (P means +/- S.E.M.) and PLAO2 increased significantly (P < 0.05) from 88 +/- 17 mmHg (low flow) to 120 +/- 14 mmHg (high flow). There was evidence of pulmonary diffusion limitation under all conditions, which was unchanged with increasing blood flow. These findings suggest that increased pulmonary blood flow during a ventilatory period results in both temporal and spatial matching of ventilation and perfusion, without altering pulmonary diffusion limitation.

  13. STRUCTURAL ALTERATIONS OF SKELETAL MUSCLE IN COPD

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    Sunita eMathur

    2014-03-01

    Full Text Available Background: Chronic obstructive pulmonary disease (COPD is a respiratory disease associated with a systemic inflammatory response. Peripheral muscle dysfunction has been well characterized in individuals with COPD and results from a complex interaction between systemic and local factors. Objective: In this narrative review, we will describe muscle wasting in people with COPD, the associated structural changes, muscle regenerative capacity and possible mechanisms for muscle wasting. We will also discuss how structural changes relate to impaired muscle function and mobility in people with COPD. Key Observations: Approximately 30-40% of individuals with COPD experience muscle mass depletion. Furthermore, muscle atrophy is a predictor of physical function and mortality in this population. Associated structural changes include a decreased proportion and size of type-I fibers, reduced oxidative capacity and mitochondrial density mainly in the quadriceps. Observations related to impaired muscle regenerative capacity in individuals with COPD include a lower proportion of central nuclei in the presence or absence of muscle atrophy and decreased maximal telomere length, which has been correlated with reduced muscle cross-sectional area. Potential mechanisms for muscle wasting in COPD may include excessive production of reactive oxygen species, altered amino acid metabolism and lower expression of peroxisome proliferator-activated receptors-gamma-coactivator 1-alpha mRNA. Despite a moderate relationship between muscle atrophy and function, impairments in oxidative metabolism only seems weakly related to muscle function. Conclusion: This review article demonstrates the cellular modifications in the peripheral muscle of people with COPD and describes the evidence of its relationship to muscle function. Future research will focus on rehabilitation strategies to improve muscle wasting and maximize function.

  14. Vitamin A deficiency alters the pulmonary parenchymal elastic modulus and elastic fiber concentration in rats

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    Holmes Amey J

    2005-07-01

    Full Text Available Abstract Background Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA or remained unsupplemented. Methods Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion. Results VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98°, decreased in VAD and was not restored after 21 days of RA-treatment. Conclusion Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.

  15. Does ECT alter brain structure?

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    Devanand, D P; Dwork, A J; Hutchinson, E R; Bolwig, T G; Sackeim, H A

    1994-07-01

    The purpose of this study was to evaluate whether ECT causes structural brain damage. The literature review covered the following areas: cognitive side effects, structural brain imaging, autopsies of patients who had received ECT, post-mortem studies of epileptic subjects, animal studies of electroconvulsive shock (ECS) and epilepsy, and the neuropathological effects of the passage of electricity, heat generation, and blood-brain barrier disruption. ECT-induced cognitive deficits are transient, although spotty memory loss may persist for events immediately surrounding the ECT course. Prospective computerized tomography and magnetic resonance imaging studies show no evidence of ECT-induced structural changes. Some early human autopsy case reports from the unmodified ECT era reported cerebrovascular lesions that were due to agonal changes or undiagnosed disease. In animal ECS studies that used a stimulus intensity and frequency comparable to human ECT, no neuronal loss was seen when appropriate control animals, blind ratings, and perfusion fixation techniques were employed. Controlled studies using quantitative cell counts have failed to show neuronal loss even after prolonged courses of ECS. Several well-controlled studies have demonstrated that neuronal loss occurs only after 1.5 to 2 hours of continuous seizure activity in primates, and adequate muscle paralysis and oxygenation further delay these changes. These conditions are not approached during ECT. Other findings indicate that the passage of electricity, thermal effects, and the transient disruption of the blood-brain barrier during ECS do not result in structural brain damage. There is no credible evidence that ECT causes structural brain damage.

  16. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

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    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  17. Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension.

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    Richard B Rothman

    Full Text Available The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/- mice were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(-/- mice. We postulated that: 1 Tph1(-/- mice express lower levels of pulmonary 5-HT transporter (SERT when compared to wild-type controls, and 2 Tph1(-/- mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR. Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(-/- mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(-/- mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(-/- mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized.

  18. Pathophysiological roles of microvascular alterations in pulmonary inflammatory diseases: possible implications of tumor necrosis factor-alpha and CXC chemokines

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    Kanami Orihara

    2008-10-01

    Full Text Available Kanami Orihara, Akio MatsudaDepartment of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, JapanAbstract: Chronic obstructive pulmonary disease (COPD and bronchial asthma are common respiratory diseases that are caused by chronic infl ammation of the airways. Although these diseases are mediated by substantially distinct immunological reactions, especially in mild cases, they both show increased numbers of neutrophils, increased production of tumor necrosis factor-alpha (TNF-α and poor responses to corticosteroids, particularly in patients with severe diseases. These immunological alterations may contribute strongly to airway structural changes, commonly referred to as airway remodeling. Microvascular alterations, a component of airway remodeling and caused by chronic inflammation, are observed and appear to be clinically involved in both diseases. It has been well established that vascular endothelial growth factor (VEGF plays important roles in the airway microvascular alterations in mild and moderate cases of both diseases, but any role that VEGF might play in severe cases of these diseases remains unclear. Here, we review recent research findings, including our own data, and discuss the possibility that TNF-α and its associated CXC chemokines play roles in microvascular alterations that are even more crucial than those of VEGF in patients with severe COPD or asthma.Keywords: TNF-α, CXC chemokines, corticosteroid, pulmonary microvessels, COPD, asthma

  19. Categorization of nano-structured titanium dioxide according to physicochemical characteristics and pulmonary toxicity

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    Naoki Hashizume

    Full Text Available A potentially useful means of predicting the pulmonary risk posed by new forms of nano-structured titanium dioxide (nano-TiO2 is to use the associations between the physicochemical properties and pulmonary toxicity of characterized forms of TiO2. In the present study, we conducted intratracheal administration studies in rats to clarify the associations between the physicochemical characteristics of seven characterized forms of TiO2 and their acute or subacute pulmonary inflammatory toxicity. Examination of the associations between the physicochemical characteristics of the TiO2 and the pulmonary inflammatory responses they induced revealed (1 that differences in the crystallinity or shape of the TiO2 particles were not associated with the acute pulmonary inflammatory response; (2 that particle size was associated with the acute pulmonary inflammatory response; and (3 that TiO2 particles coated with Al(OH3 induced a greater pulmonary inflammatory response than did non-coated particles. We separated the seven TiO2 into two groups: a group containing the six TiO2 with no surface coating and a group containing the one TiO2 with a surface coating. Intratracheal administration to rats of TiO2 from the first group (i.e., non-coated TiO2 induced only acute pulmonary inflammatory responses, and within this group, the acute pulmonary inflammatory response was equivalent when the particle size was the same, regardless of crystallinity or shape. In contrast, intratracheal administration to rats of the TiO2 from the second group (i.e., the coated TiO2 induced a more severe, subacute pulmonary inflammatory response compared with that produced by the non-coated TiO2. Since alteration of the pulmonary inflammatory response by surface treatment may depend on the coating material used, the pulmonary toxicities of coated TiO2 need to be further evaluated. Overall, the present results demonstrate that physicochemical properties may be useful for predicting the

  20. Geophysical Identification of Hydrothermally Altered Structures That ...

    African Journals Online (AJOL)

    This research study uses geophysical method (aeromagnetic) to identify hydrothermally altered structures which favour the inflow of hydrothermal fluid that usually brings about gold mineralisation in Egbe-Isanlu Schist Belt Area, North Central Nigeria. The application of data enhancement filtering algorithm such as ...

  1. Alterations of N-3 Polyunsaturated Fatty Acid-Activated K2P Channels in Hypoxia-Induced Pulmonary Hypertension

    DEFF Research Database (Denmark)

    Nielsen, Gorm; Wandall-Frostholm, Christine; Sadda, Veeranjaneyulu

    2013-01-01

    in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch...... a novel counter-regulatory mechanism in pulmonary hypertension and suggest that arterial K2P 2.1 and K2P 6.1 could be novel therapeutic targets....

  2. Altered pulmonary defense system in lung injury induced by didecyldimethylammonium chloride in mice.

    Science.gov (United States)

    Ohnuma, Aya; Yoshida, Toshinori; Horiuchi, Haruka; Fukumori, Junko; Tomita, Mariko; Kojima, Sayuri; Takahashi, Naofumi; Fukuyama, Tomoki; Hayashi, Koichi; Yamaguchi, Satoru; Ohtsuka, Ryoichi; Kashimoto, Yukiko; Kuwahara, Maki; Takeda, Makio; Kosaka, Tadashi; Nakashima, Nobuaki; Harada, Takanori

    2011-07-01

    Didecyldimethylammonium chloride (DDAC), a representative dialkyl-quaternary ammonium compound (QAC), could contaminate working atmospheres when used in disinfectant operation and adversely affect human health. Furthermore, the development of bacteria resistant to DDAC might become public health concern. We postulated that DDAC instillation in the lungs alters pulmonary antioxidant and antimicrobial responses and increases susceptibility to systemic administration of a bacterial component lipopolysaccharide (LPS). Mice were intratracheally instilled with DDAC and sacrificed 1, 3, or 7 days after treatment. Pulmonary cytotoxicity in recovered bronchoalveolar lavage was evident on Days 1 and 7, and inflammatory cell influx and interleukin-6 expression peaked on Day 7, in association with altered antioxidant and antimicrobial responses, as demonstrated by measuring heme oxygenase-1, glutathione peroxidase 2, lactoferrin, and mouse β-defensin-2 and -3 mRNA in the lung samples. The impaired defense system tended to enhance the inflammatory reaction caused by a systemic administration of LPS; the effect was in association with increased expression of toll-like receptor-4 mRNA. The results suggest that DDAC alters pulmonary defense system, which may contribute to susceptibility to an exogenous infectious agent.

  3. Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension

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    Yun-Ping Mu

    2016-07-01

    Full Text Available Background/Aims: Alterations in intracellular Ca2+ concentration ([Ca2+]i underlie the pathogenesis of various cardiovascular diseases. Caveolin-1 (Cav-1 is the primary functional protein associated with caveolae, which are invaginations in the plasma membrane, and is a regulator of [Ca2+]i signaling. Caveolae and Cav-1 increase the activity of store-operated Ca2+ channels (SOCC in rat pulmonary arterial smooth muscle cells (PASMCs, and these enhancing effects were more pronounced in rats with pulmonary hypertension (PH. Classical transient receptor potential (TRPC proteins are highly expressed in vascular smooth muscle cells, and these proteins form functional receptor-operated Ca2+ channels (ROCC and SOCC in PASMCs. Previous studies suggested that functional and structural changes in aortas might occur during the pathological process of PH. Our data demonstrated that Cav-1 and TRPC were also abundant in the aorta smooth muscle cells (AoSMCs of PH rats. However, previous PH research primarily focused on Ca2+ channels in pulmonary arteries, but not functional changes in Ca2+ channels in aortas. The contribution of Cav-1 of AoSMCs to alterations of Ca2+ signaling in aortic functions during the pathological process of PH has not been fully characterized. Therefore, this study investigated alterations in Cav-1 expression and the relationship of these changes to Ca2+ channels in AoSMCs of PH rats. Methods: The present study examined physiological caveolae and Cav-1 expression and characterized the function of altered Cav-1 expression in rat aortas with PH. Results: The appearance of caveolae with Cav-1 expression increased significantly in the aortas of rats with PH, but TRPC1 and TRPC6 expression was not altered. In vitro experiments demonstrated that caveolae contributed to phenylephrine, endothelin-1, and 1-oleoyl-2-acetyl-sn-glycerol (OAG-induced aortic vasoreactivity, but KCl and cyclopiazonic acid had no effect, which suggests the vital

  4. Altered microRNA signatures in sputum of patients with active pulmonary tuberculosis.

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    Zhengjun Yi

    Full Text Available Role of microRNA (miRNA has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differentially expressed between tuberculosis group and controls. More miRNAs (52 out of 95 miRNAs were underexpressed than overexpressed during tuberculosis infection. Overexpression of miR-3179, miR-147 and underexpression of miR-19b-2* in TB group compared with controls were confirmed in the validation cohort. TNF-α and IL-6 levels were not significantly altered between TB group and controls. For the first time, differential expression of miRNAs in sputum was found in active pulmonary tuberculosis. The study provides rationale for identifying the role of miRNAs in the pathogenesis of pulmonary tuberculosis and indicates potential for miRNA-based therapeutic strategies.

  5. Altered microRNA signatures in sputum of patients with active pulmonary tuberculosis.

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    Yi, Zhengjun; Fu, Yurong; Ji, Rui; Li, Ruifang; Guan, Zhiyu

    2012-01-01

    Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differentially expressed between tuberculosis group and controls. More miRNAs (52 out of 95 miRNAs) were underexpressed than overexpressed during tuberculosis infection. Overexpression of miR-3179, miR-147 and underexpression of miR-19b-2* in TB group compared with controls were confirmed in the validation cohort. TNF-α and IL-6 levels were not significantly altered between TB group and controls. For the first time, differential expression of miRNAs in sputum was found in active pulmonary tuberculosis. The study provides rationale for identifying the role of miRNAs in the pathogenesis of pulmonary tuberculosis and indicates potential for miRNA-based therapeutic strategies.

  6. Disease-associated mutations that alter the RNA structural ensemble.

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    Matthew Halvorsen

    2010-08-01

    Full Text Available Genome-wide association studies (GWAS often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs from the Human Gene Mutation Database (HGMD that map to the untranslated regions (UTRs of a gene. Rather than using minimum free energy approaches (e.g. mFold, we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, beta-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD, and Hypertension, we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5' UTRs of FTL and RB1 SNP-induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a "RiboSNitch," that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble.

  7. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

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    Qi Yuhua

    2012-12-01

    Full Text Available Abstract Background Pulmonary tuberculosis (TB is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP, varicella-zoster virus (VZV and enterovirus (EV were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated. Following qRT-PCR confirmation and receiver operational curve (ROC analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC value range, 0.711-0.848. Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

  8. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection.

    Science.gov (United States)

    Qi, Yuhua; Cui, Lunbiao; Ge, Yiyue; Shi, Zhiyang; Zhao, Kangchen; Guo, Xiling; Yang, Dandan; Yu, Hao; Cui, Lan; Shan, Yunfeng; Zhou, Minghao; Wang, Hua; Lu, Zuhong

    2012-12-28

    Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

  9. Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

    Science.gov (United States)

    Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

    2016-04-01

    Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

  10. Altered structural connectome in temporal lobe epilepsy.

    Science.gov (United States)

    DeSalvo, Matthew N; Douw, Linda; Tanaka, Naoaki; Reinsberger, Claus; Stufflebeam, Steven M

    2014-03-01

    To study differences in the whole-brain structural connectomes of patients with left temporal lobe epilepsy (TLE) and healthy control subjects. This study was approved by the institutional review board, and all individuals gave signed informed consent. Sixty-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) magnetic resonance imaging volumes were analyzed in 24 patients with left TLE and in 24 healthy control subjects. MP-RAGE volumes were segmented into 1015 regions of interest (ROIs) spanning the entire brain. Deterministic white matter tractography was performed after voxelwise tensor calculation. Weighted structural connectivity matrices were generated by using the pairwise density of connecting fibers between ROIs. Graph theoretical measures of connectivity networks were compared between groups by using linear models with permutation testing. Patients with TLE had 22%-45% reduced (P < .01) distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with that in healthy subjects. However, local connectivity, as measured by means of network efficiency, was increased by 85%-270% (P < .01) in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE as compared with healthy subjects. This study suggests that TLE involves altered structural connectivity in a network that reaches beyond the temporal lobe, especially in the default mode network.

  11. Pulmonary artery endothelial cell phenotypic alterations in a large animal model of pulmonary arteriovenous malformations after the Glenn shunt.

    Science.gov (United States)

    Kavarana, Minoo N; Mukherjee, Rupak; Eckhouse, Shaina R; Rawls, William F; Logdon, Christina; Stroud, Robert E; Patel, Risha K; Nadeau, Elizabeth K; Spinale, Francis G; Graham, Eric M; Forbus, Geoffrey A; Bradley, Scott M; Ikonomidis, John S; Jones, Jeffrey A

    2013-10-01

    Longevity of the superior cavopulmonary connection (SCPC) is limited by the development of pulmonary arteriovenous malformations (PAVM). The goal of this study was to determine whether phenotypic changes in pulmonary artery endothelial cells (PAEC) that favor angiogenesis occur with PAVM formation. A superior vena cava to right pulmonary artery connection was constructed in 5 pigs. Pulmonary arteries were harvested at 6 to 8 weeks after surgery to establish cultures of PAEC and smooth muscle cells, to determine cell proliferation, gene expression, and tubule formation. Abundance of proteins related to angiogenesis was measured in lung tissue. Contrast echocardiography revealed right-to-left shunting, consistent with PAVM formation. While the proliferation of smooth muscle cells from the right pulmonary artery (shunted side) and left pulmonary artery (nonshunted side) were similar, right PAEC proliferation was significantly higher. Expression profiles of genes encoding cellular signaling proteins were higher in PAECs from the right pulmonary artery versus left pulmonary artery. Protein abundance of angiopoietin-1, and Tie-2 (angiopoietin receptor) were increased in the right lung (both p SCPC concomitantly with differential changes in PAEC proliferative ability and phenotype. Moreover, there was a significant increase in the angiopoietin/Tie-2 complex in the right lung, which may provide novel therapeutic targets to attenuate PAVM formation after a SCPC. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke.

    Science.gov (United States)

    Wolf, Lisa; Herr, Christian; Niederstraßer, Julia; Beisswenger, Christoph; Bals, Robert

    2017-01-01

    The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

  13. Receptor for advanced glycation endproducts (RAGE maintains pulmonary structure and regulates the response to cigarette smoke.

    Directory of Open Access Journals (Sweden)

    Lisa Wolf

    Full Text Available The receptor for advanced glycation endproducts (RAGE is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/- mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

  14. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    Directory of Open Access Journals (Sweden)

    Christopher B Massa

    2017-08-01

    Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

  15. Pulmonary Artery Endothelial Cell Phenotypic Alterations in a Large Animal Model of Pulmonary Arteriovenous Malformations Following the Glenn Shunt

    Science.gov (United States)

    Kavarana, Minoo N.; Mukherjee, Rupak; Eckhouse, Shaina R.; Rawls, William F.; Logdon, Christina; Stroud, Robert E.; Patel, Risha K.; Nadeau, Elizabeth K.; Spinale, Francis G.; Graham, Eric M.; Forbus, Geoffrey A.; Bradley, Scott M.; Ikonomidis, John S.; Jones, Jeffrey A.

    2014-01-01

    Background: Longevity of the superior cavopulmonary connection (SCPC) is limited by the development of pulmonary arteriovenous malformations (PAVM). The goal of this study was to determine whether phenotypic changes in pulmonary artery endothelial cells (PAEC) that favor angiogenesis occur with PAVM formation. Methods: A superior vena cava to right pulmonary artery connection was constructed in 5 pigs. Pulmonary arteries were harvested at 6-8 weeks following surgery to establish cultures of PAEC and smooth muscle cells, to determine cell proliferation, gene expression, and tubule formation. Abundance of proteins related to angiogenesis was measured in lung tissue. Results: Contrast echocardiography revealed right-to-left shunting, consistent with PAVM formation. While the proliferation of smooth muscle cells from the right pulmonary artery (RPA) (shunted side) and left pulmonary artery (LPA) (non- shunted side) were similar, right PAEC proliferation was significantly higher. Expression profiles of genes encoding cellular signaling proteins were higher in PAECs from the RPA vs. LPA. Protein abundance of angiopoietin-1, and Tie-2 (angiopoietin receptor) were increased in the right lung (both pSCPC. This study found that PAVM development occurred concomitantly with differential changes in PAEC proliferative ability and phenotype. Moreover, there was a significant increase in the angiopoietin/Tie-2 complex in the right lung, which may provide novel therapeutic targets to attenuate PAVM formation following a SCPC. PMID:23968766

  16. Alterations in cardiomyocyte function after pulmonary treatment with stainless steel welding fume in rats.

    Science.gov (United States)

    Popstojanov, Risto; Antonini, James M; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B; Kan, Hong

    2014-01-01

    Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.

  17. [Regulatory role of calcium activated chloride channel in pulmonary vascular structural remodeling in rats with pulmonary arterial hypertension induced by high pulmonary blood flow].

    Science.gov (United States)

    Wang, K; Pang, Y S; Su, D Y; Ye, B B; Qin, S Y; Liu, D L; Han, Y L

    2016-09-01

    To explore the regulatory role of calcium activated chloride channel (CaCC) in vascular structural remodeling in pathogenesis of pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow. An abdominal aorta and inferior vena cava shunting operation was used to induce high pulmonary blood flow and establish a PAH rat model.Seventy-five SD rats were randomly divided into normal, sham, shunt, niflumic acid (NFA) 1(0.2 mg/(kg·d))and NFA 2 (0.4 mg/(kg·d)) groups. There were 15 rats in each group. Pulmonary artery pressure and vascular structural remodeling were measured, arteriole contraction ratio among these groups were compared using vascular tone analysis system, and the electrophysiology of pulmonary artery smooth muscle cell (PASMC) was recorded using patch clamp technology. Differences between multiple groups were compared through variance analysis and that between groups with q test. Compared with normal ((14.4±1.3 ) mmHg, 1 mmHg=0.133 kPa)and sham groups ((13.5±2.3 ) mmHg), mean pulmonary artery pressure in shunt group ((27.4±2.4 ) mmHg) increased significantly (Ppulmonary artery pressure in NFA 1 group ((21.2±2.0) mmHg) and NFA 2 group ((22.3±2.0) mmHg) decreased significantly (PPulmonary vascular structural remodeling including pulmonary artery stenosis presented in shunt group. Compared with normal ((114.3±1.2)%) and sham ((115.5±1.1)%) groups, arteriole contraction ratio to 10(-5) mol/L phenylephrine in shunt group ((132.6±1.4)%) increased significantly (Ppulmonary vascular structural remodeling alleviated in NFA 1 and NFA 2 groups. Arteriole contraction ratio in NFA 1 group ((126.4±1.3)%) and NFA 2 group ((124.6±1.0)%) decreased significantly compared with shunt group (Ppulmonary arterial hypertension induced by high pulmonary blood flow through regulating membrane potential. NFA attenuate pulmonary vascular structural remodeling and pulmonary pressure through decreasing CaCC current density of PASMC membrane.

  18. Right ventricular Hemodynamic Alteration after Pulmonary Valve Replacement in Children with Congenital Heart Disease

    Directory of Open Access Journals (Sweden)

    Hamid Bigdelian

    2015-03-01

    Full Text Available Introduction:  In patients who underwent surgery to repair Tetralogy of Fallot, right ventricular dilation from pulmonary regurgitation may be result in right ventricular failure, arrhythmias and cardiac arrest. Hence, pulmonary valve replacement may be necessary to reduce right ventricular volume overload. The aim of present study was to assess the effects of pulmonary valve replacement on right ventricular function after repair of Tetralogy of Fallot.   Materials and  Method:  This retrospective study was carried out between July 2011 and October 2013 on 21 consecutive patients in Chamran Heart Center (Esfahan. The study included 13 male (61.9% and 8 female (38.1%. Cardiac magnetic resonance was performed before, 6 and 12 months after pulmonary valve replacement in all patients (Babak Imaging Center, Tehran with the 1.5 Tesla system. The main reason for surgery at Tetralogy of Fallot repaired time was Tetralogy of Fallot + Pulmonary insufficiency (17 cases and Tetralogy of Fallot + Pulmonary atresia (4 cases. Right ventricular function was assessed before and after pulmonary valve replacement with Two-dimensional echocardiography and ttest was used to evaluate follow-up data.   Results:  Right ventricular end-diastolic volume, right ventricular end- systolic volume significantly decreased (P value ˂ 0.05.Right ventricular ejection fraction had a significant increase (P value ˂ 0.05. Right ventricular mass substantially shrank after pulmonary valve replacement. Moreover, pulmonary regurgitation noticeably decreased in patients. The other hemodynamic parameter such as left ventricular ejection fraction improved but was not significant (P value= 0.79. Conclusion:  Pulmonary valve replacement can successfully restores the impaired hemodynamic function of right ventricle which is caused by direct consequence of volume unloading in patient. Pulmonary valve surgery in children with Tetralogy of Fallot who have moderate to severe pulmonary

  19. Right ventricular Hemodynamic Alteration after Pulmonary Valve Replacement in Children with Congenital Heart Disease

    OpenAIRE

    Hamid Bigdelian; Mohsen Sedighi; Davoud Mardani

    2015-01-01

    Introduction:  In patients who underwent surgery to repair Tetralogy of Fallot, right ventricular dilation from pulmonary regurgitation may be result in right ventricular failure, arrhythmias and cardiac arrest. Hence, pulmonary valve replacement may be necessary to reduce right ventricular volume overload. The aim of present study was to assess the effects of pulmonary valve replacement on right ventricular function after repair of Tetralogy of Fallot.   Materials and  Method:  This retrospe...

  20. Altered vasoreactivity in neonatal rats with pulmonary hypertension associated with bronchopulmonary dysplasia: Implication of both eNOS phosphorylation and calcium signaling.

    Directory of Open Access Journals (Sweden)

    Eric Dumas de la Roque

    Full Text Available Bronchopulmonary dysplasia (BPD consists of an arrest of pulmonary vascular and alveolar growth, with persistent hypoplasia of the pulmonary microvasculature and alveolar simplification. In 25 to 40% of the cases, BPD is complicated by pulmonary hypertension (BPD-PH that significantly increases the risk of morbidity. In vivo studies suggest that increased pulmonary vascular tone could contribute to late PH in BPD. Nevertheless, an alteration in vasoreactivity as well as the mechanisms involved remain to be confirmed. The purpose of this study was thus to assess changes in pulmonary vascular reactivity in a murine model of BPD-PH. Newborn Wistar rats were exposed to either room air (normoxia or 90% O2 (hyperoxia for 14 days. Exposure to hyperoxia induced the well-known features of BPD-PH such as elevated right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling and decreased pulmonary vascular density. Intrapulmonary arteries from hyperoxic pups showed decreased endothelium-dependent relaxation to acetylcholine without any alteration of relaxation to the NO-donor sodium nitroprusside. This functional alteration was associated with a decrease of lung eNOS phosphorylation at the Ser1177 activating site. In pups exposed to hyperoxia, serotonin and phenylephrine induced exacerbated contractile responses of intrapulmonary arteries as well as intracellular calcium response in pulmonary arterial smooth muscle cells (PASMC. Moreover, the amplitude of the store-operated Ca2+ entry (SOCE, induced by store depletion using a SERCA inhibitor, was significantly greater in PASMC from hyperoxic pups. Altogether, hyperoxia-induced BPD-PH alters the pulmonary arterial reactivity, with effects on both endothelial and smooth muscle functions. Reduced activating eNOS phosphorylation and enhanced Ca2+ signaling likely account for alterations of pulmonary arterial reactivity.

  1. Altered vasoreactivity in neonatal rats with pulmonary hypertension associated with bronchopulmonary dysplasia: Implication of both eNOS phosphorylation and calcium signaling.

    Science.gov (United States)

    Dumas de la Roque, Eric; Smeralda, Gwladys; Quignard, Jean-François; Freund-Michel, Véronique; Courtois, Arnaud; Marthan, Roger; Muller, Bernard; Guibert, Christelle; Dubois, Mathilde

    2017-01-01

    Bronchopulmonary dysplasia (BPD) consists of an arrest of pulmonary vascular and alveolar growth, with persistent hypoplasia of the pulmonary microvasculature and alveolar simplification. In 25 to 40% of the cases, BPD is complicated by pulmonary hypertension (BPD-PH) that significantly increases the risk of morbidity. In vivo studies suggest that increased pulmonary vascular tone could contribute to late PH in BPD. Nevertheless, an alteration in vasoreactivity as well as the mechanisms involved remain to be confirmed. The purpose of this study was thus to assess changes in pulmonary vascular reactivity in a murine model of BPD-PH. Newborn Wistar rats were exposed to either room air (normoxia) or 90% O2 (hyperoxia) for 14 days. Exposure to hyperoxia induced the well-known features of BPD-PH such as elevated right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling and decreased pulmonary vascular density. Intrapulmonary arteries from hyperoxic pups showed decreased endothelium-dependent relaxation to acetylcholine without any alteration of relaxation to the NO-donor sodium nitroprusside. This functional alteration was associated with a decrease of lung eNOS phosphorylation at the Ser1177 activating site. In pups exposed to hyperoxia, serotonin and phenylephrine induced exacerbated contractile responses of intrapulmonary arteries as well as intracellular calcium response in pulmonary arterial smooth muscle cells (PASMC). Moreover, the amplitude of the store-operated Ca2+ entry (SOCE), induced by store depletion using a SERCA inhibitor, was significantly greater in PASMC from hyperoxic pups. Altogether, hyperoxia-induced BPD-PH alters the pulmonary arterial reactivity, with effects on both endothelial and smooth muscle functions. Reduced activating eNOS phosphorylation and enhanced Ca2+ signaling likely account for alterations of pulmonary arterial reactivity.

  2. Triclosan alterations of estuarine phytoplankton community structure.

    Science.gov (United States)

    Pinckney, James L; Thompson, Laura; Hylton, Sarah

    2017-06-15

    Antimicrobial additives in pharmaceutical and personal care products are a major environmental concern due to their potential ecological impacts on aquatic ecosystems. Triclosan (TCS) has been used as an antiseptic, disinfectant, and preservative in various media. The sublethal and lethal effects of TCS on estuarine phytoplankton community composition were investigated using bioassays of natural phytoplankton communities to measure phytoplankton responses to different concentrations of TCS ranging from 1 to 200μgl -1 . The EC 50 (the concentration of an inhibitor where the growth is reduced by half) for phytoplankton groups (diatoms, chlorophytes, cryptophytes) examined in this ranged from 10.7 to 113.8μg TCS l -1 . Exposures resulted in major shifts in phytoplankton community composition at concentrations as low as 1.0μg TCS l -1 . This study demonstrates estuarine ecosystem sensitivity to TCS exposure and highlights potential alterations in phytoplankton community composition at what are typically environmental concentrations of TCS in urbanized estuaries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Altered permeability barrier structure in cholesteatoma matrix

    DEFF Research Database (Denmark)

    Svane-Knudsen, Viggo; Halkier-Sørensen, Lars; Rasmussen, Gurli

    2002-01-01

    lipid structures filling the intercellular spaces mainly control the barrier function. The barrier in cholesteatoma epithelium is several times thicker than in unaffected skin but presents distinctive features of a defective barrier as seen in other scaling skin diseases. The intercellular spaces appear...... frequently occur. The corneocytes are shed in clusters, not as single cells. Further, lipid droplets and intracellular membranous material are occasionally seen. In spite of these clear signs of barrier dysfunction, it is unknown whether the thickness of the barrier compensates for the defect in barrier...

  4. Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy.

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Pérez-Gil, Jesús

    2014-06-01

    Pulmonary surfactant is an essential lipid-protein complex to maintain an operative respiratory surface at the mammalian lungs. It reduces surface tension at the alveolar air-liquid interface to stabilise the lungs against physical forces operating along the compression-expansion breathing cycles. At the same time, surfactant integrates elements establishing a primary barrier against the entry of pathogens. Lack or deficiencies of the surfactant system are associated with respiratory pathologies, which treatment often includes supplementation with exogenous materials. The present review summarises current models on the molecular mechanisms of surfactant function, with particular emphasis in its biophysical properties to stabilise the lungs and the molecular alterations connecting impaired surfactant with diseased organs. It also provides a perspective on the current surfactant-based strategies to treat respiratory pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Rare earth impact on glass structure and alteration kinetics

    International Nuclear Information System (INIS)

    Molieres, E.

    2012-01-01

    This work is related to the question of the geological deep repository of high-level waste glass. These wastes include fission products and minor actinides, elements which can be simulated by rare earths. As new glass compositions could enable increased rare earth concentrations, it is crucial to know and understand rare earth impact on glass structure on the one hand, and on glass alteration kinetics or their incorporation into an altered layer. This work studied simplified borosilicate glasses in order to limit synergetic effects between rare earths and other elements. Various complementary techniques were used to characterize pristine and altered glasses (solid-high resolution NMR, Raman spectroscopy, fluorescence, SIMS, SAXS). Firstly, the structural role of a rare earth is discussed and is compared to a calcium cation. The local environment of rare earths is also probed. Secondly, rare earth (nature and concentration) impact on several alteration regimes was studied (initial rate, rate drop). Then, after alteration, rare earth elements being retained within the altered layer, the structural impact of rare earth elements (and their local environment) in this alteration layer was also investigated. (author) [fr

  6. Structural and functional characteristics of peripheral pulmonary parenchyma in golden hamsters.

    Science.gov (United States)

    Sata, M; Takahashi, K; Sato, S; Tomoike, H

    1995-01-01

    Mechanical properties of the peripheral pulmonary parenchyma of freshly excised hamster lung tissue were examined to evaluate determinants of displacement-tension relationships with regard to structural constituents of the alveolar wall. A tissue segment measuring 50 x 50 x 400-600 microns and consisting mostly of the alveolar wall was prepared from the lung parenchyma adjacent to the pleura. By use of a constant speed maneuver for extension and relaxation of this minute preparation, displacement-tension relationships of peripheral pulmonary parenchyma were examined in a bath filled with 37 degrees C physiological buffer solution. The specimen was repeatedly extended up to 20-40 mg, a little above a point resembling "yield" in displacement-tension relationships. Analyses of displacement-tension relationships constantly showed double exponential relations. The first component at the lower strain was approximated by sigma 1 = A1(e alpha 1 epsilon - 1) and the second component beyond the inflection (yield) point was sigma = s1 + s2 = A1(e alpha 1 epsilon - 1) + A2(e alpha 2 epsilon - 1), where sigma, A, alpha, and epsilon represent stress, constant determined by tissue quantity, elasticity constant, and strain, respectively. Immersion of the lung specimen into elastase resulted in decreases of only alpha 1, and collagenase reduced alpha 2 but not alpha 1. Hyaluronidase, acetylcholine, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and norepinephrine did not alter alpha 1 or alpha 2. These observations suggest that alpha 1 and alpha 2 of the peripheral pulmonary parenchyma are mechanical indexes of elastin and collagen characters, respectively.

  7. Epidermal growth factor receptor structural alterations in gastric cancer

    International Nuclear Information System (INIS)

    Moutinho, Cátia; Mateus, Ana R; Milanezi, Fernanda; Carneiro, Fátima; Seruca, Raquel; Suriano, Gianpaolo

    2008-01-01

    EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the EGFR gene in a series of primary gastric carcinomas. Direct sequencing of the kinase domain of the EGFR gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between EGFR alterations and the clinical pathological features of the tumours were performed. Within the 77 primary gastric carcinomas we found two EGFR somatic mutations and several EGFR polymorphisms in exon 20. Six different intronic sequence variants of EGFR were also found. Four gastric carcinomas showed balanced polysomy or EGFR gene amplification. We verified that gastric carcinoma with alterations of EGFR (somatic mutations or copy number variation) showed a significant increase of tumour size (p = 0.0094) in comparison to wild-type EGFR carcinomas. We demonstrate that EGFR structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for EGFR alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors

  8. Altered microRNA Signatures in Sputum of Patients with Active Pulmonary Tuberculosis

    OpenAIRE

    Yi, Zhengjun; Fu, Yurong; Ji, Rui; Li, Ruifang; Guan, Zhiyu

    2012-01-01

    Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differenti...

  9. Interrelation between Alterations in Pulmonary Mechanics and hemodynamics in Acute Myocardial Infarction

    Science.gov (United States)

    Interiano, Benjamin; Hyde, Richard W.; Hodges, Morrison; Yu, Paul N.

    1973-01-01

    Pulmonary mechanics were evaluated in 30 patients with acute myocardial infarction by measuring forced expiratory flow rates and total pulmonary resistance (RT) with the oscillometric method at the resonant frequency of the chest (6-8) cycle/s). During the first 3 days after infarction, forced expiratory volume (FEV) and forced mid-expiratory flow rate (FEF25-75%) were 69% and 60% of predicted values, respectively. 10 or more wk later these values were 95% and 91%. Initially, RT was 52% greater than predicted, but was only 4% greater 10 or more wk later. In 11 patients RT was measured at both resonant frequency and at 3 cycle/s. Five of these patients had no clinical signs of heart failure, but nine had abnormally high values of pulmonary artery pressure, “wedge” pressure and pulmonary extravascular water volume. All of these patients recovered. Initially, RT at resonance was 50% and RT at 3 cycle/s was 130% greater than predicted values. 2-3 wk later these figures were -3% and +6% of those predicted, respectively. At 10 wk or more, significant frequency dependence of RT had disappeared (RT at 3 cycle/s was 7% greater than RT at resonance). Isoproterenol inhalation in six patients caused no change in flow rates, RT at resonance, or RT at 3 cycle/s. RT at resonance and at 3 cycle/s, FEV, and FEF25-75% correlated significantly with the pulmonary vascular pressures. Patients with more marked arterial hypoxia and larger values for extravascular water volume had greater elevations of RT and depression of FEF25-75%, but linear correlations were not significant. Clinical signs of congestive heart failure significantly correlated with a fall in FEV and FEF25-75%, the development of frequency dependence of RT, and elevation of the pulmonary wedge pressure. The initial elevation of RT and low flow rates indicate a modest degree of airway obstruction in acute myocardial infarction. Lack of response to isoproterenol suggests that bronchial muscular constriction is not a

  10. Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema by altering Tie2 expression.

    Science.gov (United States)

    Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Lu, Yongbo; Juan, Aimee M; Chen, Jing; Mammoto, Akiko

    2013-01-01

    Tight regulation of vascular permeability is necessary for normal development and deregulated vascular barrier function contributes to the pathogenesis of various diseases, including acute respiratory distress syndrome, cancer and inflammation. The angiopoietin (Ang)-Tie2 pathway is known to control vascular permeability. However, the mechanism by which the expression of Tie2 is regulated to control vascular permeability has not been fully elucidated. Here we show that transcription factor Twist1 modulates pulmonary vascular leakage by altering the expression of Tie2 in a context-dependent way. Twist1 knockdown in cultured human lung microvascular endothelial cells decreases Tie2 expression and phosphorylation and increases RhoA activity, which disrupts cell-cell junctional integrity and increases vascular permeability in vitro. In physiological conditions, where Ang1 is dominant, pulmonary vascular permeability is elevated in the Tie2-specific Twist1 knockout mice. However, depletion of Twist1 and resultant suppression of Tie2 expression prevent increase in vascular permeability in an endotoxin-induced lung injury model, where the balance of Angs shifts toward Ang2. These results suggest that Twist1-Tie2-Angs signaling is important for controlling vascular permeability and modulation of this mechanism may lead to the development of new therapeutic approaches for pulmonary edema and other diseases caused by abnormal vascular permeability.

  11. Type 2 diabetes mellitus is associated with altered CD8+ T and natural killer cell function in pulmonary tuberculosis

    Science.gov (United States)

    Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash

    2015-01-01

    Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4+ T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8+ T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8+ T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8+ T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8+ T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8+ T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8+ T and NK cells, possibly contributing to increased pathology. PMID:25363329

  12. Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis.

    Science.gov (United States)

    Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash

    2015-04-01

    Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4(+) T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8(+) T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8(+) T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8(+) T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8(+) T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8(+) T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8(+) T and NK cells, possibly contributing to increased pathology. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  13. Altered Resting Brain Function and Structure in Professional Badminton Players

    Science.gov (United States)

    Di, Xin; Zhu, Senhua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan

    2012-01-01

    Abstract Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills. PMID:22840241

  14. Structural Alterations of the Glomerular Wall And Vessels in Early ...

    African Journals Online (AJOL)

    Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study. ... The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, ...

  15. Thoracic gunshot wounds: alterations to pulmonary function and respiratory muscle strength.

    Science.gov (United States)

    Baydur, Ahmet; Inaba, Kenji; Barmparas, Galinos; Teixeira, Pedro; Julianne, Awrey; Bukur, Marko; Talving, Peep; Demetriades, Demetrios

    2010-10-01

    The impact on respiratory function of gunshot injuries to the chest is unknown. The objective is to assess pulmonary function and respiratory muscle strength (RMS) in patients who have recently sustained an isolated gunshot injury to the chest. After institutional review board approval, patients with isolated gunshot injuries to the chest were prospectively identified. Study patients underwent pulmonary function testing and an assessment of RMS and gas exchange. Ten male patients sustaining an isolated pulmonary gunshot wound were prospectively enrolled with a mean age of 29 years ± 10 years and mean Injury Severity Score of 15 ± 5. All patients had an associated pneumothorax (n = 1), hemothorax (n = 4), or a combination of both (n = 5). After removal of all thoracostomy tubes and before discharge [7.4 days ± 5.4 days (range, 2-21 days)], patients underwent respiratory function testing. Lung volume subdivisions were reduced by 25% to 60% of predicted and diffusion capacity by 37% with preservation of the normal ratio of diffusion capacity to alveolar volume. In the six subjects able to perform spirometry in seated and supine postures, forced vital capacity decreased by 20% when changing posture (p = 0.046). Arterial blood gas analysis showed significant reduction in the P(AO)₂/FIO₂ ratio (or increase in AaDO₂). Maximal respiratory pressures were severely reduced from predicted values, the maximal inspiratory pressure by 60% and the maximal expiratory pressure by 78%. Lung volumes and RMS are decreased moderately to severely in patients who have sustained an isolated pulmonary gunshot wound. Expiratory muscle force generation is more severely affected than inspiratory muscle force. Further investigation of the long-term impact of these injuries on respiratory function is warranted.

  16. [Altered expressions of alkane monooxygenase and hypoxia inducible factor-1α expression in lung tissue of rat hypoxic pulmonary hypertension].

    Science.gov (United States)

    Deng, Hua-jun; Yuan, Ya-dong

    2013-10-29

    To explore the altered expressions of alkane monooxygenase (AlkB) and hypoxia-inducible factor-1α (HIF-1α) in a rat model of hypoxic pulmonary arterial hypertension. Twenty Wistar rats were divided randomly into normal control and hypoxia groups after 1-week adaptive feeding. Hypoxia group was raised in a homemade organic glass tank with a 24-h continuous supply of air and nitrogen atmospheric mixed gas. And the oxygen concentration of (10.0 ± 0.5)% was controlled by oxygen monitoring control system. The control group was maintained in room air. Both groups stayed in the same room with the same diet. After 8 weeks, the level of mean pulmonary pressure (mPAP) was measured by right-heart catheterization, right ventricular hypertrophy index (RVHI) calculated by the ratio of right ventricle to left ventricle plus septum and hypoxic pulmonary vascular remodeling (HPSR) observed under microscope. And the levels of AlkB and HIF-1α mRNA and protein in lungs were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. At 8 weeks post-hypoxia, compared with the control group [11.0 ± 0.7 mm Hg (1 mm Hg = 0.133 kPa), 0.210 ± 0.035], the levels of mPAP and RVHI in hypoxia group (33.3 ± 1.3 mm Hg, 0.448 ± 0.013) increased significantly (both P < 0.05), the expressions of AlkB mRNA and protein in pulmonary tissue decreased significantly (0.338 ± 0.085 vs 0.688 ± 0.020, P < 0.01) (0.483 ± 0.052 vs 0.204 ± 0.010, P < 0.01), and the expressions of HIF-1α mRNA and protein increased significantly (0.790 ± 0.161 vs 0.422 ± 0.096, P < 0.01) (0.893 ± 0.080 vs 0.346 ± 0.008, P < 0.01). The down-regulation of AlkB in lung tissue may increase the activity of HIF-1 to participate in the occurrence and development of pulmonary hypertension.

  17. Acacia hydaspica R. Parker ameliorates cisplatin induced oxidative stress, DNA damage and morphological alterations in rat pulmonary tissue.

    Science.gov (United States)

    Afsar, Tayyaba; Razak, Suhail; Almajwal, Ali; Khan, Muhammad Rashid

    2018-02-02

    Cisplatin (CP) drug is platinum compounds used for the treatment of various human malignancies. However, adverse outcomes related to CP restrict its usage. Acacia hydaspica is a natural shrub with various pharmacological properties. The current investigation aimed to assess the protective potential of A. hydaspica polyphenol rich ethyl acetate extract (AHE) against cisplatin (CP) induced pulmonary toxicity. Rats were divided into six groups. Group 1 served as control (saline); Group 2 (drug control) recieved single dose of CP (7.5 mg/kg i.p.) on 1st day; Group 3 (extract control) (400 mg/kg bw, p.o.) received AHE for one week; Group 4 (Post-treated) and Group 5 (pretreated) received AHE (400 mg/kg bw/day, p.o) for 7 days after and before CP (7.5 mg/kg b.w., i.p.) respectively; Group 6 (Standard control) received silymarin (100 mg/kg b.w/7 days) before CP. At the end of dosing rats were sacrificed and pulmonary tissue samples were processed for the evaluation of antioxidant enzymes, oxidative stress markers, genotoxicity and histopathological alterations. CP caused body weights loss and increase pulmonary tissue weight. The CP significantly increases oxidative stress markers and decreases tissue antioxidant enzyme levels. Furthermore, CP induced deleterious changes in the microanatomy of pulmonary tissue by rupturing the alveolar septa, thickening of alveolar walls, and injuring the cells with subsequent collapse of blood vessels. AHE pretreatment returned MDA, NO, H 2 O 2 production and improved tissue antioxidant enzyme levels to near normalcy. The histological observations evidenced that AHE effectively rescues the lungs from CP-mediated oxidative damage. CP induction in rats also caused DNA fragmentation which was restored by AHE treatment. Our results suggest that pretreatment more significantly improve CP induced deleterious effects compared with post treatment indicating protective effect. Potency of AHE pretreatment is similar to silymarin. These

  18. Subclinical depressive symptoms during late midlife and structural brain alterations

    DEFF Research Database (Denmark)

    Osler, Merete; Sørensen, Lauge; Rozing, Maarten

    2018-01-01

    at age 51, 56, and 59 years, magnetic resonance imaging was performed at age 59. All data processing was performed using the Freesurfer software package except for the texture-scores that were computed using in-house software. Structural brain alterations and associations between depressive symptoms......We explored whether depressive symptoms measured three times during midlife were associated with structural brain alterations quantified using magnetic resonance imaging measurements of volume, cortical thickness, and intensity texture. In 192 men born in 1953 with depressive symptoms measured...... and brain structure outcomes were tested using Pearson's correlation, t test, and linear regression. Depressive symptoms at age 51 showed clear inverse correlations with total gray matter, pallidum, and hippocampal volume with the strongest estimate for hippocampal volume (r = -.22, p 

  19. Altered Pulmonary Artery Endothelial - Smooth Muscle Cell Interactions in Experimental Congenital Diaphragmatic Hernia

    Science.gov (United States)

    Acker, Shannon N.; Seedorf, Gregory J.; Abman, Steven H.; Nozik-Grayck, Eva; Kuhn, Katherine; Partrick, David A.; Gien, Jason

    2014-01-01

    Background Pulmonary hypertension (PH) secondary to vascular remodeling contributes to poor outcomes in congenital diaphragmatic hernia (CDH), however mechanisms responsible are unknown. We hypothesized that pulmonary artery endothelial cell (PAEC) dysfunction contributes to smooth muscle cell (SMC) hyperplasia in experimental CDH. Methods PAEC and SMC were isolated from fetal sheep with experimental CDH and controls. SMC growth was assessed alone and with SOD plus catalase and during co-culture with control or CDH PAEC with and without ET-1 siRNA transfection. ET-1 protein was measured in PAEC and PASMC lysates and supernatant. ROS production was measured in normal and CDH PAECs with and without ET-1 siRNA. PAEC growth and tube formation were measured with SOD plus catalase. Results CDH SMC growth was decreased and and increased with co-culture with CDH PAEC more than control PAEC. Treatment of CDH PAEC with SOD plus catalase or ET-1 siRNA prevented the increase in SMC growth seen with co-culture. ET-1 protein was increased in CDH PAEC and SMC. ROS production was increased in CDH PAEC and decreased with ET-1 SiRNA. SOD plus catalase restored CDH PAEC growth and tube formation. Conclusions PAEC dysfunction in experimental CDH increases SMC proliferation via ET-1 induced ROS production by PAEC. PMID:25580737

  20. Dietary vitamin E and pulmonary biochemical and morphological alterations of rats exposed to 0. 1 ppM ozone

    Energy Technology Data Exchange (ETDEWEB)

    Chow, C.K. (Univ. of Kentucky, Lexington); Plopper, C.G.; Chiu, M.; Dungworth, D.L.

    1981-04-01

    Three groups of 28 1-month-old male Sprague-Dawley rats each were fed a basal vitamin E-deficient diet and supplemented with either 0, 11, or 110 ppM vitamin E for 38 days, and were then exposed to 0 or 0.1 ppM ozone continuously for 7 days. Following ozone exposure, the level of reduced glutathione (GSH) and activities of GSH peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase (G-6-PD), and lactate dehydrogenase (LDH), but not of malic dehydrogenase, were significantly elevated in the lungs of rats fed the vitamin E deficient diet. The level of GSH and activities of GSH peroxidase and G-6-PD were also significantly increased in the lungs of the animal group fed the 11 ppM vitamin E diet, while none of the biochemical measurements made was significantly altered by ozone in the 110-ppM vitamin E diet fed rats. Scanning electron microscope examination revealed that five out of six rats on the vitamin E-deficient diet and four out of six from the 11-ppM vitamin E diet had detectable lesions following ozone exposure, as compared with only one of the six exposed animals from the 110-ppM vitamin E diet. The lesion was restricted to bronchiolar epithelium and alveoli immediately adjacent to the bronchiole-alveolar duct junction. None of the control animals had detectable lesions. The results suggest that exposure to ozone at 0.1-ppM level can produce detectable pulmonary damage, and that dietary vitamin E alters pulmonary susceptibility to ozone exposure.

  1. Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

    Directory of Open Access Journals (Sweden)

    J.H.T. Ferreira

    2006-09-01

    Full Text Available The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 ± 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 ± 8.64 to 39.14 ± 6.77 mmHg and alveolar air (from 92.97 ± 2.14 to 63.91 ± 8.27 mmHg. The effective alveolar ventilation exhibited a significant reduction (from 199.62 ± 42.01 to 84.34 ± 44.13 consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio also presented a significant reduction after embolization (from 0.96 ± 0.34 to 0.33 ± 0.17 fraction. The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 ± 1.71 to 60.76 ± 6.62 mmHg, but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 ± 1.22 to 23.15 ± 8.24 mmHg. Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 ± 1.36 to 37.61 ± 12.79 mmHg, as also did the calculated alveolar (from 56.38 ± 22.47 to 178.09 ± 37.46 mL and physiological (from 0.37 ± 0.05 to 0.75 ± 0.10 fraction dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution

  2. Local Reasoning about Programs that Alter Data Structures

    DEFF Research Database (Denmark)

    O'Hearn, Peter W.; Reynolds, John Clifton; Yang, Hongseok

    2001-01-01

    We describe an extension of Hoare's logic for reasoning about programs that alter data structures. We consider a low-level storage model based on a heap with associated lookup, update, allocation and deallocation operations, and unrestricted address arithmetic. The assertion language is based....... Through these and a number of examples we show that the formalism supports local reasoning: A speci-cation and proof can concentrate on only those cells in memory that a program accesses. This paper builds on earlier work by Burstall, Reynolds, Ishtiaq and O'Hearn on reasoning about data structures....

  3. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    Science.gov (United States)

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  4. Preterm birth and structural brain alterations in early adulthood

    Directory of Open Access Journals (Sweden)

    Chiara Nosarti

    2014-01-01

    Full Text Available Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM and white matter (WM maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001. WM volume in posterior corpus

  5. Altered structural brain changes and neurocognitive performance in pediatric HIV

    Directory of Open Access Journals (Sweden)

    Santosh K. Yadav

    2017-01-01

    Full Text Available Pediatric HIV patients often suffer with neurodevelopmental delay and subsequently cognitive impairment. While tissue injury in cortical and subcortical regions in the brain of adult HIV patients has been well reported there is sparse knowledge about these changes in perinatally HIV infected pediatric patients. We analyzed cortical thickness, subcortical volume, structural connectivity, and neurocognitive functions in pediatric HIV patients and compared with those of pediatric healthy controls. With informed consent, 34 perinatally infected pediatric HIV patients and 32 age and gender matched pediatric healthy controls underwent neurocognitive assessment and brain magnetic resonance imaging (MRI on a 3 T clinical scanner. Altered cortical thickness, subcortical volumes, and abnormal neuropsychological test scores were observed in pediatric HIV patients. The structural network connectivity analysis depicted lower connection strengths, lower clustering coefficients, and higher path length in pediatric HIV patients than healthy controls. The network betweenness and network hubs in cortico-limbic regions were distorted in pediatric HIV patients. The findings suggest that altered cortical and subcortical structures and regional brain connectivity in pediatric HIV patients may contribute to deficits in their neurocognitive functions. Further, longitudinal studies are required for better understanding of the effect of HIV pathogenesis on brain structural changes throughout the brain development process under standard ART treatment.

  6. Altered distribution of peripheral blood dendritic cell subsets in patients with pulmonary paracoccidioidomycosis.

    Science.gov (United States)

    Venturini, James; Cavalcante, Ricardo Souza; Moris, Daniela Vanessa; Golim, Márjorie de Assis; Levorato, Adriele Dandara; Reis, Karoline Hagatha Dos; Arruda, Maria Sueli Parreira de; Mendes, Rinaldo Poncio

    2017-09-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi from the genus Paracoccidioides in Latin America. PCM-patients (PCM-p) are classified as having acute/subacute or chronic (CF) clinical forms. CF is responsible for 75%-90% of all cases, affects mainly adults over 30 years old and the clinical manifestation are associated mainly with lungs and mucosa of upper airdigestive tract. In addition, the CF patients exhibit fibrosis of the lungs, oral mucous membranes and adrenals, and pulmonary emphysema. Consequently, CF PCM-p with active disease, as well as those that have been apparently cured, seem to be an interesting model for studies aiming to understand the long-term host-fungi relationship and hypoxia. Dendritic cells (DCs) constitute a system that serve as a major link between innate and adaptive immunity composed of several subpopulations of cells including two main subsets: myeloid (mDCs) and plasmacytoid (pDCs). The present study aimed to access the distribution of PBDC subsets of CF PCM-p who were not treated (NT) or treated (apparently cured - AC). CF PCM-p were categorized into two groups, consisting of 9 NTs and 9 ACs. Twenty-one healthy individuals were used as the control group. The determination of the PBDC subsets was performed by FACS (fluorescence-activated cell sorting) and the dosage of serum TNF-α, IL1β, IL-18, CCL3, IL-10 and basic fibroblast growth factor (bFGF) by ELISA (enzyme-linked immunosorbent assay). A high count and percentage of mDCs was observed before treatment, along with a low count of pDCs in treated patients. Furthermore, the mDC:pDC ratio and serum levels of TNF-α was higher in both of the PCM-p groups than in the control group. In conclusion, our findings demonstrated that active PCM influences the distribution of mDCs and pDCs, and after treatment, PCM-p retained a lower count of pDCs associated with pro-inflammatory profile. Therefore, we identified new evidences of persistent immunological abnormalities in

  7. Phenotype- and genotype-specific structural alterations in spasmodic dysphonia.

    Science.gov (United States)

    Bianchi, Serena; Battistella, Giovanni; Huddleston, Hailey; Scharf, Rebecca; Fleysher, Lazar; Rumbach, Anna F; Frucht, Steven J; Blitzer, Andrew; Ozelius, Laurie J; Simonyan, Kristina

    2017-04-01

    Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology. Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes). Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus. Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  8. Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD

    Directory of Open Access Journals (Sweden)

    Bjoern Titz

    2016-09-01

    Full Text Available Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD. To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD—and to support future biomarker development—we profiled the serum lipidomes of healthy smokers, smokers with mild to moderate COPD (GOLD stages 1 and 2, former smokers, and never-smokers (n = 40 per group (ClinicalTrials.gov registration: NCT01780298. Serum lipidome profiling was conducted with untargeted and targeted mass spectrometry-based lipidomics. Guided by weighted lipid co-expression network analysis, we identified three main trends comparing smokers, especially those with COPD, with non-smokers: a general increase in glycero(phospholipids, including triglycerols; changes in fatty acid desaturation (decrease in ω-3 polyunsaturated fatty acids, and an increase in monounsaturated fatty acids; and an imbalance in eicosanoids (increase in 11,12- and 14,15-DHETs (dihydroxyeicosatrienoic acids, and a decrease in 9- and 13-HODEs (hydroxyoctadecadienoic acids. The lipidome profiles supported classification of study subjects as smokers or non-smokers, but were not sufficient to distinguish between smokers with and without COPD. Overall, our study yielded further insights into the complex interplay between smoke exposure, lung disease, and systemic alterations in serum lipid profiles.

  9. Structural brain alterations associated with dyslexia predate reading onset.

    Science.gov (United States)

    Raschle, Nora Maria; Chang, Maria; Gaab, Nadine

    2011-08-01

    Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals with developmental dyslexia have been complemented by reports of reduced gray matter in left parietotemporal, occipitotemporal areas, fusiform and lingual gyrus and the cerebellum. An important question for education is whether these neural differences are present before reading is taught. Developmental dyslexia can only be diagnosed after formal reading education starts. However, here we investigate whether the previously detected gray matter alterations in adults and children with developmental dyslexia can already be observed in a small group of pre-reading children with a family-history of developmental dyslexia compared to age and IQ-matched children without a family-history (N = 20/mean age: 5:9 years; age range 5:1-6:5 years). Voxel-based morphometry revealed significantly reduced gray matter volume indices for pre-reading children with, compared to children without, a family-history of developmental dyslexia in left occipitotemporal, bilateral parietotemporal regions, left fusiform gyrus and right lingual gyrus. Gray matter volume indices in left hemispheric occipitotemporal and parietotemporal regions of interest also correlated positively with rapid automatized naming. No differences between the two groups were observed in frontal and cerebellar regions. This discovery in a small group of children suggests that previously described functional and structural alterations in developmental dyslexia may not be due to experience-dependent brain changes but may be present at birth or

  10. Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Anguel N Stefanov

    Full Text Available Pulmonary fibrosis is a disease of significant morbidity, with no effective therapeutics and an as yet incompletely defined genetic basis. The chemotherapeutic agent bleomycin induces pulmonary fibrosis in susceptible C57BL/6J mice but not in mice of the C3H/HeJ strain, and this differential strain response has been used in prior studies to map bleomycin-induced pulmonary fibrosis susceptibility loci named Blmpf1 and Blmpf2. In this study we isolated the quantitative trait gene underlying Blmpf2 initially by histologically phenotyping the bleomycin-induced lung disease of sublines of congenic mice to reduce the linkage region to 13 genes. Of these genes, Trim16 was identified to have strain-dependent expression in the lung, which we determined was due to sequence variation in the promoter. Over-expression of Trim16 by plasmid injection increased pulmonary fibrosis, and bronchoalveolar lavage levels of both interleukin 12/23-p40 and neutrophils, in bleomycin treated B6.C3H-Blmpf2 subcongenic mice compared to subcongenic mice treated with bleomycin only, which follows the C57BL/6J versus C3H/HeJ strain difference in these traits. In summary we demonstrate that genetic variation in Trim16 leads to its strain-dependent expression, which alters susceptibility to bleomycin-induced pulmonary fibrosis in mice.

  11. Altered osteoblast structure and function in parabolic flight

    Science.gov (United States)

    Zhong-Quan, Dai; Ying-Hui, Li; Fen, Yang; Bai, Ding; Ying-Jun, Tan

    Introduction Bone loss has a significant impact on astronauts during spaceflight being one of the main obstacles preventing interplanetary missions However the exact mechanism is not well understood In the present study we investigated the effects of acute gravitational changes generated by parabolic flight on the structure and function of osteoblasts ROS17 2 8 carried by airbus A300 Methods The alteration of microfilament cytoskeleton was observed by the Texas red conjugated Phalloidin and Alexa Fluor 488 conjugated DNase I immunofluorescence stain ALP activity and expression COL1A1 expression osteocalcin secrete which presenting the osteoblast function were detected by modified calcium and cobalt method RT-PCR and radioimmunity methods respectively Results The changed gravity induced the reorganization of microfilament cytoskeleton of osteoblast After 3 hours parabolic flight F-actin of osteoblast cytoskeleton became more thickness and directivity whereas G-actin reduced and relatively concentrated at the edge of nucleus observed by confocal fluorescence microscopy This phenomenon is identical with structure alternation observed in hypergravity but the osteoblast function decrease The excretion of osteocalcin the activity and mRNA expression of ALP decrease but the COL1A1 expression has no changes These results were similar to the changes in simulated or real microgravity Conclusion Above results suggest that short time gravity alternative change induce osteoblast structure and function

  12. Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis

    Science.gov (United States)

    Madala, Satish K.; Korfhagen, Thomas R.; Schmidt, Stephanie; Davidson, Cynthia; Edukulla, Ramakrishna; Ikegami, Machiko; Violette, Shelia M.; Weinreb, Paul H.; Sheppard, Dean

    2014-01-01

    A number of growth factors and signaling pathways regulate matrix deposition and fibroblast proliferation in the lung. The epidermal growth factor receptor (EGFR) family of receptors and the transforming growth factor-β (TGF-β) family are active in diverse biological processes and are central mediators in the initiation and maintenance of fibrosis in many diseases. Transforming growth factor-α (TGF-α) is a ligand for the EGFR, and doxycycline (Dox)-inducible transgenic mice conditionally expressing TGF-α specifically in the lung epithelium develop progressive fibrosis accompanied with cachexia, changes in lung mechanics, and marked pleural thickening. Although recent studies demonstrate that EGFR activation modulates the fibroproliferative effects involved in the pathogenesis of TGF-β induced pulmonary fibrosis, in converse, the direct role of EGFR induction of the TGF-β pathway in the lung is unknown. The αvβ6 integrin is an important in vivo activator of TGF-β activation in the lung. Immunohistochemical analysis of αvβ6 protein expression and bronchoalveolar analysis of TGF-β pathway signaling indicates activation of the αvβ6/TGF-β pathway only at later time points after lung fibrosis was already established in the TGF-α model. To determine the contribution of the αvβ6/TGF-β pathway on the progression of established fibrotic disease, TGF-α transgenic mice were administered Dox for 4 wk, which leads to extensive fibrosis; these mice were then treated with a function-blocking anti-αvβ6 antibody with continued administration of Dox for an additional 4 wk. Compared with TGF-α transgenic mice treated with control antibody, αvβ6 inhibition significantly attenuated pleural thickening and altered the decline in lung mechanics. To test the effects of genetic loss of the β6 integrin, TGF-α transgenic mice were mated with β6-null mice and the degree of fibrosis was compared in adult mice following 8 wk of Dox administration. Genetic ablation of

  13. Pulmonary vascular abnormalities in chronic obstructive pulmonary disease undergoing lung transplant.

    Science.gov (United States)

    Peinado, Victor I; Gómez, Federico P; Barberà, Joan Albert; Roman, Antonio; Angels Montero, M; Ramírez, Josep; Roca, Josep; Rodriguez-Roisin, Roberto

    2013-12-01

    Little is known about the structure and function relationships of pulmonary vessels in the most severe chronic obstructive pulmonary disease (COPD) spectrum. We investigated morphometric, cellular, and physiologic characteristics of pulmonary arteries from COPD patients undergoing bilateral lung transplant. Seventeen patients with very severe COPD (forced expiratory volume in 1 second, 24% ± 7%) were assessed using inert gas exchange and pulmonary hemodynamics while breathing ambient air and 100% oxygen. Morphometry, in vitro reactivity to hypoxia, and inflammatory cell counts of pulmonary arteries were measured in explanted lungs. Patients had moderate ventilation-perfusion imbalance along with mild release of hypoxic pulmonary vasoconstriction. Mild pulmonary hypertension was observed in 7 patients. Explanted lungs had predominant emphysema with mild small airway involvement. In vitro reactivity was modestly altered, with relatively preserved endothelium-dependent relaxation, and vascular remodelling was discrete, with intense CD8+ T lymphocytes infiltrate. In vitro reactivity correlated with pulmonary vascular resistance (on ambient air) and oxygen-induced pulmonary artery pressure changes. Patients with pulmonary hypertension had more severe morphologic and physiologic emphysema. In end-stage COPD patients undergoing lung transplant, pulmonary vascular involvement is unexpectedly modest, with low-grade endothelial dysfunction. In this sub-set of COPD patients, pulmonary emphysema may constitute the major determinant of the presence of pulmonary hypertension. © 2013 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.

  14. Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

    OpenAIRE

    Wolf, Lisa; Herr, Christian; Niederstra?er, Julia; Beisswenger, Christoph; Bals, Robert

    2017-01-01

    The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decrease...

  15. Addition of electrophilic lipids to actin alters filament structure

    International Nuclear Information System (INIS)

    Gayarre, Javier; Sanchez, David; Sanchez-Gomez, Francisco J.; Terron, Maria C.; Llorca, Oscar; Perez-Sala, Dolores

    2006-01-01

    Pathophysiological processes associated with oxidative stress lead to the generation of reactive lipid species. Among them, lipids bearing unsaturated aldehyde or ketone moieties can form covalent adducts with cysteine residues and modulate protein function. Through proteomic techniques we have identified actin as a target for the addition of biotinylated analogs of the cyclopentenone prostaglandins 15-deoxy-Δ 12,14 -PGJ 2 (15d-PGJ 2 ) and PGA 1 in NIH-3T3 fibroblasts. This modification could take place in vitro and mapped to the protein C-terminal end. Other electrophilic lipids, like the isoprostane 8-iso-PGA 1 and 4-hydroxy-2-nonenal, also bound to actin. The C-terminal region of actin is important for monomer-monomer interactions and polymerization. Electron microscopy showed that actin treated with 15d-PGJ 2 or 4-hydroxy-2-nonenal formed filaments which were less abundant and displayed shorter length and altered structure. Streptavidin-gold staining allowed mapping of biotinylated 15d-PGJ 2 at sites of filament disruption. These results shed light on the structural implications of actin modification by lipid electrophiles

  16. The structure of alteration layers on cast glass surfaces

    International Nuclear Information System (INIS)

    Oversby, V.M.; Phinney, D.L.

    1991-11-01

    Alteration layers developed on SRL-165 simulated waste glasses in dilute sodium silicate/bicarbonate leaching solutions have been examined by Secondary Ionization Mass Spectroscopy (SIMS) using fine-scale, multiple-element depth profiling. Selected samples were examined with an imaging detector system, which demonstrated the horizontal homogeneity of the layer development at all depths within the layer. After 1 day of reaction at 90 degrees C the reaction layer shows depletion of glass elements to a depth of 0.2 μm. The surface of the layer in contact with the solution shows enrichment of Si, Al, and alkali elements even at this short reaction time, suggesting the early stages of development of secondary aluminosilicate phases. With increased reaction time, the layer thickens to about 1.3 μm at 91 days, while the evidence for aluminosilicate development at the surface of the layer becomes more prominent. Penetration of hydrogen into the ''unreacted'' glass proceeds to a depth of about 0.5 μm deeper than the alkali depletion zone. This suggests the mechanism of initial reaction of the glass is by attack of the silicate structure by molecular water or hydroxide ion rather than by alkali-hydrogen ion exchange. The simple structure of the layers developed in the silicate solution is in contrast to the complexity of layer structure found when glasses are reacted in deionized water. Since the conditions for geologic disposal will be closer to those used in the silicate leaching experiments, these results hold promise for the ability to model the system to predict long-term performance after disposal in a repository

  17. Structural equation modeling for alteration of occlusal plane inclination.

    Science.gov (United States)

    Shigeta, Yuko; Ogawa, Takumi; Nakamura, Yoshiharu; Ando, Eriko; Hirabayashi, Rio; Ikawa, Tomoko

    2015-07-01

    Occlusal plane inclination is important to maintain a normal opening closing/biting function. However, there can be several causes that lead to alterations of the occlusal plane. The purpose of this study was to observe variations of occlusal plane inclination in adult patients, and to uncover the factors affecting changes in occlusal plane inclination with aging. Subjects were 143 patients. A cephalometric image was taken of these patients. In this study, our inquiry points were age, 3 variables on intra-oral findings, and 7 variables on cephalometric analysis. To evaluate the possible causes that affect occlusal plane inclination, factor analysis was carried out, and each component was treated as factors, which were then statistically applied to a structural equation model. Statistical analysis was carried out through the SPSS 20.0 (SPSS Inc., Chicago, USA). In all patients, Camper-occlusal plane angle (COA) ranged from -25.7 to -4.9° (Mean±SD: -6.4±5.36). In the 60 patients who had no missing teeth, COA ranged from -11.6 to -4.9° (Mean±SD: -3.3±3.31). From the results of the structural analysis, it was suggested that the occlusal plane changes to counter-clockwise (on the right lateral cephalograms) with aging. In this study, variations of occlusal plane inclination in adult patients were observed, and the factors affecting changes in occlusal plane inclination with aging were investigated via factor analysis. From our results, it was suggested that the mandibular morphology change and loss of teeth with aging influence occlusal plane inclination. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  18. Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats

    International Nuclear Information System (INIS)

    White, S.M.; Wagner, J.G.; Roth, R.A.

    1989-01-01

    To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. Treatment with PAS on Days 6-8 did not affect the lung injury but resulted in an attenuation of the pulmonary hypertensive response. Pulmonary platelet sequestration was also decreased in PAS-treated rats, yet the sequestration in the lungs of MCTP-treated rats that received PAS was significantly higher than that in the lungs of N,N-dimethylformamide (DMF) controls. MCTP-treated rats receiving control serum (CS) tended to sequester more 111In-labeled platelets than respective DMF controls, but this was not statistically significant. Blood platelet half-life was unaltered in rats receiving CS. When rats were treated similarly with MCTP and PAS and were killed at 18 days, the attenuation of the pulmonary hypertensive response previously described was not observed, and lung injury was more extensive than when CS was given. Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets

  19. Organizational structure for chronic heart failure and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Rinne, Seppo T; Liu, Chuan-Fen; Wong, Edwin S; Hebert, Paul L; Heidenreich, Paul; Bastian, Lori A; Au, David H

    2016-03-01

    In contrast to chronic heart failure (CHF), measures of quality of care for chronic obstructive pulmonary disease (COPD) are poor. Our objective was to examine differences in organizational structure available to support quality of care for patients with CHF and COPD. We performed 2 nationwide surveys exploring organizational structure for the management of CHF and COPD. We surveyed the chief of medicine and the chief of cardiology and pulmonary medicine at 120 Veterans Affairs facilities in the United States. Analogous questions about organizational structure that enhanced adherence to guideline-based care were compared between CHF and COPD surveys. We found large and notable differences in the organizational structure for disease management, with systematically less attention given to COPD than CHF. These differences were evident in multiple processes of care. Key differences included fewer facilities: having COPD clinics than CHF clinics (12.7% vs 50.8%; P organizational structure existed for COPD than CHF. Lack of organizational structure for COPD likely impedes an organization's abilities to encourage high-quality care and avoid recently implemented hospital readmission penalties. Our results suggest the need to develop a systematic approach for healthcare systems to provide essential organizational structure based on the burden of disease in the population.

  20. An alter-centric perspective on employee innovation: The importance of alters' creative self-efficacy and network structure.

    Science.gov (United States)

    Grosser, Travis J; Venkataramani, Vijaya; Labianca, Giuseppe Joe

    2017-09-01

    While most social network studies of employee innovation behavior examine the focal employees' ("egos'") network structure, we employ an alter-centric perspective to study the personal characteristics of employees' network contacts-their "alters"-to better understand employee innovation. Specifically, we examine how the creative self-efficacy (CSE) and innovation behavior of employees' social network contacts affects their ability to generate and implement novel ideas. Hypotheses were tested using a sample of 144 employees in a U.S.-based product development organization. We find that the average CSE of alters in an employee's problem solving network is positively related to that employee's innovation behavior, with this relationship being mediated by these alters' average innovation behavior. The relationship between the alters' average innovation behavior and the employee's own innovation behavior is strengthened when these alters have less dense social networks. Post hoc results suggest that having network contacts with high levels of CSE also leads to an increase in ego's personal CSE 1 year later in cases where the employee's initial level of CSE was relatively low. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Patients with Chronic Obstructive Pulmonary Disease Walk with Altered Step Time and Step Width Variability as Compared with Healthy Control Subjects.

    Science.gov (United States)

    Yentes, Jennifer M; Rennard, Stephen I; Schmid, Kendra K; Blanke, Daniel; Stergiou, Nicholas

    2017-06-01

    Compared with control subjects, patients with chronic obstructive pulmonary disease (COPD) have an increased incidence of falls and demonstrate balance deficits and alterations in mediolateral trunk acceleration while walking. Measures of gait variability have been implicated as indicators of fall risk, fear of falling, and future falls. To investigate whether alterations in gait variability are found in patients with COPD as compared with healthy control subjects. Twenty patients with COPD (16 males; mean age, 63.6 ± 9.7 yr; FEV 1 /FVC, 0.52 ± 0.12) and 20 control subjects (9 males; mean age, 62.5 ± 8.2 yr) walked for 3 minutes on a treadmill while their gait was recorded. The amount (SD and coefficient of variation) and structure of variability (sample entropy, a measure of regularity) were quantified for step length, time, and width at three walking speeds (self-selected and ±20% of self-selected speed). Generalized linear mixed models were used to compare dependent variables. Patients with COPD demonstrated increased mean and SD step time across all speed conditions as compared with control subjects. They also walked with a narrower step width that increased with increasing speed, whereas the healthy control subjects walked with a wider step width that decreased as speed increased. Further, patients with COPD demonstrated less variability in step width, with decreased SD, compared with control subjects at all three speed conditions. No differences in regularity of gait patterns were found between groups. Patients with COPD walk with increased duration of time between steps, and this timing is more variable than that of control subjects. They also walk with a narrower step width in which the variability of the step widths from step to step is decreased. Changes in these parameters have been related to increased risk of falling in aging research. This provides a mechanism that could explain the increased prevalence of falls in patients with COPD.

  2. Diet-Induced Alterations in Gut Microflora Contribute to Lethal Pulmonary Damage in TLR2/TLR4-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Yewei Ji

    2014-07-01

    Full Text Available Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here, we show that chronic intake of a high-fat diet (HFD, not a low-fat diet, leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors 2 and 4 (DKO. Diet-induced pulmonary lesions are blocked by antibiotic treatment and are transmissible to wild-type mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut-microbiota-caused conditions are often life threatening.

  3. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films

    DEFF Research Database (Denmark)

    Ortiz, Elisa Parra; Perez-Gil, Jesús

    2015-01-01

    The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics of breath......The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics...... of breathing and avoiding alveolar collapse, especially at the end of expiration. The goal of the present review is to summarize current knowledge regarding the structure, lipid-protein interactions and mechanical features of surfactant membranes and films and how these properties correlate with surfactant...... biological function inside the lungs. Surfactant mechanical properties can be severely compromised by different agents, which lead to surfactant inhibition and ultimately contributes to the development of pulmonary disorders and pathologies in newborns, children and adults. A detailed comprehension...

  4. Analysis of the structure and surfactant activity of novel formulations containing exogenous pulmonary surfactant and glucocorticoids.

    Science.gov (United States)

    Cimato, Alejandra; Hoyos Obando, Andres; Facorro, Graciela; Martínez Sarrasague, María

    2016-11-01

    Exogenous pulmonary surfactant (EPS) could be used as carrier of glucocorticoids (GCs) in therapy for respiratory diseases. We formulated novel combination drug products containing bovine EPS and one GC (10wt%): beclomethasone (Be), budesonide (Bu) or fluticasone (Flu), and studied the GCs action on the surface activity and biophysical properties of EPS. Subtype ratio was evaluated by phospholipid determination; surface tension (ST) with a pulsating bubble surfactometer and conformational changes by Electron Spin Resonance (ESR). GCs were incorporated into EPS in more than 80%. None of them generated disaggregation of surfactant, only Bu was found in the light subtype. Bu and Be caused minimal changes in fluidity on polar region of bilayers, but these changes were not enough to inactivate the surfactant. Flu did not significantly alter any biophysical properties or surface activity. These novel combination EPS-GC products might be a promising strategy in the therapy of pulmonary diseases as the incorporation of the GCs tested did not cause detrimental effects on EPS functionality. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Surface based cardiac and respiratory motion extraction for pulmonary structures from multi-phase CT

    Science.gov (United States)

    von Berg, Jens; Barschdorf, Hans; Blaffert, Thomas; Kabus, Sven; Lorenz, Cristian

    2007-03-01

    During medical imaging and therapeutic interventions, pulmonary structures are in general subject to cardiac and respiratory motion. This motion leads potentially to artefacts and blurring in the resulting image material and to uncertainties during interventions. This paper presents a new automatic approach for surface based motion tracking of pulmonary structures and reports on the results for cardiac and respiratory induced motion. The method applies an active shape approach to ad-hoc generated surface representations of the pulmonary structures for phase to phase surface tracking. Input of the method are multi-phase CT data, either cardiac or respiratory gated. The iso-surface representing the transition between air or lung parenchyma to soft tissue, is triangulated for a selected phase p 0. An active shape procedure is initialised in the image of phase p I using the generated surface in p 0. The used internal energy term penalizes shape deformation as compared to p 0. The process is iterated for all phases p i to p i+1 of the complete cycle. Since the mesh topology is the same for all phases, the vertices of the triangular mesh can be treated as pseudo-landmarks defining tissue trajectories. A dense motion field is interpolated. The motion field was especially designed to estimate the error margins for radiotherapy. In the case of respiratory motion extraction, a validation on ten biphasic thorax CT images (2.5mm slice distance) was performed with expert landmarks placed at vessel bifurcations. The mean error on landmark position was below 2.6mm. We further applied the method to ECG gated images and estimated the influence of the heart beat on lung tissue displacement.

  6. Chronic obstructive pulmonary disease: getting it right. Does optimal management of chronic obstructive pulmonary disease alter disease progression and improve survival?

    Science.gov (United States)

    Russell, Richard E

    2014-03-01

    We live in a world where people live longer lives. The standardized mortality rate for many diseases is decreasing. Chronic obstructive pulmonary disease (COPD) is not following this trend. Over the last 10 years, interventions for COPD have been developed, but have any changed the prognosis or trajectory of this modern epidemic? We review the most recent and classical literature in order to answer this question. Recent analyses of data have clarified which interventions are effective in COPD and which are not. New studies have defined what is achievable with the current therapies. Only two interventions have been demonstrated to improve survival: smoking cessation and long-term oxygen therapy. Other treatments do reduce exacerbations, improve lung function and improve the patient's quality of life, but do not affect physiological disease progression or mortality. There is much work to do, not only to improve the treatments we have for this disease, but also to diagnose it early, intervene at the right time, reduce the treatment side-effects and most importantly understand the pathophysiology better. Moreover, we are duty bound to look at each patient and review what we are trying to achieve for each one through appropriate phenotyping as well as sometimes taking a more palliative approach.

  7. Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

    Directory of Open Access Journals (Sweden)

    Bastian Cheng

    2014-01-01

    Full Text Available Gilles de la Tourette syndrome (GTS is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico–striato–thalamo–cortical loops. We therefore applied structural diffusion tensor imaging (DTI to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS. GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA with basal ganglia (pre-SMA–putamen, SMA–putamen and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity.

  8. Lung fibroblasts share mesenchymal stem cell features which are altered in chronic obstructive pulmonary disease via the overactivation of the Hedgehog signaling pathway.

    Science.gov (United States)

    Figeac, Florence; Dagouassat, Maylis; Mahrouf-Yorgov, Meriem; Le Gouvello, Sabine; Trébeau, Céline; Sayed, Angeliqua; Stern, Jean-Baptiste; Validire, Pierre; Dubois-Randé, Jean-Luc; Boczkowski, Jorge; Mus-Veteau, Isabelle; Rodriguez, Anne-Marie

    2015-01-01

    Alteration of functional regenerative properties of parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they are impaired in COPD remain poorly understood. Apart from the role of fibroblasts in producing extracellular matrix, recent studies in organs different from the lung suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain that the Hedgehog pathway is altered in COPD patients thus aggravating the disease. Nevertheless, whether this pathway is dysregulated in COPD fibroblasts remains unknown. We investigated the stem cell features and the expression of Hedgehog components in human lung fibroblasts isolated from histologically-normal parenchymal tissue from 25 patients--8 non-smokers/non-COPD, 8 smokers-non COPD and 9 smokers with COPD--who were undergoing surgery for lung tumor resection. We found that lung fibroblasts resemble mesenchymal stem cells in terms of cell surface marker expression, differentiation ability and immunosuppressive potential and that these properties were altered in lung fibroblasts from smokers and even more in COPD patients. Furthermore, we showed that some of these phenotypic changes can be explained by an over activation of the Hedgehog signaling in smoker and COPD fibroblasts. Our study reveals that lung fibroblasts possess mesenchymal stem cell-features which are impaired in COPD via the contribution of an abnormal Hedgehog signaling. These processes should constitute a novel pathomechanism accounting for disease occurrence and progression.

  9. Adaptive mutations alter antibody structure and dynamics during affinity maturation.

    Science.gov (United States)

    Adhikary, Ramkrishna; Yu, Wayne; Oda, Masayuki; Walker, Ross C; Chen, Tingjian; Stanfield, Robyn L; Wilson, Ian A; Zimmermann, Jörg; Romesberg, Floyd E

    2015-03-24

    While adaptive mutations can bestow new functions on proteins via the introduction or optimization of reactive centers, or other structural changes, a role for the optimization of protein dynamics also seems likely but has been more difficult to evaluate. Antibody (Ab) affinity maturation is an example of adaptive evolution wherein the adaptive mutations may be identified and Abs may be raised to specific targets that facilitate the characterization of protein dynamics. Here, we report the characterization of three affinity matured Abs that evolved from a common germline precursor to bind the chromophoric antigen (Ag), 8-methoxypyrene-1,3,6-trisulfonate (MPTS). In addition to characterizing the sequence, molecular recognition, and structure of each Ab, we characterized the dynamics of each complex by determining their mechanical response to an applied force via three-pulse photon echo peak shift (3PEPS) spectroscopy and deconvoluting the response into elastic, anelastic, and plastic components. We find that for one Ab, affinity maturation was accomplished via the introduction of a single functional group that mediates a direct contact with MPTS and results in a complex with little anelasticity or plasticity. In the other two cases, more mutations were introduced but none directly contact MPTS, and while their effects on structure are subtle, their effects on anelasticity and plasticity are significant, with the level of plasticity correlated with specificity, suggesting that the optimization of protein dynamics may have contributed to affinity maturation. A similar optimization of structure and dynamics may contribute to the evolution of other proteins.

  10. DIFFERENT TYPES OF INSPIRATORY MUSCLE TRAINING PROVIDES BETTERMENT IN ALTERED PULMONARY FUNCTIONS IN UPPER THORACIC SPINAL CORD INJURIES

    Directory of Open Access Journals (Sweden)

    Muruganandam Periyasamy

    2016-08-01

    Full Text Available Background: Respiratory problems are usual in upper thoracic spinal cord injuries when compared to Lower thoracic spinal cord injuries. Generally there are frequent respiratory complications in the individuals with spinal cord injuries. The complications of the respiratory system are severe and more prevalent source of morbidity and mortality after the spinal cord injury due to the inefficient breathing capacity including inspiratory and expiratory abilities. The present study represents the inspiratory muscle training especially in upper thoracic spinal cord injury patients to assess the improvement in the pulmonary functions. Methods: Twenty five patients with the age between 25 -40 years with the upper spinal cord injuries were selected in the present study in order to assess the efficacy of the training. Several types of exercises were practiced including diaphragmatic breathing exercises, incentive spirometry, active cycle of breathing technique and weight training. COPD Conditions, Chest wall deformities, Hypertensive patients, Cardio vascular problems were excluded in the study. Results: The results from the study showed that significant changes were found in the patients treated with all the above mentioned techniques. Axillary level, nipple level, Xiphisternum levels were analysed and the results found to be significant after the treatment. Incentive spirometry and peak flow meter observations were also found to be significant when compare to the pretreatment. Conclusion: The present study conclude that the combined effect of incentive spriometry, diaphragmatic breathing exercises, and active cycle of breathing technique is more effective in improving the pulmonary functions in upper thoracic spinal cord injuries than single method efficiency.

  11. Altered Left Ventricular Geometry and Torsional Mechanics in High Altitude-Induced Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study.

    Science.gov (United States)

    De Boeck, Bart W; Toma, Aurel; Kiencke, Stephanie; Dehnert, Christoph; Zügel, Stefanie; Siebenmann, Christoph; Auinger, Katja; Buser, Peter T; Maggiorini, Marco; Kaufmann, Beat A

    2018-03-01

    Changes in left ventricular (LV) torsion have been related to LV geometry in patients with concomitant long-standing myocardial disease or pulmonary hypertension (PH). We evaluated the effect of acute high altitude-induced isolated PH on LV geometry, volumes, systolic function, and torsional mechanics. Twenty-three volunteers were prospectively studied at low altitude and after the second (D3) and third night (D4) at high altitude (4,559 m). LV ejection fraction, multidirectional strains and torsion, LV volumes, sphericity, and eccentricity were derived by speckle-tracking on three-dimensional echocardiographic data sets. Pulmonary pressure was estimated from the transtricuspid pressure gradient (TRPG), LV preload from end-diastolic LV volume, and transmitral over mitral annular E velocity (E/e'). At high altitude, oxygen saturation decreased by 15%-20%, heart rate and cardiac index increased by 15%-20%, and TRPG increased from 21 ± 2 to 37 ± 9 mm Hg (P geometry and torsional mechanics. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  12. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

    Science.gov (United States)

    Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

    2018-03-01

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

  13. The influence of temperature, phylogeny, and lung structure on the lipid composition of reptilian pulmonary surfactant.

    Science.gov (United States)

    Daniels, C B; Orgeig, S; Smits, A W; Miller, J D

    1996-01-01

    The lungs of all air-breathing vertebrates contain a form of pulmonary surfactant that lines the alveolar air-water interface where it modifies the interfacial surface tension. These pulmonary surfactants all consist of varying amounts of phospholipids (saturated and unsaturated) and cholesterol. The extent of variation between vertebrate groups and between species within a vertebrate group has been attributed to differences in factors such as phylogeny, body temperature, habitat, and lung structure. The influence of these factors on amphibian surfactant composition and function has been studied, but the reptiles, which comprise a polyphyletic group of vertebrates, have never been critically examined. The surfactant lipid composition from species belonging to the three groups of reptiles, the Archosauria (crocodiles), Lepidosauria (snakes and lizards), and Anapsida (turtles), has been determined. New data is presented in conjunction with already published data to create an evolutionary framework that concentrates particularly on the influence of phylogeny, body temperature, and lung structure on the composition of the surfactant lipids. Large amounts of pulmonary surfactant were found in all species of reptiles. All species lavaged at 23 degrees C (except C. atrox) demonstrated DSP/PL ratios of 23-33%. Animals with multicameral lungs exhibited an elevated CHOL/DSP ratio compared with species with unicameral lungs. In all groups, phosphatidylcholine (PC) was the dominant (60-80%) phospholipid. Phosphatidylserine and phosphatidylinositol (PS/PI) and sphingomyelin (S) represented the other phospholipids, while phosphatidylglycerol (PG), lysophosphatidylcholine (LPC), and phosphatidylethanolamine (PE) were occasionally observed. In two species of lizards (C. nuchalis and P. vitticeps), the saturated fatty acid, palmitic acid (16:0), was the dominant tail group on the phospholipids. Oleic acid (18:1) was the dominant monounsaturated fatty acid, whereas polyunsaturates

  14. Do edaphic aspects alter vegetation structures in the Brazilian restinga?

    Directory of Open Access Journals (Sweden)

    Francisco Soares Santos-Filho

    2013-09-01

    Full Text Available The vegetation of the Brazilian restinga (coastal woodland presents a variety of species and different characteristics, encompassing fields, fruit groves and forests on quartzarenic neosols. We hypothesised that the structure of the restinga landscape along the coast of the state of Piauí is influenced by edaphic factors and presents a pattern similar to that of other northeastern restingas. We evaluated three restingas in Piauí, using the quarter method to determine their structure. Composite soil samples were collected to determine their chemical and physical properties. Edaphic variables were correlated with plant species by canonical correspondence analysis (CCA. Phytosociological data for all three areas indicated regenerating vegetation comprising several small individuals, 82.5% of which showed a diameter at ground level < 13 cm. We also observed considerable tillering. In two of the areas, there was a predominance of Fabaceae species, such as Caesalpinia pyramidalis and Copaifera martii. Although the structural characteristics of the restingas studied were similar to those of other northeastern restingas, the former showed lower Shannon diversity indices (2.18-2.44. The CCA indicated that species distribution was influenced by edaphic factors such as pH, aluminium content and amount of organic matter. The restingas studied were similar to others along the Brazilian coast.

  15. Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways.

    Science.gov (United States)

    Rowan-Carroll, Andrea; Halappanavar, Sabina; Williams, Andrew; Somers, Christophers M; Yauk, Carole L

    2013-05-01

    It is clear that particulate air pollution poses a serious risk to human health; however, the underlying mechanisms are not completely understood. We investigated pulmonary transcriptional responses in mice following in-situ exposure to ambient air in a heavily industrialized urban environment. Mature C57BL/CBA male mice were caged in sheds near two working steel mills and a major highway in Hamilton, Ontario, Canada in the spring/summer of 2004. Control mice were housed in the same environment, but received only high-efficiency particle filtered air (HEPA). Whole lung tissues were collected from mice exposed for 3, 10, or for 10 weeks followed by 6 weeks recovery in the laboratory (16 weeks). DNA microarrays were used to profile changes in pulmonary gene expression. Transcriptional profiling revealed changes in the expression of genes implicated in the lipid droplet synthesis (Plin I, Dgat2, Lpl, S3-12, and Agpat2), and antioxidant defense (Ucp1) pathways in mice breathing unfiltered air. We postulate that exposure to urban air, containing an abundance of particulate matter adsorbed with polycyclic aromatic hydrocarbons, triggers lipid droplet (holding depots for lipids and malformed/excess proteins tagged for degradation) synthesis in the lungs, which may act to sequester particulates. Increased lipid droplet synthesis could lead to endogenous/stressor-induced production of reactive oxygen species and activation of antioxidant mechanisms. Further investigation into the stimulation of lipid droplet synthesis in the lung in response to air pollution and the resulting health implications is warranted. Copyright © 2013 Wiley Periodicals, Inc.

  16. Asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS): structured literature review and physician insights.

    Science.gov (United States)

    Ding, B; Enstone, A

    2016-01-01

    To understand the key characteristics of Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS) and to identify evidence gaps relating to the identification, treatment and management of ACOS patients. A structured literature review and 1-hour telephone interviews with specialist respiratory physicians were conducted (n=10; China, France, Germany, Japan and the USA). All 10 physicians used the term ACOS in clinical practice. ACOS was not clearly defined in the literature. Prevalence of ACOS among adult patients with COPD or asthma ranged from 12-55%. ACOS patients had severe disease, with increased exacerbations and hospitalisations compared to some asthma and COPD patients. ACOS represented a clinical challenge due to a lack of evidence-based guidelines distinguishing between asthma, COPD and ACOS. Published data quantifying ACOS costs were limited. There is a need for consensus evidence-based guidance to facilitate earlier diagnosis and to optimise the management of ACOS patients.

  17. White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment.

    Science.gov (United States)

    Su, Tanja; Caan, Matthan W A; Wit, Ferdinand W N M; Schouten, Judith; Geurtsen, Gert J; Cole, James H; Sharp, David J; Vos, Frans M; Prins, Maria; Portegies, Peter; Reiss, Peter; Majoie, Charles B

    2016-01-01

    Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIV+ patients remains unknown, as well as its possible association with cognitive impairment. We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV+ patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. We compared 100 aviraemic HIV+ men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. HIV+ patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increased mean diffusion. These white matter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/μl, but not with HIV-associated cognitive deficits. Cerebral white matter structure alterations are found in middle-aged HIV+ men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits. .

  18. Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

    Science.gov (United States)

    Habgood, Anthony N; Tatler, Amanda L; Porte, Joanne; Wahl, Sharon M; Laurent, Geoffrey J; John, Alison E; Johnson, Simon R; Jenkins, Gisli

    2016-06-01

    Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi(-/-) mice following injury. Slpi(-/-), and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by pSmad2 immunohistochemistry. The active-MMP-9 to pro-MMP-9 ratio was significantly increased in Slpi(-/-) animals compared with wild-type animals, demonstrating enhanced metalloproteinase activity. Wild-type animals showed an increase in TGF-β activation following bleomycin, with a progressive and sustained increase in collagen type I, alpha 1 (Col1α1), III, alpha 1(Col3α1), IV, alpha 1(Col4α1) mRNA expression, and a significant increase in total lung collagen 28 days post bleomycin. In contrast Slpi(-/-) mice showed no significant increase of alveolar TGF-β activity following bleomycin, above their already elevated levels, although global TGF-β activity did increase. Slpi(-/-) mice had impaired collagen gene expression but animals demonstrated minimal reduction in lung fibrosis compared with wild-type animals. These data suggest that enhanced proteolysis does not further enhance TGF-β activation, and inhibits sustained Col1α1, Col3α1, and Col4α1 gene expression

  19. Compositional and structural characterization of monolayers and bilayers composed of native pulmonary surfactant from wild type mice

    DEFF Research Database (Denmark)

    Bernardino de la Serna, Jorge; Hansen, Soren; Berzina, Zane

    2013-01-01

    This work comprises a structural and dynamical study of monolayers and bilayers composed of native pulmonary surfactant from mice. Spatially resolved information was obtained using fluorescence (confocal, wide field and two photon excitation) and atomic force microscopy methods. Lipid mass...... spectrometry experiments were also performed in order to obtain relevant information on the lipid composition of this material. Bilayers composed of mice pulmonary surfactant showed coexistence of distinct domains at room temperature, with morphologies and lateral packing resembling the coexistence of liquid...... between mono- and bi-layers composed of mice pulmonary surfactant were observed when the monolayers reach a surface pressure of 30 mN/m. This value is in line with theoretically predicted and recently measured surface pressures, where the monolayer-bilayer equivalence occurs in samples composed of single...

  20. Heterogeneous structure and surface tension effects on mechanical response in pulmonary acinus: A finite element analysis.

    Science.gov (United States)

    Koshiyama, Kenichiro; Nishimoto, Keisuke; Ii, Satoshi; Sera, Toshihiro; Wada, Shigeo

    2018-01-20

    The pulmonary acinus is a dead-end microstructure that consists of ducts and alveoli. High-resolution micro-CT imaging has recently provided detailed anatomical information of a complete in vivo acinus, but relating its mechanical response with its detailed acinar structure remains challenging. This study aimed to investigate the mechanical response of acinar tissue in a whole acinus for static inflation using computational approaches. We performed finite element analysis of a whole acinus for static inflation. The acinar structure model was generated based on micro-CT images of an intact acinus. A continuum mechanics model of the lung parenchyma was used for acinar tissue material model, and surface tension effects were explicitly included. An anisotropic mechanical field analysis based on a stretch tensor was combined with a curvature-based local structure analysis. The airspace of the acinus exhibited nonspherical deformation as a result of the anisotropic deformation of acinar tissue. A strain hotspot occurred at the ridge-shaped region caused by a rod-like deformation of acinar tissue on the ridge. The local structure becomes bowl-shaped for inflation and, without surface tension effects, the surface of the bowl-shaped region primarily experiences isotropic deformation. Surface tension effects suppressed the increase in airspace volume and inner surface area, while facilitating anisotropic deformation on the alveolar surface. In the lungs, the heterogeneous acinar structure and surface tension induce anisotropic deformation at the acinar and alveolar scales. Further research is needed on structural variation of acini, inter-acini connectivity, or dynamic behavior to understand multiscale lung mechanics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Bedfordshire County Structure Plan. Proposed alterations. Results of public consultation. Policy 97: Nuclear waste

    International Nuclear Information System (INIS)

    1984-01-01

    The document refers to Alterations to the County Structure Plan, proposed by Bedfordshire County Council and submitted to the Secretary of State for the Environment. An additional Alteration initiated at the County Council's meeting, dealing with nuclear waste, had not been the subject of prior public consultation. Consultation had since been arranged, and the present document summarises the responses that have been received, and describes the next action to be taken. (U.K.)

  2. Bedfordshire County Structure Plan. Proposed alterations -Public participation statement. Policy 97: Nuclear waste

    International Nuclear Information System (INIS)

    1984-01-01

    The document describes steps taken, in accord with the Town and Country Planning Act 1971, by Bedfordshire County Council, submitting proposed Alterations to the County Structure Plan to the Secretary of State for the Environment. When approving the submission the Council decided to add an additional Alteration dealing with nuclear waste: as this had not been the subject of public consultation the Council decided to seek the public's views on the proposal before submitting the Alteration. The arrangements for consultation and a list of persons and organizations consulted are given, together with the arrangements for considering comments. (U.K.)

  3. Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia

    NARCIS (Netherlands)

    H. IJsselstijn (Hanneke); N. Hung; J.C. de Jongste (Johan); D. Tibboel (Dick); E. Cutz

    1998-01-01

    textabstractCongenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We

  4. Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

    Directory of Open Access Journals (Sweden)

    Q Joyce Han

    Full Text Available Right ventricular (RV function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH. The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI to derive RV kinetic energy (KE work density and energy loss in the pulmonary artery (PA to better characterize RV work in PAH patients.4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA.PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007 as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001 throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction.This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

  5. 4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot

    Science.gov (United States)

    2012-01-01

    Background To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR). Methods CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test. Results 4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant. Conclusions Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics. PMID:22313680

  6. Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

    Science.gov (United States)

    Han, Q Joyce; Witschey, Walter R T; Fang-Yen, Christopher M; Arkles, Jeffrey S; Barker, Alex J; Forfia, Paul R; Han, Yuchi

    2015-01-01

    Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients. 4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA. PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction. This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

  7. On the pulmonary toxicity of oxygen. 5. Electronic structure and the paramagnetic property of oxygen.

    Science.gov (United States)

    Shanklin, D Radford

    2012-12-01

    only oxygen is paramagnetic. Magnetic effects on lesion formation were tested: [1] with ventilatory distress induced in newborn rabbits, and [2] in young adult female white mice exposed to 100% oxygen without added mechanical distress. A noninvasive model for ventilatory distress, thoracic restraint (TR), with longer mean survivals of 40-50hours, was employed rather than the Farber model. Parallel runs with TR, one subset receiving 100% oxygen in a plastic chamber resting on six strong ring magnets with measured fields up to +1200 gauss, the other plain 100% oxygen, were performed. Both subsets developed moderate metabolic acidosis with average weight losses circa 25%, but over different time courses, 82.89±4.91hours in magnetized oxygen, 55.4% longer than the 53.34±9.82hours in plain oxygen (p<0.001). The longer survival in magnetized oxygen meant extensive lung injury (99.57±0.42% pleural surface, versus 83.86±14.03%), but the rate of lesion formation was 30.89% faster in plain oxygen (1.5722% per hour) than in magnetized oxygen (1.2012% per hour), a difference significant at p<0.001. The effect of oxygen without mechanical ventilatory distress was examined in female adult white mice exposed to oxygen or magnetized oxygen. Similar survivals and weight losses were achieved. The rate of lung lesion formation was different, 1.2617% per hour in plain oxygen, 46.13% faster than 0.8634% per hour in magnetized oxygen. A variable magnetic field, with animals moving and breathing in chambers flooded with oxygen, has both systemic and pulmonary effects which alter the rate of lesion formation due to oxygen toxicity. Paramagnetic oxygen in a magnetic field influences the effect of oxygen toxicity on the lung but at these strengths of field it does not overcome significant mechanical disturbance. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Interstitial pulmonary alterations in visceral leishmaniasis: evaluation with high-resolution computed tomography; Alteracoes pulmonares intersticiais na leishmaniose visceral: avaliacao pela tomografia computadorizada de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Norma Selma Santos; Cerri, Giovanni Guido [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Dept. de Radiologia

    1999-08-01

    Visceral leishmaniasis, also called kala-azar, is a disease caused by a protozoan, the Leishmania donovani chagasi, that comprises reticuloendothelial system with involvement of the liver, spleen and bone marrow. It is endemic in some areas of northeastern Brazil and other countries of Latin America and Africa. The pathogenesis is related to the immunologic system of patients that present with the inability to activate the phagocytosis of the macrophages. As occurs in the liver and kidneys, the lungs are also involved with interstitial abnormalities caused by Leishmania that are not dependent upon the presence of the parasite. The histopathologic changes described are the involvement of inter alveolar septal in three different phases, irregularly and diffusely throughout the whole pulmonary parenchyma. This work analyzed high-resolution computed tomography (HRCT) of the thorax in 17 patients with visceral leishmaniasis in order to detect and characterize the abnormalities described in the anatomo pathologic findings reported in the literature. The HRCT is being used to evaluate chronic interstitial lung disease in a good correlation with histologic findings. The most common findings detected by HRCT were the reticular opacities that include peribronchovascular interstitial thickening and interlobular septal thickening an ground-glass opacity. The HRCT suggests that similar changes to that found in alveolar structures may occur in the secondary pulmonary lobule and that the involvement in the parenchymal interstitium represents the findings reported by pathological studies in visceral leishmaniasis. (author)

  9. Asexual Endophytes and Associated Alkaloids Alter Arthropod Community Structure and Increase Herbivore Abundances on a Native Grass

    Science.gov (United States)

    Dispite their minute biomass, microbial symbionts of plants potentially alter herbivory, diversity and community structure. Infection of grasses by asexual endophytic fungi often decreases herbivore loads and alters arthropod diverisy. However, most studies to date have involved agronomic grasses ...

  10. Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder.

    Science.gov (United States)

    Krause-Utz, Annegret; Frost, Rachel; Winter, Dorina; Elzinga, Bernet M

    2017-01-01

    Dissociation involves disruptions of usually integrated functions of consciousness, perception, memory, identity, and affect (e.g., depersonalization, derealization, numbing, amnesia, and analgesia). While the precise neurobiological underpinnings of dissociation remain elusive, neuroimaging studies in disorders, characterized by high dissociation (e.g., depersonalization/derealization disorder (DDD), dissociative identity disorder (DID), dissociative subtype of posttraumatic stress disorder (D-PTSD)), have provided valuable insight into brain alterations possibly underlying dissociation. Neuroimaging studies in borderline personality disorder (BPD), investigating links between altered brain function/structure and dissociation, are still relatively rare. In this article, we provide an overview of neurobiological models of dissociation, primarily based on research in DDD, DID, and D-PTSD. Based on this background, we review recent neuroimaging studies on associations between dissociation and altered brain function and structure in BPD. These studies are discussed in the context of earlier findings regarding methodological differences and limitations and concerning possible implications for future research and the clinical setting.

  11. Pulmonary aspergilloma

    Science.gov (United States)

    ... the aspergillus fungus is found. Alternative Names Fungus ball; Mycetoma; Aspergilloma; Aspergillosis - pulmonary aspergilloma Images Lungs Pulmonary nodule - front view chest x-ray Pulmonary nodule, solitary - CT ...

  12. Cold-induced alteration in the global structure of the male sex ...

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, dosage compensation occurs through hypertranscription of sex-linked genes in males. ... [Kulkarni-Shukla S., Barge A. P., Vartak R. S. and Kar A. 2008 Cold-induced alteration in the global structure of the male sex chromosome ..... forms acetylated at specific lysine residues define individual.

  13. Expression and structural-functional alterations of α-1-acid glycoprotein at the pathological state

    Directory of Open Access Journals (Sweden)

    Kulinich A. O.

    2010-07-01

    Full Text Available The review analyzes up-to-date knowledge on structure and biological functions of α-acid glycoprotein. The special attention is given to alterations of fucosylation, sialylation and branching of orosomucoid at the acute, chronic inflammation and oncotransformations.

  14. White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment

    NARCIS (Netherlands)

    Su, Tanja; Caan, Matthan W. A.; Wit, Ferdinand W. N. M.; Schouten, Judith; Geurtsen, Gert J.; Cole, James H.; Sharp, David J.; Vos, Frans M.; Prins, Maria; Portegies, Peter; Reiss, Peter; Majoie, Charles B.

    2016-01-01

    Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in

  15. Pulmonary venous remodeling in COPD-pulmonary hypertension and idiopathic pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Andersen, Kasper Hasseriis; Andersen, Claus Bøgelund; Gustafsson, Finn

    2017-01-01

    Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive...

  16. Experimental alteration of artificial and natural impact melt rock from the Chesapeake Bay impact structure

    Science.gov (United States)

    Declercq, J.; Dypvik, H.; Aagaard, Per; Jahren, J.; Ferrell, R.E.; Horton, J. Wright

    2009-01-01

    The alteration or transformation of impact melt rock to clay minerals, particularly smectite, has been recognized in several impact structures (e.g., Ries, Chicxulub, Mj??lnir). We studied the experimental alteration of two natural impact melt rocks from suevite clasts that were recovered from drill cores into the Chesapeake Bay impact structure and two synthetic glasses. These experiments were conducted at hydrothermal temperature (265 ??C) in order to reproduce conditions found in meltbearing deposits in the first thousand years after deposition. The experimental results were compared to geochemical modeling (PHREEQC) of the same alteration and to original mineral assemblages in the natural melt rock samples. In the alteration experiments, clay minerals formed on the surfaces of the melt particles and as fine-grained suspended material. Authigenic expanding clay minerals (saponite and Ca-smectite) and vermiculite/chlorite (clinochlore) were identified in addition to analcime. Ferripyrophyllite was formed in three of four experiments. Comparable minerals were predicted in the PHREEQC modeling. A comparison between the phases formed in our experiments and those in the cores suggests that the natural alteration occurred under hydrothermal conditions similar to those reproduced in the experiment. ?? 2009 The Geological Society of America.

  17. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

    Science.gov (United States)

    Chen, Kun; Hoffman, Eric A; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2016-12-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the "normal" subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

  18. Exercise-induced dehydration alters pulmonary function but does not modify airway responsiveness to dry air in athletes with mild asthma.

    Science.gov (United States)

    Simpson, A J; Romer, L M; Kippelen, P

    2017-05-01

    Local airway water loss is the main physiological trigger for exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effects of whole body water loss on airway responsiveness and pulmonary function in athletes with mild asthma and/or EIB. Ten recreational athletes with a medical diagnosis of mild asthma and/or EIB completed a randomized, crossover study. Pulmonary function tests, including spirometry, whole body plethysmography, and diffusing capacity of the lung for carbon monoxide (Dl CO ), were conducted before and after three conditions: 1 ) 2 h of exercise in the heat with no fluid intake (dehydration), 2 ) 2 h of exercise with ad libitum fluid intake (control), and 3 ) a time-matched rest period (rest). Airway responsiveness was assessed 2 h postexercise/rest via eucapnic voluntary hyperpnea (EVH) to dry air. Exercise in the heat with no fluid intake induced a state of mild dehydration, with a body mass loss of 2.3 ± 0.8% (SD). After EVH, airway narrowing was not different between conditions: median (interquartile range) maximum fall in forced expiratory volume in 1 s was 13 (7-15)%, 11 (9-24)%, and 12 (7-20)% in dehydration, control, and rest conditions, respectively. Dehydration caused a significant reduction in forced vital capacity (300 ± 190 ml, P = 0.001) and concomitant increases in residual volume (260 ± 180 ml, P = 0.001) and functional residual capacity (260 ± 250 ml, P = 0.011), with no change in Dl CO Mild exercise-induced dehydration does not exaggerate airway responsiveness to dry air in athletes with mild asthma/EIB but may affect small airway function. NEW & NOTEWORTHY This study is the first to investigate the effect of whole body dehydration on airway responsiveness. Our data suggest that the airway response to dry air hyperpnea in athletes with mild asthma and/or exercise-induced bronchoconstriction is not exacerbated in a state of mild dehydration. On the basis of alterations in lung volumes, however, exercise

  19. Effects of rho-kinase inhibition on pulmonary hypertension, lung growth, and structure in neonatal rats chronically exposed to hypoxia.

    Science.gov (United States)

    Ziino, Adrian J A; Ivanovska, Julijana; Belcastro, Rosetta; Kantores, Crystal; Xu, Emily Z; Lau, Mandy; McNamara, Patrick J; Tanswell, A Keith; Jankov, Robert P

    2010-02-01

    Rho-kinase (ROCK) inhibitors prevent pulmonary hypertension (PHT) in adult rodents, but little is known about their effects on the neonatal lung. Our objective was to examine the effects of ROCK inhibition on chronic hypoxia (CH)-induced PHT and abnormal lung structure in the neonatal rat. Pups were exposed to air or CH from postnatal d 1-14 while receiving Y-27632 (5 or 10 mg x kg(-1) x d(-1)), fasudil (20 mg x kg(-1) x d(-1)), or saline intraperitoneally. Relative to air, CH-exposed pups had increased pulmonary vascular resistance, right ventricular hypertrophy, arterial medial wall thickening, and abnormal distal airway morphology characterized by septal thinning and decreased secondary septation. Treatment with 10 mg/kg Y-27632 or fasudil attenuated the structural and hemodynamic changes of PHT while having no effect on septal thinning or inhibited secondary septation. In addition, Y-27632 (10 mg/kg) and fasudil augmented CH-induced somatic growth restriction. Pulmonary arteries of CH-exposed pups had increased ROCK activity, up-regulated expression of PDGF-BB and increased smooth muscle DNA synthesis, all of which were attenuated by treatment with 10 mg/kg Y-27632. Systemically administered ROCK inhibitors prevented PHT in the CH-exposed neonatal rat but at the cost of inhibited somatic growth. Limiting effects on vascular remodeling likely resulted, in major part, from attenuated vascular PDGF-BB/beta-receptor signaling.

  20. Structural genomic alterations in primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Twa, David D W; Steidl, Christian

    2015-01-01

    Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive non-Hodgkin lymphoma that displays phenotypic and genotypic similarity to Hodgkin lymphoma and diffuse large B-cell lymphoma. Studies using genome-wide discovery tools have revealed specific, recurrent structural aberrations as critical somatic events in the pathogenesis of PMBCL. These structural alterations prominently include transcript and protein altering rearrangements and copy number variations of the programmed death ligands 1 (CD274) and 2 (PDCD1LG2), CIITA, JAK2 and REL. Importantly, evidence is emerging that these acquired structural genomic changes, in synergy with other somatic alterations, contribute to PMBCL pathogenesis by influencing tumor microenvironment interactions that favor malignant B-cell growth. The means by which these rearrangements arise are not well understood. However, analysis of breakpoint junctions at base-pair resolution provides preliminary insight into putative rearrangement mechanisms. As the field also anticipates predictive value and therapeutic targeting of structural changes involving programmed death ligands and JAK2, a review of therapies that will likely shape future lymphoma treatment is needed.

  1. Population Structure among Mycobacterium tuberculosis Isolates from Pulmonary Tuberculosis Patients in Colombia

    Science.gov (United States)

    Realpe, Teresa; Correa, Nidia; Rozo, Juan Carlos; Ferro, Beatriz Elena; Gomez, Verónica; Zapata, Elsa; Ribon, Wellman; Puerto, Gloria; Castro, Claudia; Nieto, Luisa María; Diaz, Maria Lilia; Rivera, Oriana; Couvin, David; Rastogi, Nalin; Arbelaez, Maria Patricia; Robledo, Jaime

    2014-01-01

    Background Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. Principal Findings A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). Conclusions This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this

  2. Packaging and structural phenotype of brome mosaic virus capsid protein with altered N-terminal β-hexamer structure

    International Nuclear Information System (INIS)

    Wispelaere, Melissanne de; Chaturvedi, Sonali; Wilkens, Stephan; Rao, A.L.N.

    2011-01-01

    The first 45 amino acid region of brome mosaic virus (BMV) capsid protein (CP) contains RNA binding and structural domains that are implicated in the assembly of infectious virions. One such important structural domain encompassing amino acids 28 QPVIV 32 , highly conserved between BMV and cowpea chlorotic mottle virus (CCMV), exhibits a β-hexamer structure. In this study we report that alteration of the β-hexamer structure by mutating 28 QPVIV 32 to 28 AAAAA 32 had no effect either on symptom phenotype, local and systemic movement in Chenopodium quinoa and RNA profile of in vivo assembled virions. However, sensitivity to RNase and assembly phenotypes distinguished virions assembled with CP subunits having β-hexamer from those of wild type. A comparison of 3-D models obtained by cryo electron microscopy revealed overall similar structural features for wild type and mutant virions, with small but significant differences near the 3-fold axes of symmetry.

  3. In Situ Polymorphic Alteration of Filler Structures for Biomimetic Mechanically Adaptive Elastomer Nanocomposites.

    Science.gov (United States)

    Natarajan, Tamil Selvan; Okamoto, Shigeru; Stöckelhuber, Klaus Werner; Wießner, Sven; Reuter, Uta; Fischer, Dieter; Ghosh, Anik Kumar; Heinrich, Gert; Das, Amit

    2018-04-30

    A mechanically adaptable elastomer composite is prepared with reversible soft-stiff properties that can be easily controlled. By the exploitation of different morphological structures of calcium sulfate, which acts as the active filler in a soft elastomer matrix, the magnitude of filler reinforcement can be reversibly altered, which will be reflected in changes of the final stiffness of the material. The higher stiffness, in other words, the higher modulus of the composites, is realized by the in situ development of fine nanostructured calcium sulfate dihydrate crystals, which are formed during exposure to water and, further, these highly reinforcing crystals can be transformed to a nonreinforcing hemihydrate mesocrystalline structure by simply heating the system in a controlled way. The Young's modulus of the developed material can be reversibly altered from ∼6 to ∼17 MPa, and the dynamic stiffness (storage modulus at room temperature and 10 Hz frequency) alters its value in the order of 1000%. As the transformation is related to the presence of water molecules in the crystallites, a hydrophilic elastomer matrix was selected, which is a blend of two hydrophilic polymers, namely, epichlorohydrin-ethylene oxide-allyl glycidyl ether terpolymer and a terpolymer of ethylene oxide-propylene oxide-allyl glycidyl ether. For the first time, this method also provides a route to regulate the morphology and structure of calcium sulfate nanocrystals in a confined ambient of cross-linked polymer chains.

  4. Impact of industrial structure and soil exposure on the regional variations in pulmonary nontuberculous mycobacterial disease prevalence.

    Science.gov (United States)

    Hamada, Satoshi; Ito, Yutaka; Hirai, Toyohiro; Murase, Kimihiko; Tsuji, Takahiro; Fujita, Kohei; Mio, Tadashi; Maekawa, Koichi; Fujii, Takashi; Ono, Shigeki; Nishimura, Takashi; Hayashi, Akihiko; Komori, Toshiaki; Fujita, Naohisa; Niimi, Akio; Ichiyama, Satoshi; Chin, Kazuo; Mishima, Michiaki

    2016-06-01

    The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease, including Mycobacterium avium complex (MAC), varies widely according to geographic region. However, the factors that influence regional variations in pNTM disease prevalence remain unknown. This study was undertaken to examine whether environmental or occupational factors or host traits could influence regional variations in pNTM disease prevalence. We collected laboratory data on pulmonary tuberculosis (pTB) and pNTM from two hospitals in the West Harima area of Japan and five hospitals in Kyoto City, Japan from 2012 to 2013. We estimated microbiological pNTM disease prevalence by multiplying all pTB cases in each area with the ratio of pNTM cases and pTB cases at the survey hospitals in each area. We administered a standardized questionnaire to 52 patients and 120 patients with pulmonary MAC (pMAC) disease at Ako City Hospital and Kyoto University Hospital, respectively. The estimated prevalence of microbiological pNTM disease in the West Harima area (85.4/100,000 population-years) was significantly higher than that observed in Kyoto City (23.6/100,000 population-years; pEnvironmental factors, both industrial structures associated with occupational dust and environmental soil exposure, could influence the regional variations in pNTM disease prevalence. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

  5. Structure and composition of altered riparian forests in an agricultural Amazonian landscape.

    Science.gov (United States)

    Nagy, R Chelsea; Porder, Stephen; Neill, Christopher; Brando, Paulo; Quintino, Raimundo Mota; do Nascimento, Sebastiâo Aviz

    2015-09-01

    Deforestation and fragmentation influence the microclimate, vegetation structure, and composition of remaining patches of tropical forest. In the southern Amazon, at the frontier of cropland expansion, forests are converted and fragmented in a pattern that leaves standing riparian forests whose dimensions are mandated by the Brazilian National Forest Code. These altered riparian forests share many characteristics of well-studied upland forest fragments, but differ because they remain connected to larger areas of forest downstream, and because they may experience wetter soil conditions because reduction of forest cover in the surrounding watershed raises groundwater levels and increases stream runoff. We compared forest regeneration, structure, composition, and diversity in four areas of intact riparian forest and four areas each of narrow, medium, and wide altered riparian forests that have been surrounded by agriculture since the early 1980s. We found that seedling abundance was reduced by as much as 64% and sapling abundance was reduced by as much as 67% in altered compared to intact riparian forests. The most pronounced differences between altered and intact forest occurred near forest edges and within the narrowest sections of altered riparian forests. Woody plant species composition differed and diversity was reduced in altered forests compared to intact riparian forests. However, despite being fragmented for several decades, large woody plant biomass and carbon storage, the number of live or dead large woody plants, mortality rates, and the size distribution of woody plants did not differ significantly between altered and intact riparian forests. Thus, even in these relatively narrow forests with high edge: area ratios, we saw no evidence of the increases in mortality and declines in biomass that have been found in other tropical forest fragment studies. However, because of the changes in both species community and reduced regeneration, it is unclear how long

  6. Altered modular organization of structural cortical networks in children with autism.

    Directory of Open Access Journals (Sweden)

    Feng Shi

    Full Text Available Autism is a complex developmental disability that characterized by deficits in social interaction, language skills, repetitive stereotyped behaviors and restricted interests. Although great heterogeneity exists, previous findings suggest that autism has atypical brain connectivity patterns and disrupted small-world network properties. However, the organizational alterations in the autistic brain network are still poorly understood. We explored possible organizational alterations of 49 autistic children and 51 typically developing controls, by investigating their brain network metrics that are constructed upon cortical thickness correlations. Three modules were identified in controls, including cortical regions associated with brain functions of executive strategic, spatial/auditory/visual, and self-reference/episodic memory. There are also three modules found in autistic children with similar patterns. Compared with controls, autism demonstrates significantly reduced gross network modularity, and a larger number of inter-module connections. However, the autistic brain network demonstrates increased intra- and inter-module connectivity in brain regions including middle frontal gyrus, inferior parietal gyrus, and cingulate, suggesting one underlying compensatory mechanism associated with brain functions of self-reference and episodic memory. Results also show that there is increased correlation strength between regions inside frontal lobe, as well as impaired correlation strength between frontotemporal and frontoparietal regions. This alteration of correlation strength may contribute to the organization alteration of network structures in autistic brains.

  7. Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9.

    Science.gov (United States)

    Hirano, Seiichi; Nishimasu, Hiroshi; Ishitani, Ryuichiro; Nureki, Osamu

    2016-03-17

    The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets bearing a PAM (protospacer adjacent motif) and complementarity to the guide RNA. A recent study showed that, whereas wild-type Streptococcus pyogenes Cas9 (SpCas9) recognizes the 5'-NGG-3' PAM, the engineered VQR, EQR, and VRER SpCas9 variants recognize the 5'-NGA-3', 5'-NGAG-3', and 5'-NGCG-3' PAMs, respectively, thus expanding the targetable sequences in Cas9-mediated genome editing applications. Here, we present the high-resolution crystal structures of the three SpCas9 variants in complexes with a single-guide RNA and its altered PAM-containing, partially double-stranded DNA targets. A structural comparison of the three SpCas9 variants with wild-type SpCas9 revealed that the multiple mutations synergistically induce an unexpected displacement in the phosphodiester backbone of the PAM duplex, thereby allowing the SpCas9 variants to directly recognize the altered PAM nucleotides. Our findings explain the altered PAM specificities of the SpCas9 variants and establish a framework for further rational engineering of CRISPR-Cas9. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pulmonary aspects of obesity in critical care.

    Science.gov (United States)

    Siela, Debra

    2009-09-01

    Critically ill obese patients have many challenging pulmonary problems. The first key is to understand pathophysiology in the pulmonary system related to obesity. Second, it is important to identify the altered physical assessments and diagnostics that occur because of the pulmonary pathophysiology of obesity. Lastly, one should be aware of medical and nursing intervention options that treat symptoms or pulmonary problems of obesity. This article summarizes pulmonary issues related to obesity in critical care.

  9. Alteration of pulmonary blood flow in tetralogy of Fallot; Pre- and postoperative study with macroaggregates of [sup 99m]Tc-labeled human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kazuhiro; Matsui, Michihiko; Kurosawa, Hiromi; Arai, Tatsuta (Jikei Univ., Tokyo (Japan). School of Medicine); Nakamura, Yuzuru

    1992-10-01

    The pulmonary blood distribution was examined in 17 patients with tetralogy of Fallot (TOF) pre and postoperatively with macroaggregates of [sup 99m]TC-labeled human serum albumin. Most of the patients with TOF demonstrated an abnormal preoperative distribution pattern. The abnormalities included not only an unbalanced distribution between the right and left lungs but also a maldistribution of peripheral vessels in each lung. The right/left lung counts ratio and pulmonary peripheral index (calculated in order to express the severity of peripheral maldistribution) correlated neither to the diameter nor the cross-sectional area of either right or left pulmonary arteries which were measured angiographically. Postoperatively, the pulmonary blood was shunted toward the developed side of the lung which further contributed to maldistribution of blood flow and unbalanced pulmonary growth. Since the patients with an unbalanced pulmonary blood distribution demonstrated a higher right ventricular pressure one year after the operation, a palliative operation facilitating the growth of the underdeveloped side of the lung might be considered as an effective procedure to precede intracardiac repair. (author).

  10. Kinetics of radiation-induced structural alterations in electron-irradiated polymer-based composites

    International Nuclear Information System (INIS)

    Zaikin, Yu.A.; Potanin, A.S.; Koztaeva, U.P.

    2002-01-01

    Complete text of publication follows. In our previous studies measurements of internal friction temperature dependence were used for characterization of thermally activated and radiation-induced structural evolution in different types of polymer-based composites. This paper supplements these measurements with kinetic studies of internal friction (IF) parameters and EPR signals in a glass-cloth epoxy-filled laminate ST-ETF after electron irradiation up to doses of 1-10 MGy. Experiment have shown that the lifetime of free radicals in this composite considerably exceeds the characteristic time of molecular structural rearrangement due to scission and cross-linking after irradiation, as determined from IF measurements. This result is explained by slow proceeding of sterically hindered disproportionation reactions that stabilize the end groups of the macro-chain disrupt during irradiation and finally fix the act of scission. A mathematical model is formulated for description of structural evolution and alterations of IF parameters in polymer-based composites during and after electron irradiation. The description is based on the track model of radiation damage in polymers and phenomenological theory of radiation-induced structural transformations. General description does not give details of radiation-chemical conversion in different structural components of composites but indicates the direction of their structural evolution. In the model considered a composite material was divided into three parts (binder, filler, and a boundary layer). It was supposed that after primary distribution of radiation energy radiation-chemical conversion proceeds independently in each of these regions. It was also suggested that all the radical reactions were of the second order. On the example of glass-cloth laminate ST-ETF it is shown that this model allows to describe alterations in composite structural characteristics during irradiation and in the course of their self-organization after

  11. Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Yu Pan

    2017-01-01

    Full Text Available Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury (SCI. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 ± 14.10 years old; male:female, 7:11 and 18 healthy subjects (37.33 ± 11.79 years old; male:female, 7:11 were studied by resting state functional magnetic resonance imaging. Gray matter volume (GMV and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex (BA1 and left primary motor cortex (BA4, and left BA1 and left somatosensory association cortex (BA5 was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI

  12. Alterações histopatológicas pulmonares em pacientes com insuficiência respiratória aguda: um estudo em autopsias Pulmonary histopathological alterations in patients with acute respiratory failure: an autopsy study

    Directory of Open Access Journals (Sweden)

    Alexandre de Matos Soeiro

    2008-02-01

    Full Text Available OBJETIVOS: Apresentar alterações histopatológicas pulmonares encontradas em autopsias de pacientes falecidos por insuficiência respiratória aguda (IRA e verificar se doenças de base e específicos fatores de risco associados aumentam a incidência dessas alterações. MÉTODOS: Foram revisados laudos finais de autopsias e selecionadas 3.030 autopsias de pacientes > 1 ano de idade, com infiltrado pulmonar radiológico, portadores de doença de base e fatores de risco associados, que morreram por alterações pulmonares decorrentes de IRA. RESULTADOS: As principais alterações histopatológicas pulmonares causadoras de morte imediata foram: dano alveolar difuso (DAD; edema pulmonar; pneumonia intersticial linfocítica (PIL e hemorragia alveolar. As principais doenças de base encontradas foram: AIDS; broncopneumonia; sepse; cirrose hepática; tromboembolismo pulmonar; infarto agudo do miocárdio (IAM; acidente vascular cerebral; tuberculose; câncer; insuficiência renal crônica e leucemia. Os principais fatores de risco associados foram: idade > 50 anos; hipertensão arterial; insuficiência cardíaca congestiva; doença pulmonar obstrutiva crônica e diabetes mellitus. Pacientes com esses fatores de risco e AIDS apresentaram alta probabilidade de desenvolver PIL; pacientes com esses mesmos fatores, de desenvolver DAD, se portadores de sepse ou cirrose hepática; pacientes com tromboembolismo e os mesmos fatores de risco, de desenvolver hemorragia alveolar; pacientes com esses fatores de risco e IAM, de desenvolver edema pulmonar. CONCLUSÕES: Os achados pulmonares em pacientes com óbito por IRA apresentaram quatro padrões histopatológicos: DAD, edema pulmonar, PIL e hemorragia alveolar. Doenças de base e específicos fatores de risco associados correlacionaram-se positivamente com determinados padrões histopatológicos detectados à autópsia.OBJECTIVE: To present the pulmonary histopathological alterations found in the autopsies of

  13. Globally altered structural brain network topology in grapheme-color synesthesia.

    Science.gov (United States)

    Hänggi, Jürgen; Wotruba, Diana; Jäncke, Lutz

    2011-04-13

    Synesthesia is a perceptual phenomenon in which stimuli in one particular modality elicit a sensation within the same or another sensory modality (e.g., specific graphemes evoke the perception of particular colors). Grapheme-color synesthesia (GCS) has been proposed to arise from abnormal local cross-activation between grapheme and color areas because of their hyperconnectivity. Recently published studies did not confirm such a hyperconnectivity, although morphometric alterations were found in occipitotemporal, parietal, and frontal regions of synesthetes. We used magnetic resonance imaging surface-based morphometry and graph-theoretical network analyses to investigate the topology of structural brain networks in 24 synesthetes and 24 nonsynesthetes. Connectivity matrices were derived from region-wise cortical thickness correlations of 2366 different cortical parcellations across the whole cortex and from 154 more common brain divisions as well. Compared with nonsynesthetes, synesthetes revealed a globally altered structural network topology as reflected by reduced small-worldness, increased clustering, increased degree, and decreased betweenness centrality. Connectivity of the fusiform gyrus (FuG) and intraparietal sulcus (IPS) was changed as well. Hierarchical modularity analysis revealed increased intramodular and intermodular connectivity of the IPS in GCS. However, connectivity differences in the FuG and IPS showed a low specificity because of global changes. We provide first evidence that GCS is rooted in a reduced small-world network organization that is driven by increased clustering suggesting global hyperconnectivity within the synesthetes' brain. Connectivity alterations were widespread and not restricted to the FuG and IPS. Therefore, synesthetic experience might be only one phenotypic manifestation of the globally altered network architecture in GCS.

  14. Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant, N-acetyl-l-cysteine, and novel thiol antioxidant, N,N′-bis-2-mercaptoethyl isophthalamide

    Science.gov (United States)

    Patel, Rishi B.; Kotha, Sainath R.; Sauers, Lynn A.; Malireddy, Smitha; Gurney, Travis O.; Gupta, Niladri N.; Elton, Terry S.; Magalang, Ulysses J.; Marsh, Clay B.; Haley, Boyd E.; Parinandi, Narasimham L.

    2012-01-01

    Lung vascular alterations and pulmonary hypertension associated with oxidative stress have been reported to be involved in idiopathic lung fibrosis (ILF). Therefore, here, we hypothesize that the widely used lung fibrosis inducer, bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the monolayers of primary bovine pulmonary artery ECs to bleomycin (10 µg) and studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in the absence and presence of two thiol-redox protectants, the classic water-soluble N-acetyl-l-cysteine (NAC) and the novel hydrophobic N,N′-bis-2-mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of cells and filipodia formation), and cytoskeletal rearrangement (actin stress fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in a dose-dependent fashion. Furthermore, our study demonstrated the formation of reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier dysfunction (decrease of transendothelial electrical resistance), and enhanced paracellular transport (leak) of macromolecules. The observed bleomycin-induced EC alterations were attenuated by both NAC and NBMI, revealing that the novel hydrophobic thiol-protectant, NBMI, was more effective at µM concentrations as compared to the water-soluble NAC that was effective at mM concentrations in offering protection against the bleomycin-induced EC alterations. Overall, the results of the current study suggested the central role of thiol-redox in vascular EC dysfunction associated with ILF. PMID:22409285

  15. Structural health monitoring (vibration) as a tool for identifying structural alterations of the lumbar spine

    DEFF Research Database (Denmark)

    Kawchuk, Gregory N; Hartvigsen, Jan; Edgecombe, Tiffany

    2016-01-01

    Structural health monitoring (SHM) is an engineering technique used to identify mechanical abnormalities not readily apparent through other means. Recently, SHM has been adapted for use in biological systems, but its invasive nature limits its clinical application. As such, the purpose...

  16. A Viral RNA Structural Element Alters Host Recognition of Nonself RNA

    Energy Technology Data Exchange (ETDEWEB)

    Hyde, J. L.; Gardner, C. L.; Kimura, T.; White, J. P.; Liu, G.; Trobaugh, D. W.; Huang, C.; Tonelli, M.; Paessler, S.; Takeda, K.; Klimstra, W. B.; Amarasinghe, G. K.; Diamond, M. S.

    2014-01-30

    Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.

  17. Polycyclic aromatic hydrocarbons alter the structure of oceanic and oligotrophic microbial food webs

    KAUST Repository

    Cerezo, Maria Isabel

    2015-11-01

    One way organic pollutants reach remote oceanic regions is by atmospheric transport. During the Malaspina-2010 expedition, across the Atlantic, Indian, and Pacific Oceans, we analyzed the polycyclic aromatic hydrocarbon (PAH) effects on oceanic microbial food webs. We performed perturbation experiments adding PAHs to classic dilution experiments. The phytoplankton growth rates were reduced by more than 5 times, being Prochlorococcus spp. the most affected. 62% of the experiments showed a reduction in the grazing rates due to the presence of PAHs. For the remaining experiments, grazing usually increased likely due to cascading effects. We identified changes in the slope of the relation between the growth rate and the dilution fraction induced by the pollutants, moving from no grazing to V-shape, or to negative slope, indicative of grazing increase by cascade effects and alterations of the grazers\\' activity structure. Our perturbation experiments indicate that PAHs could influence the structure oceanic food-webs structure.

  18. Pulmonary Rehabilitation

    Science.gov (United States)

    Pulmonary rehabilitation (rehab) is a medically supervised program to help people who have chronic breathing problems, including COPD (chronic obstructive pulmonary disease) Sarcoidosis Idiopathic pulmonary fibrosis Cystic fibrosis During ...

  19. Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure.

    Directory of Open Access Journals (Sweden)

    Marco Maccarana

    Full Text Available The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs. Not all SLRPs' effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry. Electron microscopy analyses showed 7% thinner collagen fibrils in Aspn-/- mice (not statistically significant. Several matrix genes were upregulated, including collagens (Col1a1, Col1a2, Col3a1, matrix metalloproteinases (Mmp2, Mmp3 and lysyl oxidases (Lox, Loxl2, while lysyl hydroxylase (Plod2 was downregulated. Intriguingly no differences were observed in collagen protein content or in collagen cross-linking-related lysine oxidation or hydroxylation. The glycosaminoglycan content and structure in Aspn-/- skin was profoundly altered: chondroitin/dermatan sulfate was more than doubled and had an altered composition, while heparan sulfate was halved and had a decreased sulfation. Also, decorin and biglycan were doubled in Aspn-/- skin. Overall, asporin deficiency changes skin glycosaminoglycan composition, and decorin and biglycan content, which may explain the changes in skin mechanical properties.

  20. Structural and functional alterations of catalase induced by acriflavine, a compound causing apoptosis and necrosis.

    Science.gov (United States)

    Attar, Farnoosh; Khavari-Nejad, Sarah; Keyhani, Jacqueline; Keyhani, Ezzatollah

    2009-08-01

    Acriflavine is an antiseptic agent causing both apoptosis and necrosis in yeast. In this work, its effect on the structure and function of catalase, a vital enzyme actively involved in protection against oxidative stress, was investigated. In vitro kinetic studies showed that acriflavine inhibited the enzymatic activity in a competitive manner. The residual activity detectable after preincubation of catalase (1.5 nmol/L) with various concentrations of acriflavine went from 50% to 20% of the control value as the acriflavine concentration increased from 30 to 90 micromol/L. Correlatively with the decrease in activity, alterations in the enzyme's conformation were observed as indicated by fluorescence spectroscopy, circular dichroism spectroscopy, and electronic absorption spectroscopy. The enzyme's intrinsic fluorescence obtained upon excitation at either 297 nm (tryptophan residues) or 280 nm (tyrosine and tryptophan residues) decreased as a function of acriflavine concentration. Circular dichroism studies showed alterations of the protein structure by acriflavine with up to 13% decrease in alpha helix, 16% increase in beta-sheet content, 17% increase in random coil, and 4% increase in beta turns. Spectrophotometric studies showed a blueshift and modifications in the chromicity of catalase at 405 nm, corresponding to an absorbance band due to the enzyme's prosthetic group. Thus, acriflavine induced in vitro a profound change in the structure of catalase so that the enzyme could no longer function. Our results showed that acriflavine, a compound producing apoptosis and necrosis, can have a direct effect on vital functions in cells by disabling key enzymes.

  1. [Metabolic syndrome and ageing: cognitive impairment and structural alterations of the central nervous system].

    Science.gov (United States)

    Segura, B; Jurado, M A

    The metabolic syndrome is a cluster of vascular risk factors, including: hypertension, insulin resistance, low levels of high density lipoproteins, high levels of triglycerides and obesity. Nowadays the prevalence of the syndrome in the developmental societies increases and it is related to aging. To review the relation of metabolic syndrome to the cognitive impairment and cerebrovascular alterations during the aging. The syndrome involves higher risk of vascular pathologies and recently has been related to the pathological aging, including cognitive impairment and structural damage in the central nervous system. Specifically the studies about metabolic syndrome have described a profile of higher general cognitive impairment and higher risk of dementia, as well as concrete neuropsychological deficits probably related to white matter alterations. The independent effects of vascular risk factors in cognition have been studied before as well as their influences in structural integrity of the brain. Nowadays further research is necessary to know if the metabolic syndrome effects on cognition and brain are greater than the sum of the effect of his components. In the future the knowledge about the cognitive and structural damage due to the syndrome could be useful to design prevention programs and promote the healthy aging.

  2. Structural Basis for the Altered PAM Recognition by Engineered CRISPR-Cpf1.

    Science.gov (United States)

    Nishimasu, Hiroshi; Yamano, Takashi; Gao, Linyi; Zhang, Feng; Ishitani, Ryuichiro; Nureki, Osamu

    2017-07-06

    The RNA-guided Cpf1 nuclease cleaves double-stranded DNA targets complementary to the CRISPR RNA (crRNA), and it has been harnessed for genome editing technologies. Recently, Acidaminococcus sp. BV3L6 (AsCpf1) was engineered to recognize altered DNA sequences as the protospacer adjacent motif (PAM), thereby expanding the target range of Cpf1-mediated genome editing. Whereas wild-type AsCpf1 recognizes the TTTV PAM, the RVR (S542R/K548V/N552R) and RR (S542R/K607R) variants can efficiently recognize the TATV and TYCV PAMs, respectively. However, their PAM recognition mechanisms remained unknown. Here we present the 2.0 Å resolution crystal structures of the RVR and RR variants bound to a crRNA and its target DNA. The structures revealed that the RVR and RR variants primarily recognize the PAM-complementary nucleotides via the substituted residues. Our high-resolution structures delineated the altered PAM recognition mechanisms of the AsCpf1 variants, providing a basis for the further engineering of CRISPR-Cpf1. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

    2017-01-01

    The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

  4. Functional and structural neural alterations in Internet gaming disorder: A systematic review and meta-analysis.

    Science.gov (United States)

    Yao, Yuan-Wei; Liu, Lu; Ma, Shan-Shan; Shi, Xin-Hui; Zhou, Nan; Zhang, Jin-Tao; Potenza, Marc N

    2017-12-01

    This meta-analytic study aimed to identify the common and specific neural alterations in Internet gaming disorder (IGD) across different domains and modalities. Two separate meta-analyses for functional neural activation and gray-matter volume were conducted. Sub-meta-analyses for the domains of reward, cold-executive, and hot-executive functions were also performed, respectively. IGD subjects, compared with healthy controls, showed: (1) hyperactivation in the anterior and posterior cingulate cortices, caudate, posterior inferior frontal gyrus (IFG), which were mainly associated with studies measuring reward and cold-executive functions; and, (2) hypoactivation in the anterior IFG in relation to hot-executive function, the posterior insula, somatomotor and somatosensory cortices in relation to reward function. Furthermore, IGD subjects showed reduced gray-matter volume in the anterior cingulate, orbitofrontal, dorsolateral prefrontal, and premotor cortices. These findings suggest that IGD is associated with both functional and structural neural alterations in fronto-striatal and fronto-cingulate regions. Moreover, multi-domain assessments capture different aspects of neural alterations in IGD, which may be helpful for developing effective interventions targeting specific functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Structural learning difficulties implicate altered hippocampal functioning in adults with autism spectrum disorder.

    Science.gov (United States)

    Ring, Melanie; Derwent, Claire L T; Gaigg, Sebastian B; Bowler, Dermot M

    2017-08-01

    Structural learning is fundamental to the formation of cognitive maps that are necessary for learning, memory, and spatial navigation. It also enables successful navigation of the social world, which is something that individuals with autism spectrum disorder (ASD) find particularly difficult. To master these situations, a person needs to bind pieces of information to one another and to consider the context in which experiences happen. Such binding is a capacity of the hippocampus. Although altered hippocampal function has for long been suspected to play a role in the etiology of ASD, the relevant evidence has remained inconclusive because few behavioral tests that are known to specifically necessitate preserved hippocampal function have been employed in studies of ASD. To address this gap in the literature, a total sample of 57 pairs of age and ability matched ASD and comparison participants was divided into 3 subsamples who were asked either to complete structural learning, or 1 of 2 configural learning control tasks (biconditional discrimination and transverse patterning) drawn from animal research. As predicted, ASD adults demonstrated specific difficulty with structural learning but not with other forms of configural learning. These differences were not attributable to decreased attentional shifting or increased perseveration, which would have indicated atypical frontal modulation of hippocampal processes. Instead, the observations implicate atypical hippocampal functioning as the source of structural learning difficulties in ASD. The data suggest that disturbances in domain-general cognitive processes such as structural learning, caused by altered hippocampal function, play a critical role in the etiology of ASD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Structural brain alterations in patients with lumbar disc herniation: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Michael Luchtmann

    Full Text Available Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the

  7. Pulmonary mitochondrial alterations and oxidative stress in response to ozone exposure: Effects of age and an omega-3 enriched diet; Alterations mitochondriales et stress oxydant pulmonaire en reponse a l'ozone: effets de l'age et d'une supplementation en omega-3

    Energy Technology Data Exchange (ETDEWEB)

    Servais, St.

    2004-04-15

    Ozone (O{sub 3}) is one of the molecular species most reactive to which are exposed living species. O{sub 3} acts primarily on the pulmonary system by inducing oxidative stress. Because susceptibility to oxidative stress varies with age, we studied alterations of pulmonary balance between production of reactive oxygen species (ROS) and their elimination, in immature (21 days), adult (6 months) and old rats (20 months) during O{sub 3} exposure (0,5 ppm, 12 h/day for 7 days). For this purpose we have specifically studied pulmonary mitochondria as ROS source, main antioxidant enzyme activities, contents in stress protein (HSP72), 8-oxodGuo and DNA adducts resulting from lipid peroxidation. These works have shown that our protocol of O{sub 3} exposure did not induce lung oxidative stress in adult rats. We confirmed that immature and old rats were more sensitive during O{sub 3} challenge than adults. Indeed, O{sub 3} generates oxidative stress which leads to modification of ventilatory function and pulmonary DNA oxidation in these two populations. Parameters which take part in greatest susceptibility to O{sub 3} differ according to the age. We concluded that the mitochondria is not a major source of pulmonary ROS in our model of O{sub 3} exposure. Secondly, with the sights of anti-inflammatory properties of polyunsaturated fatty acids {omega}3, we studied the effect of a {omega}3 supplementation in immature and old rats exposed to O{sub 3}. The supplementation in {omega}3 limits the pulmonary DNA oxidation in immature and old rats. Paradoxically, in old rats this supplementation provokes an increase in lipid peroxidation susceptibility. (author)

  8. Pulmonary and cardiac function in asymptomatic obese subjects and changes following a structured weight reduction program: a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Matthias Held

    Full Text Available BACKGROUND: The prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear. OBJECTIVE: To determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters. METHODS: We prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program. RESULTS: 74 subjects (32 male, 42 female; mean age 42±12 years with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = -0.42, p<0.001, FEV1 (R = -0.497, p<0.001 and positively with P 0.1 (R = 0.32, p = 0.02 and myocardial mass (R = 0.419, p = 0.002. After 4 months the study subjects had significantly reduced their body weight (-26.0±11.8 kg and BMI (-8.9±3.8 associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5% pred., p<0.001; FEV1+9.8±8.3% pred., p<0.001, ITGV+16.4±16.0% pred., p<0.001, SR tot -17.4±41.5% pred., p<0.01. Moreover, P0.1/Pimax decreased to 47.7% (p<0.01 indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = -0.31, p = 0.03. Echocardiography demonstrated reduced myocardial wall thickness (-0.08±0.2 cm, p = 0.02 and improved left ventricular myocardial performance index (-0.16±0.35, p = 0.02. Mitral annular plane systolic excursion (+0.14, p = 0.03 and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001 increased. CONCLUSION: Even in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the

  9. Myocardial Structural Alteration and Systolic Dysfunction in Preclinical Hypertrophic Cardiomyopathy Mutation Carriers

    Science.gov (United States)

    Yiu, Kai Hang; Atsma, Douwe E.; Delgado, Victoria; Ng, Arnold C. T.; Witkowski, Tomasz G.; Ewe, See Hooi; Auger, Dominique; Holman, Eduard R.; van Mil, Anneke M.; Breuning, Martijn H.; Tse, Hung Fat; Bax, Jeroen J.; Schalij, Martin J.; Marsan, Nina Ajmone

    2012-01-01

    Background To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. Methods and Findings Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen−) were observed. Twenty-five control subjects, matched with the Mut+/Phen− group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (−14.0±4.6 dB, p−19.0 dB basal anteroseptal cIBS or >−18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen− group from controls. Conclusion The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen− patients from controls with important clinical implications for the family screening and follow-up of these patients. PMID:22574137

  10. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-07-04

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  11. Structure and component alteration of rabbit Achilles tendon in tissue culture.

    Science.gov (United States)

    Hosaka, Yoshinao; Ueda, Hiromi; Yamasaki, Tadatsugu; Suzuki, Daisuke; Matsuda, Naoya; Takehana, Kazushige

    2005-12-01

    The aim of this study was to investigate alterations of cultured tendon tissues to determine whether tissue culture is a useful method for biological analyses of the tendon. Tendon tissues for tissue culture were isolated from Achilles tendons of rabbits. The tendon segments were placed one segment per well and incubated in growth medium consisting of Dullbecco's modified Eagle's medium supplemented with 5% fetal bovine serum at 37 degrees C in a humidified atmosphere with 5% CO(2) for various periods. The alignment of collagen fibrils was preserved for 48 h, but tendon structure has disintegrated at 96 h. Alcian blue staining and gelatine zymography revealed that proteoglycan markedly diminished and that matrix metalloproteinase (MMPs) activity was upregulated sharply at 72 and 96 h. The ratio of collagen fibrils with large diameter had increased and the mean diameter and mass average diameter value had reached maximum at 48 h. The values then decreased and mean diameters at 72 and 96 h were significantly different from that at 48 h. At 96 h, the ratio of collagen fibrils with small diameters had increased and collagen fibrils with large diameters had disappeared. These findings indicate that structural alteration is possible to be induced by disintegration of collagen fibrils and disappearance of glycosaminoglycans from extracellular matrix (ECM), subsequent of upregulation of MMPs activity. Although the study period is limited, the tissue culture method is available for investigating cell-ECM interaction in tendons.

  12. Structural brain alterations in primary open angle glaucoma: a 3T MRI study

    Science.gov (United States)

    Wang, Jieqiong; Li, Ting; Sabel, Bernhard A.; Chen, Zhiqiang; Wen, Hongwei; Li, Jianhong; Xie, Xiaobin; Yang, Diya; Chen, Weiwei; Wang, Ningli; Xian, Junfang; He, Huiguang

    2016-01-01

    Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma. PMID:26743811

  13. Quantitative analysis of nanoscale intranuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy imaging

    Science.gov (United States)

    Sahay, Peeyush; Shukla, Pradeep K.; Ghimire, Hemendra M.; Almabadi, Huda M.; Tripathi, Vibha; Mohanty, Samarendra K.; Rao, Radhakrishna; Pradhan, Prabhakar

    2017-04-01

    Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging. The results, which were obtained at length scales ranging from ~30 to 200 nm, show that 10-12 week-old mice fed a Lieber-DeCarli liquid (alcoholic) diet had a higher degree of structural alteration than control mice fed a normal diet without alcohol. The degree of structural alteration became significantly distinguishable at a sample length of ~100 nm, which is the typical length scale of the building blocks of cells, such as DNA, RNA, proteins and lipids. Interestingly, different degrees of structural alteration at such length scales suggest possible structural rearrangement of chromatin inside the nuclei in chronic alcoholism.

  14. High-fat diet enhances mammary tumorigenesis and pulmonary metastasis and alters inflammatory and angiogenic profiles in MMTV-PyMT mice

    Science.gov (United States)

    The MMTV-PyMT transgenic mouse model is commonly used to study luminal B breast cancer, which has a lower prevalence but a worse prognosis. The objective of the present study was to determine whether an obesogenic, high-fat diet enhances primary tumorigenesis and pulmonary metastasis in female MMTV...

  15. Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig

    Directory of Open Access Journals (Sweden)

    Martínez Anna

    2009-08-01

    Full Text Available Abstract Background Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages. The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs. Methods 19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods. Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP. The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of α-actin and desmin. Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically. The expression of endothelial nitric oxide synthase (eNOS was evaluated by Real Time-PCR. Results Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p Conclusion In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS. These changes appear after 3 months of exposure and precede the development of pulmonary emphysema.

  16. Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study.

    Science.gov (United States)

    Szkudlarek, A; Maciążek-Jurczyk, M; Chudzik, M; Równicka-Zubik, J; Sułkowska, A

    2016-01-15

    The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by (1)H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. A multivariate pattern analysis study of the HIV-related white matter anatomical structural connections alterations

    Science.gov (United States)

    Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie

    2017-03-01

    It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.

  18. Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ait Mou, Younss; Lacampagne, Alain; Irving, Thomas; Scheuermann, Valérie; Blot, Stéphane; Ghaleh, Bijan; de Tombe, Pieter P.; Cazorla, Olivier

    2018-01-01

    Aim Duchenne Muscular Dystrophy (DMD) is associated with progressive depressed left ventricular (LV) function. However, DMD effects on myofilament structure and function are poorly understood. Golden Retriever Muscular Dystrophy (GRMD) is a dog model of DMD recapitulating the human form of DMD. Objective The objective of this study is to evaluate myofilament structure and function alterations in GRMD model with spontaneous cardiac failure. Methods and results We have employed synchrotron X-rays diffraction to evaluate myofilament lattice spacing at various sarcomere lengths (SL) on permeabilized LV myocardium. We found a negative correlation between SL and lattice spacing in both sub-epicardium (EPI) and sub-endocardium (ENDO) LV layers in control dog hearts. In the ENDO of GRMD hearts this correlation is steeper due to higher lattice spacing at short SL (1.9 μm). Furthermore, cross-bridge cycling indexed by the kinetics of tension redevelopment (ktr) was faster in ENDO GRMD myofilaments at short SL. We measured post-translational modifications of key regulatory contractile proteins. S-glutathionylation of cardiac Myosin Binding Protein-C (cMyBP-C) was unchanged and PKA dependent phosphorylation of the cMyBP-C was significantly reduced in GRMD ENDO tissue and more modestly in EPI tissue. Conclusions We found a gradient of contractility in control dogs' myocardium that spreads across the LV wall, negatively correlated with myofilament lattice spacing. Chronic stress induced by dystrophin deficiency leads to heart failure that is tightly associated with regional structural changes indexed by increased myofilament lattice spacing, reduced phosphorylation of regulatory proteins and altered myofilament contractile properties in GRMD dogs.

  19. Preliminary study of visualizing membrane structures of spiculated pulmonary nodules in three-dimensional thoracic CT images

    Science.gov (United States)

    Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

    2016-03-01

    Research results from the National Lung Screening Trial revealed that screening for lung cancer with low-dose CT (LDCT) reduces lung cancer mortality in heavy smokers by 20% compared to radiography. While this study does show the efficacy of CT-based screening, radiologists often face the problem of estimating the malignant likelihoods of pulmonary nodules detected on LDCT screening for maximizing patient survival and for preserving lung function. Spiculation is considered as one of the indicators of nodule malignancy and an important feature to assess requirements on a patient-tailored follow-up procedure. However, the spiculation is also observed in some benign nodules, particularly in tuberculoma. The elucidation of the spliculation morphology in 3D thoracic CT images is an important preliminary step towards developing the malignant discrimination strategies from benign nodules. In this study, we present a visualization method to reveal a spatial configuration of spiculation of pulmonary nodules in three-dimensional thoracic CT images. Applying the method to an example of malignant nodule with the spiculated margins, the visualizing preliminary result of the spatial configuration reveals the presence of membrane structures of spiculation.

  20. Pulmonary hypertension CT imaging

    International Nuclear Information System (INIS)

    Nedevska, A.

    2013-01-01

    Full text: The right heart catheterization is the gold standard in the diagnosis and determines the severity of pulmonary hypertension. The significant technical progress of noninvasive diagnostic imaging methods significantly improves the pixel density and spatial resolution in the study of cardiovascular structures, thus changes their role and place in the overall diagnostic plan. Learning points: What is the etiology, clinical manifestation and general pathophysiological disorders in pulmonary hypertension. What are the established diagnostic methods in the diagnosis and follow-up of patients with pulmonary hypertension. What is the recommended protocol for CT scanning for patients with clinically suspected or documented pulmonary hypertension. What are the important diagnostic findings in CT scan of a patient with pulmonary hypertension. Discussion: The prospect of instantaneous complex - anatomical and functional cardiopulmonary and vascular diagnostics seems extremely attractive. The contrast enhanced multislice computed (CT ) and magnetic resonance imaging are very suitable methods for imaging the structures of the right heart, with the possibility of obtaining multiple projections and three-dimensional imaging reconstructions . There are specific morphological features that, if carefully analyzed, provide diagnostic information. Thus, it is possible to avoid or at least reduce the frequency of use of invasive diagnostic cardiac catheterization in patients with pulmonary hypertension. Conclusion: This review focuses on the use of contrast-enhanced CT for comprehensive evaluation of patients with pulmonary hypertension and presents the observed characteristic changes in the chest, lung parenchyma , the structures of the right half of the heart and pulmonary vessels

  1. Structural alterations of the superior temporal gyrus in schizophrenia: Detailed subregional differences.

    Science.gov (United States)

    Ohi, K; Matsuda, Y; Shimada, T; Yasuyama, T; Oshima, K; Sawai, K; Kihara, H; Nitta, Y; Okubo, H; Uehara, T; Kawasaki, Y

    2016-05-01

    Reduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus. We acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification. As expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics. These findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. alpha-Globin genes: thalassemic and structural alterations in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.R.S.C. Wenning

    2000-09-01

    Full Text Available Seven unrelated patients with hemoglobin (Hb H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, aaNcoI, alphaIcalpha and alphaTSaudialpha was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(aaT]. Among the 27 patients with structural alterations, 15 (of Italian descent had Hb Hasharon (alpha47Asp->His associated with the -alpha3.7 deletion, 4 (of Italian descent were heterozygous for Hb J-Rovigo (alpha53Ala->Asp, 4 (3 Blacks and 1 Caucasian were heterozygous for Hb Stanleyville-II (alpha78Asn->Lys associated with the alpha+-thalassemia, 1 (Black was heterozygous for Hb G-Pest (alpha74Asp->Asn, 1 (Caucasian was heterozygous for Hb Kurosaki (alpha7Lys->Glu, 1 (Caucasian was heterozygous for Hb Westmead (alpha122His->Gln, and 1 (Caucasian was the carrier of a novel silent variant (Hb Campinas, alpha26Ala->Val. Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.

  3. Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells.

    Science.gov (United States)

    Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L; Han, Jessica H; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H; Bussey, Kimberly J; Meldrum, Deirdre R

    2016-08-09

    The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an 'epigenetic' drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat's differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

  4. Experience-dependent plasticity in white matter microstructure: Reasoning training alters structural connectivity

    Directory of Open Access Journals (Sweden)

    Allyson P Mackey

    2012-08-01

    Full Text Available Diffusion tensor imaging (DTI techniques have made it possible to investigate white matter plasticity in humans. Changes in DTI measures, principally increases in fractional anisotropy (FA, have been observed following training programs as diverse as juggling, meditation, and working memory. Here, we sought to test whether three months of reasoning training could alter white matter microstructure. We recruited participants (n=23 who were enrolled in a course to prepare for the Law School Admission Test (LSAT, a test that places strong demands on reasoning skills, as well as age- and IQ-matched controls planning to take the LSAT in the future (n=22. DTI data were collected at two scan sessions scheduled three months apart. In trained participants but not controls, we observed decreases in radial diffusivity (RD in white matter connecting frontal cortices, and in mean diffusivity (MD within frontal and parietal lobe white matter. Further, participants exhibiting larger gains on the LSAT exhibited greater decreases in MD in the right internal capsule. In summary, reasoning training altered multiple measures of white matter structure in young adults. While the cellular underpinnings are unknown, these results provide evidence of experience-dependent white matter changes that may not be limited to myelination.

  5. Nitric oxide and oxidative stress is associated with severity of diabetic retinopathy and retinal structural alterations.

    Science.gov (United States)

    Sharma, Shashi; Saxena, Sandeep; Srivastav, Khushboo; Shukla, Rajendra K; Mishra, Nibha; Meyer, Carsten H; Kruzliak, Peter; Khanna, Vinay K

    2015-07-01

    The aim of the study was to determine plasma nitric oxide (NO) and lipid peroxide (LPO) levels in diabetic retinopathy and its association with severity of disease. Prospective observational study. A total of 60 consecutive cases and 20 healthy controls were included. Severity of retinopathy was graded according to early treatment diabetic retinopathy study (ETDRS) classification. Photoreceptor inner segment ellipsoid band (ISel) disruption and retinal pigment epithelium (RPE) alteration were graded using spectral domain optical coherence tomography. Data were statistically analyzed. Plasma thiobarbituric acid reactive substances, NO assay and reduced glutathione (GSH) were measured using standard protocol. Increased severity of diabetic retinopathy was significantly associated with increase in plasma levels of LPO (P diabetic retinopathy. For the first time, it has been demonstrated that increased plasma LPO, NO and decreased GSH levels are associated with in vivo structural changes in inner segment ellipsoid and RPE. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

  6. Altered topological organization of white matter structural networks in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Yaou Liu

    Full Text Available OBJECTIVE: To investigate the topological alterations of the whole-brain white-matter (WM structural networks in patients with neuromyelitis optica (NMO. METHODS: The present study involved 26 NMO patients and 26 age- and sex-matched healthy controls. WM structural connectivity in each participant was imaged with diffusion-weighted MRI and represented in terms of a connectivity matrix using deterministic tractography method. Graph theory-based analyses were then performed for the characterization of brain network properties. A multiple linear regression analysis was performed on each network metric between the NMO and control groups. RESULTS: The NMO patients exhibited abnormal small-world network properties, as indicated by increased normalized characteristic path length, increased normalized clustering and increased small-worldness. Furthermore, largely similar hub distributions of the WM structural networks were observed between NMO patients and healthy controls. However, regional efficiency in several brain areas of NMO patients was significantly reduced, which were mainly distributed in the default-mode, sensorimotor and visual systems. Furthermore, we have observed increased regional efficiency in a few brain regions such as the orbital parts of the superior and middle frontal and fusiform gyri. CONCLUSION: Although the NMO patients in this study had no discernible white matter T2 lesions in the brain, we hypothesize that the disrupted topological organization of WM networks provides additional evidence for subtle, widespread cerebral WM pathology in NMO.

  7. Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions.

    Directory of Open Access Journals (Sweden)

    Marta Subirà

    Full Text Available Obsessive-compulsive disorder (OCD is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30 and reactive (n = 65 sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally, while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.

  8. Individual Pulmonary Vein Atresia in Adults: Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyoung Nam; Kim, Young Tong; Cho, Sung Sik [Cheonan Hospital, SoonchunhyangUniversity College of Medicine, Cheonan (Korea, Republic of)

    2011-06-15

    We present two cases of individual pulmonary vein atresia without vestige of an involved pulmonary vein. On CT, we noted the absence or interruption of normal pulmonary venous structures, and the presence of abnormal vascular structures that represented collaterals for the involved lung parenchyma. On angiography, the artertic pulmonary vein was found to drain into the other ipsilateral pulmonary veins through the collaterals.

  9. Altered structural and functional thalamocortical networks in secondarily generalized extratemporal lobe seizures

    Directory of Open Access Journals (Sweden)

    Syu-Jyun Peng

    2017-01-01

    Full Text Available Structural and functional abnormalities in the thalamocortical network in primary generalized epilepsies or mesial temporal lobe epilepsy have recently been identified by voxel-wise analyses of neuroimaging. However, evidence is needed regarding the profiles of the thalamocortical network in patients with secondarily generalized seizures from focal neocortical sources. We used high-resolution T1-weighted, diffusion-tensor and resting-state functional MR imaging (rs-fMRI to examine 16 patients with secondarily generalized extratemporal lobe seizures and 16 healthy controls. All the patients were medically effective and MRI-negative. Using whole brain voxel-based morphometry (VBM to compare the patients with the normal controls, we observed significantly decreased gray matter (GM density in the thalamus and 3 frontal gyri and significantly reduced white matter (WM fractional anisotropy (FA in the bilateral anterior corona radiata of the patients. Alterations in the thalamocortical functional connectivity with different cortices were identified by the rs-fMRI analysis seeding of the whole thalamus. The prefrontal gyri with the greatest functional connectivity were also traced by seeding a sub-thalamic region that is demarcated in an atlas, in which the thalamic parcellation is based on the WM connectivity to the cortices. This sub-thalamic region anatomically contains the mediodorsal thalamic nucleus where, concordantly, there was a significant decrease in thalamic GM density in the VBM study. In contrast to the negative correlation between the disease duration and reduced thalamic densities and subcortical FA values, the strength of the functional thalamocortical connectivity had a paradoxical correlation. Our results conclusively indicate that generalized seizures with a focal cortical source are associated with structural and functional alterations in the thalamocortical network.

  10. Do neural tube defects lead to structural alterations in the human bladder?

    Science.gov (United States)

    Pazos, Helena M F; Lobo, Márcio Luiz de P; Costa, Waldemar S; Sampaio, Francisco J B; Cardoso, Luis Eduardo M; Favorito, Luciano Alves

    2011-05-01

    Anencephaly is the most severe neural tube defect in human fetuses. The objective of this paper is to analyze the structure of the bladder in anencephalic human fetuses. We studied 40 bladders of normal human fetuses (20 male and 20 female, aged 14 to 23 WPC) and 12 bladders of anencephalic fetuses (5 male and 7 female, aged 18 to 22 WPC). The bladders were removed and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in sections. Data were expressed as volumetric density (Vv-%). The images were captured with Olympus BX51 microscopy and Olympus DP70 camera. The stereological analysis was done using the software Image Pro and Image J. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p<0.05). We observed a significant increase (p<0.0001) in the Vv of collagen in the bladders of anencephalic fetuses (69.71%) when compared to normal fetuses (52.74%), and a significant decrease (p<0.0001) in the Vv of smooth muscle cells in the bladders of anencephalic fetuses (23.96%) when compared to normal fetuses (38.35%). The biochemical analyses showed a higher concentration of total collagen in the bladders of anencephalic fetuses (37354 µg/mg) when compared to normal fetuses (48117 µg/mg, p<0.02). The structural alterations of the bladder found in this study may suggest the existence of functional alterations in the bladder of anencephalic human fetuses.

  11. Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus).

    Science.gov (United States)

    Bouch, Sheena; Harding, Richard; O'Reilly, Megan; Wood, Lisa G; Sozo, Foula

    2016-01-01

    Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ) could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J) breathed either 65% O2 (hyperoxia) or room air from birth until postnatal day 7 (P7d); some underwent necropsy at P7d and others were raised in room air until adulthood (P56d). In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water) from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC), markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression), inflammation (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression), collagen (COL) and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d) and leukocytes in BALF (at P56d). At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects of

  12. Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus.

    Directory of Open Access Journals (Sweden)

    Sheena Bouch

    Full Text Available Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF. These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J breathed either 65% O2 (hyperoxia or room air from birth until postnatal day 7 (P7d; some underwent necropsy at P7d and others were raised in room air until adulthood (P56d. In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC, markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression, inflammation (interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α expression, collagen (COL and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d and leukocytes in BALF (at P56d. At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects

  13. Reperfusion pulmonary edema

    International Nuclear Information System (INIS)

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B.

    1989-01-01

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B 4 and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability

  14. Different methods to alter surface morphology of high aspect ratio structures

    Energy Technology Data Exchange (ETDEWEB)

    Leber, M., E-mail: moritz.leber@utah.edu [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Shandhi, M.M.H. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Hogan, A. [Blackrock Microsystems, Salt Lake City, UT (United States); Solzbacher, F. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Bhandari, R.; Negi, S. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT (United States); Blackrock Microsystems, Salt Lake City, UT (United States)

    2016-03-01

    Graphical abstract: Surface engineering of high aspect ratio silicon structures. - Highlights: • Multiple roughening techniques for high aspect ratio devices were investigated. • Modification of surface morphology of high aspect ratio silicon devices (1:15). • Decrease of 76% in impedance proves significant increase in surface area. - Abstract: In various applications such as neural prostheses or solar cells, there is a need to alter the surface morphology of high aspect ratio structures so that the real surface area is greater than geometrical area. The change in surface morphology enhances the devices functionality. One of the applications of altering the surface morphology is of neural implants such as the Utah electrode array (UEA) that communicate with single neurons by charge injection induced stimulation or by recording electrical neural signals. For high selectivity between single cells of the nervous system, the electrode surface area is required to be as small as possible, while the impedance is required to be as low as possible for good signal to noise ratios (SNR) during neural recording. For stimulation, high charge injection and charge transfer capacities of the electrodes are required, which increase with the electrode surface. Traditionally, researchers have worked with either increasing the roughness of the existing metallization (platinum grey, black) or other materials such as Iridium Oxide and PEDOT. All of these previously investigated methods lead to more complicated metal deposition processes that are difficult to control and often have a critical impact on the mechanical properties of the metal films. Therefore, a modification of the surface underneath the electrode's coating will increase its surface area while maintaining the standard and well controlled metal deposition process. In this work, the surfaces of the silicon micro-needles were engineered by creating a defined microstructure on the electrodes surface using several

  15. Tumor necrosis factor-like weak inducer of apoptosis regulates quadriceps muscle atrophy and fiber-type alteration in a rat model of chronic obstructive pulmonary disease

    OpenAIRE

    Lu, Jun-Juan; Wang, Qing; Xie, Li Hua; Zhang, Qiang; Sun, Sheng Hua

    2017-01-01

    Background In chronic obstructive pulmonary disease (COPD), weakness and muscle mass loss of the quadriceps muscle has been demonstrated to predict survival and mortality rates of patients. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), as a member of the TNF superfamily, has recently been identified as a key regulator of skeletal muscle wasting and metabolic dysfunction. So our aim was to study the role of TWEAK during quadriceps muscle atrophy and fiber-type transformat...

  16. Congenital diaphragmatic hernia-associated pulmonary hypertension.

    Science.gov (United States)

    Harting, Matthew T

    2017-06-01

    Congenital diaphragmatic hernia (CDH) is a complex entity wherein a diaphragmatic defect allows intrathoracic herniation of intra-abdominal contents and both pulmonary parenchymal and vascular development are stifled. Pulmonary pathology and pathophysiology, including pulmonary hypoplasia and pulmonary hypertension, are hallmarks of CDH and are associated with disease severity. Pulmonary hypertension (PH) is sustained, supranormal pulmonary arterial pressure, and among patients with CDH (CDH-PH), is driven by hypoplastic pulmonary vasculature, including alterations at the molecular, cellular, and tissue levels, along with pathophysiologic pulmonary vasoreactivity. This review addresses the basic mechanisms, altered anatomy, definition, diagnosis, and management of CDH-PH. Further, emerging therapies targeting CDH-PH and PH are explored. Published by Elsevier Inc.

  17. Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2:FiO2 Ratio Early After Major Burns.

    Science.gov (United States)

    Johansson, Joakim; Steinvall, Ingrid; Herwald, Heiko; Lindbom, Lennart; Sjöberg, Folke

    2015-01-01

    Leukocytes are activated systemically and their numbers increase soon after a burn followed by a rapid decline to low normal or subnormal levels, possibly by increased extravasation. Experimental data support that an important target for such extravasation is the lungs and that leukocytes when they adhere to endothelial cells cause an increase in vascular permeability. The authors investigated a possible relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in concentration of blood leukocytes after a burn. This is a prospective, exploratory, single-center study. The authors measured the dynamic changes of leukocytes in blood starting early after the burn, pulmonary vascular permeability index by thermodilution, and PaO2:FiO2-ratios in 20 patients during the first 21 days after a major burn (>20% TBSA%). Median TBSA was 40% interquartile range (IQR, 25-52) and full thickness burn 28% (IQR, 2-39). There was a correlation between the early (leukocytes and pulmonary failure early after burns.

  18. Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

    Science.gov (United States)

    2012-01-01

    Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality. Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals. The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems. PMID:23101436

  19. Assessing river regime alteration due to flood detention structures in dry and semi-dry regions

    Science.gov (United States)

    Yaraghi, Navid; Torabihaghighi, Ali; Ronkanen, Anna-Kaisa; Fazel, Nasim; Rossi, Pekka. M.; Klöve, Björn

    2017-04-01

    In dry and semi-dry climate, flood detention structures are used for flood control and managed aquifer recharge. These damps basin runoff response decreasing the maximum flows and increasing the runoff duration through wet seasons. In this study, a framework to quantify the role of flood detention dams in headwater tributaries on total water balance of major basin and alteration of flow pattern in the main river has been presented. The study contains four main subroutines: rainfall-runoff model, reservoir flood routing, river analysis system and seepage analysis. The flood hydrographs with different return periods are estimated based on the climatic data and geomorphology of headwater basin. River flow analysis below the flood detention structure is carried out for two unsteady flow scenarios, first with the hydrographs of natural system (as pre-impact: quick flood with significant peak flow) and second the routed hydrographs due to detention process in the reservoir (as post-impact: damped flood lower peak with longer duration time). Two sets of dynamic water surface along the river (from the location of detention structure (x=0) to the confluence point with main river (x=L) are developed based on two hydrologic conditions as results of river analysis system. The results of framework define the impact of flood detention structure by comparing the timing, magnitude and variability of flow. The Kamal Abad artificial groundwater recharge in Mahrloo Lake basin in Southern Iran was selected as case study to demonstrate the application of the created framework. Through the probability analysis, the return period for hydrological drought would be compared in pre and post impact condition. The results clearly showed how embankments influence floods in tributaries and in some cases the flow reduced significantly and disappears in tributaries.

  20. Epileptic seizures induce structural and functional alterations on brain tissue membranes.

    Science.gov (United States)

    Turker, Sevgi; Severcan, Mete; Ilbay, Gul; Severcan, Feride

    2014-12-01

    Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audiogenetically susceptible epileptic seizures on structure, content and function of rat brain membrane components using Fourier transform infrared (FT-IR) spectroscopy. The findings have shown that both two types of epileptic seizures stimulate the variations in the molecular organization of membrane lipids, which have potential to influence the structures in connection with functions of membrane proteins. Moreover, less fluid lipid structure and a decline in content of lipids obtained from the ratio of CH3 asym/lipid, CH2 asym/lipid, CO/lipid, and olefinicCH/lipid and the areas of the PO2 symmetric and asymmetric modes were observed. Moreover, based on IR data the changes in the conformation of proteins were predicted by neural network (NN) analysis, and displayed as an increase in random coil despite a decrease in beta sheet. Depending on spectral parameters, we have successfully differentiated treated samples from the control by principal component analysis (PCA) and cluster analysis. In summary, FT-IR spectroscopy may offer promising attempt to identify compositional, structural and functional alterations in brain tissue membranes resulting from epileptic activities. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    Science.gov (United States)

    Rana, Surinder S; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K

    2016-01-01

    Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet.

  2. [The value of double contrast arthrotomography combined with cinematography in the diagnosis of functional and structural TMJ alterations].

    Science.gov (United States)

    Engelke, W; Grossniklaus, B; Sailer, H F

    1991-01-01

    Double contrast arthrotomography combined with cinematography as a diagnostic instrument establishing functional and structural TMJ alterations is evaluated for its diagnostic value and reliability within the chain of diagnostic measures applied. In 131 patients double-contrast arthrotomography was followed by a comprehensive history of joint problems, and verification of the clinical findings as well as the arthrographic diagnosis and the post-arthrographic TMJ alterations. Our interest was focussed, among others, on the question whether arthrography alone would have any therapeutic effect or produce an alteration in TMJ function.

  3. Structural and functional correlations in a large animal model of bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Organ, Louise; Bacci, Barbara; Koumoundouros, Emmanuel; Barcham, Garry; Milne, Marjorie; Kimpton, Wayne; Samuel, Chrishan; Snibson, Ken

    2015-07-31

    Idiopathic pulmonary fibrosis (IPF) is a severe and progressive respiratory disease with poor prognosis. Despite the positive outcomes from recent clinical trials, there is still no cure for this disease. Pre-clinical animal models are currently largely limited to small animals which have a number of shortcomings. We have previously shown that fibrosis is induced in isolated sheep lung segments 14 days after bleomycin treatment. This study aimed to determine whether bleomycin-induced fibrosis and associated functional changes persisted over a seven-week period. Two separate lung segments in nine sheep received two challenges two weeks apart of either, 3U bleomycin (BLM), or saline (control). Lung function in these segments was assessed by a wedged-bronchoscope procedure after bleomycin treatment. Lung tissue, and an ex vivo CT analysis were used to assess for the persistence of inflammation, fibrosis and collagen content in this model. Fibrotic changes persisted up to seven weeks in bleomycin-treated isolated lung segments (Pathology scores: bleomycin12.27 ± 0.07 vs. saline 4.90 ± 1.18, n = 9, p = 0.0003). Localization of bleomycin-induced injury and increased tissue density was confirmed by CT analysis (mean densitometric CT value: bleomycin -698 ± 2.95 Hounsfield units vs. saline -898 ± 2.5 Hounsfield units, p = 0.02). Masson's trichrome staining revealed increased connective tissue in bleomycin segments, compared to controls (% blue staining/total field area: 8.5 ± 0.8 vs. 2.1 ± 0.2 %, n = 9, p bleomycin-treated segments were significantly less compliant from baseline at 7 weeks post treatment compared to control-treated segments (2.05 ± 0.88 vs. 4.97 ± 0.79 mL/cmH20, n = 9, p = 0.002). There was also a direct negative correlation between pathology scores and segmental compliance. We show that there is a correlation between fibrosis and correspondingly poor lung function which persist for up to

  4. Diabetic polyneuropathy, sensory neurons, nuclear structure and spliceosome alterations: a role for CWC22

    Directory of Open Access Journals (Sweden)

    Masaki Kobayashi

    2017-03-01

    Full Text Available Unique deficits in the function of adult sensory neurons as part of their early neurodegeneration might account for progressive polyneuropathy during chronic diabetes mellitus. Here, we provide structural and functional evidence for aberrant pre-mRNA splicing in a chronic type 1 model of experimental diabetic polyneuropathy (DPN. Cajal bodies (CBs, unique nuclear substructures involved in RNA splicing, increased in number in diabetic sensory neurons, but their expected colocalization with survival motor neuron (SMN proteins was reduced – a mislocalization described in motor neurons of spinal muscular atrophy. Small nuclear ribonucleoprotein particles (snRNPs, also participants in the spliceosome, had abnormal multiple nuclear foci unassociated with CBs, and their associated snRNAs were reduced. CWC22, a key spliceosome protein, was aberrantly upregulated in diabetic dorsal root ganglia (DRG, and impaired neuronal function. CWC22 attenuated sensory neuron plasticity, with knockdown in vitro enhancing their neurite outgrowth. Further, axonal delivery of CWC22 siRNA unilaterally to locally knock down the aberrant protein in diabetic nerves improved aspects of sensory function in diabetic mice. Collectively, our findings identify subtle but significant alterations in spliceosome structure and function, including dysregulated CBs and CWC22 overexpression, in diabetic sensory neurons that offer new ideas regarding diabetic sensory neurodegeneration in polyneuropathy.

  5. Warming alters energetic structure and function but not resilience of soil food webs

    Science.gov (United States)

    Schwarz, Benjamin; Barnes, Andrew D.; Thakur, Madhav P.; Brose, Ulrich; Ciobanu, Marcel; Reich, Peter B.; Rich, Roy L.; Rosenbaum, Benjamin; Stefanski, Artur; Eisenhauer, Nico

    2017-12-01

    Climate warming is predicted to alter the structure, stability, and functioning of food webs1-5. Yet, despite the importance of soil food webs for energy and nutrient turnover in terrestrial ecosystems, the effects of warming on these food webs—particularly in combination with other global change drivers—are largely unknown. Here, we present results from two complementary field experiments that test the interactive effects of warming with forest canopy disturbance and drought on energy flux in boreal-temperate ecotonal forest soil food webs. The first experiment applied a simultaneous above- and belowground warming treatment (ambient, +1.7 °C, +3.4 °C) to closed-canopy and recently clear-cut forest, simulating common forest disturbance6. The second experiment crossed warming with a summer drought treatment (-40% rainfall) in the clear-cut habitats. We show that warming reduces energy flux to microbes, while forest canopy disturbance and drought facilitates warming-induced increases in energy flux to higher trophic levels and exacerbates the reduction in energy flux to microbes, respectively. Contrary to expectations, we find no change in whole-network resilience to perturbations, but significant losses in ecosystem functioning. Warming thus interacts with forest disturbance and drought, shaping the energetic structure of soil food webs and threatening the provisioning of multiple ecosystem functions in boreal-temperate ecotonal forests.

  6. Aspirin-mediated acetylation induces structural alteration and aggregation of bovine pancreatic insulin.

    Science.gov (United States)

    Yousefi, Reza; Taheri, Behnaz; Alavi, Parnian; Shahsavani, Mohammad Bagher; Asadi, Zahra; Ghahramani, Maryam; Niazi, Ali; Alavianmehr, Mohammad Mehdi; Moosavi-Movahedi, Ali Akbar

    2016-01-01

    The simple aggregation of insulin under various chemical and physical stresses is still an important challenge for both pharmaceutical production and clinical formulation. In the storage form, this protein is subjected to various chemical modifications which alter its physicochemical and aggregation properties. Aspirin (acetylsalicylic acid) which is the most widely used medicine worldwide has been indicated to acetylate a large number of proteins both in vitro and in vivo. In this study, as insulin treated with aspirin at 37°C, a significant level of acetylation was observed by flourescamine and o-phthalaldehyde assay. Also, different spectroscopic techniques, gel electrophoresis, and microscopic assessment were applied to compare the structural variation and aggregation/fibrillation propensity among acetylated and non-acetylated insulin samples. The results of spectroscopic assessments elucidate that acetylation induces insulin unfolding which is accompanied with the exposure of protein hydrophobic patches, a transition from alpha-helix to beta-sheet and increased propensity of the protein for aggregation. The kinetic studies propose that acetylation increases aggregation rate of insulin under both thermal and chemical stresses. Also, gel electrophoresis and dynamic light scattering experiments suggest that acetylation induces insulin oligomerization. Additionally, the results of Thioflavin T fluorescence study, Congo red absorption assessment, and microscopic analysis suggest that acetylation with aspirin enhances the process of insulin fibrillation. Overall, the increased susceptibility of acetylated insulin for aggregation may reflect the fact that this type of modification has significant structural destabilizing effect which finally makes the protein more vulnerable for pathogenic aggregation/fibrillation.

  7. CHOROIDAL STRUCTURE ALTERED BY DEGENERATION OF RETINA IN EYES WITH RETINITIS PIGMENTOSA.

    Science.gov (United States)

    Kawano, Hiroki; Sonoda, Shozo; Saito, Shiro; Terasaki, Hiroto; Sakamoto, Taiji

    2017-11-01

    To compare the structural characteristics of the choroid in the areas with greater retinal degeneration to the areas with less retinal degeneration in eyes with retinitis pigmentosa (RP). Patients with RP who had a hyperautofluorescent ring were studied. The choroidal images obtained by enhanced depth imaging optical coherence tomography located 7,500 μm from the optic disk in the horizontal plane were analyzed. The cross-sectional areas of the total, luminal, and stromal choroid were measured. The area within the hyperautofluorescent ring was defined as the "central choroid" with less retinal degeneration. Thirty-seven eyes of 24 patients with RP were studied. The cross-sectional area of the total choroid was significantly smaller in the RP eyes than that in the control eyes (P < 0.01). The stromal areas of the choroid were not significantly different from the stromal areas of the controls. However, the luminal areas of the nasal and temporal choroid in the RP eyes were significantly smaller than that of the corresponding areas of the controls. The ratio of the luminal area to the total choroidal area in the central choroid was 68.0 ± 3.3% which was significantly larger than that of the nasal or the temporal choroid (P < 0.01). The choroidal structure is differentially altered in eyes with RP. The changes in the choroid were dependent on whether they were located within the hyperautofluorescent or outside the hyperautofluorescent ring.

  8. Structural alterations in the male reproductive system of the freshwater crayfish, Cherax quadricarinatus (Decapoda, Parastacidae).

    Science.gov (United States)

    Bugnot, Ana B; López Greco, Laura S

    2009-10-01

    No diseases affecting reproductive performance have been previously reported in freshwater crayfishes. This study aims to characterise one reproductive system abnormality found in males of Cherax quadricarinatus reared in captivity. Fifteen adult males of C. quadricarinatus (70-110 g) were purchased from San Mateo S.A. farm (Entre Ríos, Argentina) each season during 2007. Macroscopic analysis showed that 26.6% of the animals sacrificed in winter presented brownish distal vasa deferentia. Histological analysis showed different levels of structural abnormality in the epithelium of the vasa deferentia and spermatophore. Granular and hyaline haemocytes were identified within the vasa deferentia but no significant differences were found in the sperm count between normal and brownish vas deferens. Histological analysis of the crayfishes sacrificed in autumn also showed these modifications in 22% of the animals, however, they did not show the brownish colour under macroscopic analysis. The similarities between the male reproductive system syndrome in shrimps and the abnormalities found in C. quadricarinatus are notable. An unspecific response to thermic stress is a possible explanation of these structural alterations.

  9. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

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    Amal Abdussalam Ali A. Hmaid

    2018-03-01

    Full Text Available Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C or cold (4 ± 1 °C and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis. Keywords: Cardiomyocyte, Cardiac hypertrophy, l-Arginine, l-NAME, Myocardium

  10. Human hemoglobin structural and functional alterations and heme degradation upon interaction with benzene: A spectroscopic study.

    Science.gov (United States)

    Hosseinzadeh, Reza; Moosavi-Movahedi, Ali Akbar

    2016-03-15

    Here, the effect of benzene on hemoglobin structure, stability and heme prosthetic group integrity was studied by different methods. These included UV-vis absorption spectrophotometry, normal and synchronous fluorescence techniques, and differential scanning calorimetry (DSC). Our results indicated that benzene has high hemolytic potential even at low concentrations. The UV-vis spectroscopic results demonstrated that benzene altered both the globin chain and the heme prosthetic group of hemoglobin increasing met- and deoxy-Hb, while decreasing oxy-Hb. However, with increasing benzene the concentration of all species decreased due to heme destruction. The spectrophotometric results show that benzene has a high potential for penetrating the hydrophobic pocket of hemoglobin. These results were consistent with the molecular docking simulation results of benzene-hHb. Aggregation and thermal denaturation studies show that the increased benzene concentration induced hemoglobin aggregation with a decrease in stability, which is consistent with the DSC results. Conventional fluorescence spectroscopy revealed that the heme degradation species were produced in the presence of benzene. The results of constant wavelength synchronous fluorescence spectroscopy (CWSFS) indicated that at least five heme-degraded species were produced. Together, our results indicated that benzene has adverse effects on hemoglobin structure and function, and heme degradation. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Identification of glycan structure alterations on cell membrane proteins in desoxyepothilone B resistant leukemia cells.

    Science.gov (United States)

    Nakano, Miyako; Saldanha, Rohit; Göbel, Anja; Kavallaris, Maria; Packer, Nicolle H

    2011-11-01

    Resistance to tubulin-binding agents used in cancer is often multifactorial and can include changes in drug accumulation and modified expression of tubulin isotypes. Glycans on cell membrane proteins play important roles in many cellular processes such as recognition and apoptosis, and this study investigated whether changes to the glycan structures on cell membrane proteins occur when cells become resistant to drugs. Specifically, we investigated the alteration of glycan structures on the cell membrane proteins of human T-cell acute lymphoblastic leukemia (CEM) cells that were selected for resistance to desoxyepothilone B (CEM/dEpoB). The glycan profile of the cell membrane glycoproteins was obtained by sequential release of N- and O-glycans from cell membrane fraction dotted onto polyvinylidene difluoride membrane with PNGase F and β-elimination respectively. The released glycan alditols were analyzed by liquid chromatography (graphitized carbon)-electrospray ionization tandem MS. The major N-glycan on CEM cell was the core fucosylated α2-6 monosialo-biantennary structure. Resistant CEM/dEpoB cells had a significant decrease of α2-6 linked sialic acid on N-glycans. The lower α2-6 sialylation was caused by a decrease in activity of β-galactoside α2-6 sialyltransferase (ST6Gal), and decreased expression of the mRNA. It is clear that the membrane glycosylation of leukemia cells changes during acquired resistance to dEpoB drugs and that this change occurs globally on all cell membrane glycoproteins. This is the first identification of a specific glycan modification on the surface of drug resistant cells and the mechanism of this downstream effect on microtubule targeting drugs may offer a route to new interventions to overcome drug resistance.

  12. Structural Alterations within Cerebellar Circuitry Are Associated with General Liability for Common Mental Disorders

    Science.gov (United States)

    Romer, Adrienne L.; Knodt, Annchen R.; Houts, Renate; Brigidi, Bartholomew D.; Moffitt, Terrie E.; Caspi, Avshalom; Hariri, Ahmad R.

    2017-01-01

    Accumulating mental health research encourages a shift in focus towards transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology – sometimes called the ‘p factor’ – that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the ‘p factor’ contributes to risk. Here we first replicate the ‘p factor’ using cross-sectional data from a volunteer sample of 1,246 university students, and then, using high-resolution multimodal structural neuroimaging, demonstrate that individuals with higher ‘p factor’ scores show reduced structural integrity of white matter pathways, as indexed by lower fractional anisotropy values, uniquely within the pons. Whole-brain analyses further revealed that higher ‘p factor’ scores are associated with reduced gray matter volume in the occipital lobe and left cerebellar lobule VIIb, which is functionally connected with prefrontal regions supporting cognitive control. Consistent with the preponderance of cerebellar afferents within the pons, we observed a significant positive correlation between the white matter integrity of the pons and cerebellar gray matter volume associated with higher ‘p factor’ scores. The results of our analyses provide initial evidence that structural alterations in cortico-cerebellar circuitry supporting core functions related to the basic integration, coordination, and monitoring of information may contribute to a general liability for common mental disorders. PMID:28397842

  13. Pulmonary Hypertension and Pulmonary Vasodilators.

    Science.gov (United States)

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Pulmonary Edema

    Science.gov (United States)

    ... by viral infections such as the hantavirus and dengue virus. Lung injury. Pulmonary edema can occur after ... it may be fatal even if you receive treatment. Prevention Pulmonary edema is not always preventable, but ...

  15. Pulmonary Embolism

    Science.gov (United States)

    A pulmonary embolism is a sudden blockage in a lung artery. The cause is usually a blood clot in ... loose and travels through the bloodstream to the lung. Pulmonary embolism is a serious condition that can ...

  16. Pulmonary Fibrosis

    Science.gov (United States)

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue gets thick ... blood may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective ...

  17. HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells.

    Science.gov (United States)

    Frencher, James T; Shen, Hongbo; Yan, Lin; Wilson, Jessica O; Freitag, Nancy E; Rizzo, Alicia N; Chen, Crystal Y; Chen, Zheng W

    2014-12-01

    Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactA ΔGCPE: prfA* mutant. The HMBPP-deficient ΔGCPE: mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention. © 2014 Society for Leukocyte Biology.

  18. HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells

    Science.gov (United States)

    Frencher, James T.; Shen, Hongbo; Yan, Lin; Wilson, Jessica O.; Freitag, Nancy E.; Rizzo, Alicia N.; Chen, Crystal Y.; Chen, Zheng W.

    2014-01-01

    Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactAΔgcpE prfA* mutant. The HMBPP-deficient ΔgcpE mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention. PMID:25114162

  19. Structural Chromosomal Alterations Induced by Dietary Bioflavonoids in Fanconi Anemia Lymphocytes

    Directory of Open Access Journals (Sweden)

    Gonzalo Guevara

    2007-06-01

    Full Text Available IntroductionFanconi anemia is an autosomal recessive diseasecharacterized by a variety of congenital abnormalities,progressive bone marrow failure,increased chromosomal instability and higherrisk to acute myeloid leukemia, solid tumors. Thisentity can be considered an appropriate biologicalmodel to analyze natural substances with possiblegenotoxic effect. The aims of this study wereto describe and quantify structural chromosomalaberrations induced by 5 flavones, 2 isoflavonesand a topoisomerase II chemotherapeutic inhibitorin Fanconi anemia lymphocytes in order todetermine chromosomal numbers changes and/or type of chromosomal damage.Materials and methodsChromosomes stimulated by phytohaemagglutininM, from Fanconi anemia lymphocytes,were analysed by conventional cytogenetic culture.For each chemical substance and controls,one hundred metaphases were evaluated. Chromosomalalterations were documented by photographyand imaging analyzer. To statisticalanalysis was used chi square test to identify significantdifferences between frequencies of chromosomaldamage of basal and exposed cellcultured a P value less than 0.05.ResultsThere were 431 chromosomal alterations in1000 metaphases analysed; genistein was themore genotoxic bioflavonoid, followed in descendentorder by genistin, fisetin, kaempferol,quercetin, baicalein and miricetin. Chromosomalaberrations observed were: chromatidbreaks, chromosomal breaks, cromatid andchromosomal gaps, quadriratials exchanges,dicentrics chromosome and complex rearrangements.ConclusionBioflavonoids as genistein, genistin and fisetin,which are commonly present in the human diet,showed statistical significance in the number ofchromosomal aberrations in Fanconi anemialymphocytes, regarding the basal damage.

  20. Functionally Distinct Tendons From Elastin Haploinsufficient Mice Exhibit Mild Stiffening and Tendon-Specific Structural Alteration.

    Science.gov (United States)

    Eekhoff, Jeremy D; Fang, Fei; Kahan, Lindsey G; Espinosa, Gabriela; Cocciolone, Austin J; Wagenseil, Jessica E; Mecham, Robert P; Lake, Spencer P

    2017-11-01

    Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix (IFM). While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e., vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e.g., positional, energy-storing) remains unknown. Therefore, this study purposed to evaluate the role of elastin in the mechanical properties and collagen alignment of functionally distinct supraspinatus tendons (SSTs) and Achilles tendons (ATs) from elastin haploinsufficient (HET) and wild type (WT) mice. Despite the significant decrease in elastin in HET tendons, a slight increase in linear stiffness of both tendons was the only significant mechanical effect of elastin haploinsufficiency. Additionally, there were significant changes in collagen nanostructure and subtle alteration to collagen alignment in the AT but not the SST. Hence, elastin may play only a minor role in tendon mechanical properties. Alternatively, larger changes to tendon mechanics may have been mitigated by developmental compensation of HET tendons and/or the role of elastic fibers may be less prominent in smaller mouse tendons compared to the larger bovine and human tendons evaluated in previous studies. Further research will be necessary to fully elucidate the influence of various elastic fiber components on structure-function relationships in functionally distinct tendons.

  1. Hair structures are effectively altered during 810 nm diode laser hair epilation at low fluences.

    Science.gov (United States)

    Trelles, Mario A; Urdiales, Fernándo; Al-Zarouni, Marwan

    2010-03-01

    Diode lasers with high fluence and cooling technology are effective at removing unwanted hair but are also associated with discomfort and morbidity, especially when treating dark or tanned skins. Thirty patients with skin phototypes IV and V (range: 23-62 years of age; average: 39 years) underwent a single hair removal treatment using a new diode laser (810 nm) technology that incorporates low fluence but very high average power. The treatment technique employed multiple, in-motion, repetitive laser passes on a 100 cm(2) area of the skin. A 5mm punch biopsy was carried out before and after a single treatment. Tissue samples were harvested and stained with haematoxylin-eosin. The physical integrity of hair follicles was altered with inflammatory infiltrate, hair shaft detachment from its sheath, and perifollicular oedema, related to incipient necrosis. Low fluence but high average power diode laser technology yields significant changes in hair structure and architecture in patients with dark skin types. The procedure caused low levels of discomfort and was well tolerated.

  2. Structural alterations in the prefrontal cortex mediate the relationship between Internet gaming disorder and depressed mood.

    Science.gov (United States)

    Choi, Jihye; Cho, Hyun; Kim, Jin-Young; Jung, Dong Jin; Ahn, Kook Jin; Kang, Hang-Bong; Choi, Jung-Seok; Chun, Ji-Won; Kim, Dai-Jin

    2017-04-28

    Adaptive gaming use has positive effects, whereas depression has been reported to be prevalent in Internet gaming disorder (IGD). However, the neural correlates underlying the association between depression and Internet gaming remain unclear. Moreover, the neuroanatomical profile of the striatum in IGD is relatively less clear despite its important role in addiction. We found lower gray matter (GM) density in the left dorsolateral prefrontal cortex (DLPFC) in the IGD group than in the Internet gaming control (IGC) group and non-gaming control (NGC) group, and the GM density was associated with lifetime usage of Internet gaming, depressed mood, craving, and impulsivity in the gaming users. Striatal volumetric analysis detected a significant reduction in the right nucleus accumbens (NAcc) in the IGD group and its association with lifetime usage of gaming and depression. These findings suggest that alterations in the brain structures involved in the reward system are associated with IGD-related behavioral characteristics. Furthermore, the DLPFC, involved in cognitive control, was observed to serve as a mediator in the association between prolonged gaming and depressed mood. This finding may provide insight into an intervention strategy for treating IGD with comorbid depression.

  3. Altered gray matter organization in children and adolescents with ADHD: a structural covariance connectome study.

    Science.gov (United States)

    Griffiths, K R; Grieve, S M; Kohn, M R; Clarke, S; Williams, L M; Korgaonkar, M S

    2016-11-08

    Although multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organization in children and adolescents with ADHD. We generated anatomical networks based on covariance of gray matter volumes from 92 regions across the brain in children and adolescents with ADHD (n=34) and age- and sex-matched healthy controls (n=28). Using graph theory, we computed metrics that characterize both the global organization of anatomical networks (interconnectivity (clustering), integration (path length) and balance of global integration and localized segregation (small-worldness)) and their local nodal measures (participation (degree) and interaction (betweenness) within a network). Relative to Controls, ADHD participants exhibited altered global organization reflected in more clustering or network segregation. Locally, nodal degree and betweenness were increased in the subcortical amygdalae in ADHD, but reduced in cortical nodes in the anterior cingulate, posterior cingulate, mid temporal pole and rolandic operculum. In ADHD, anatomical networks were disrupted and reflected an emphasis on subcortical local connections centered around the amygdala, at the expense of cortical organization. Brains of children and adolescents with ADHD may be anatomically configured to respond impulsively to the automatic significance of stimulus input without having the neural organization to regulate and inhibit these responses. These findings provide a novel addition to our current understanding of the ADHD connectome.

  4. Local adaptation in Trinidadian guppies alters stream ecosystem structure at landscape scales despite high environmental variability

    Science.gov (United States)

    Simon, Troy N.; Bassar, Ronald D.; Binderup, Andrew J.; Flecker, Alex S.; Freeman, Mary C.; Gilliam, James F.; Marshall, Michael C.; Thomas, Steve A.; Travis, Joseph; Reznick, David N.; Pringle, Catherine M.

    2017-01-01

    While previous studies have shown that evolutionary divergence alters ecological processes in small-scale experiments, a major challenge is to assess whether such evolutionary effects are important in natural ecosystems at larger spatial scales. At the landscape scale, across eight streams in the Caroni drainage, we found that the presence of locally adapted populations of guppies (Poecilia reticulata) is associated with reduced algal biomass and increased invertebrate biomass, while the opposite trends were true in streams with experimentally introduced populations of non-locally adapted guppies. Exclusion experiments conducted in two separate reaches of a single stream showed that guppies with locally adapted phenotypes significantly reduced algae with no effect on invertebrates, while non-adapted guppies had no effect on algae but significantly reduced invertebrates. These divergent effects of phenotype on stream ecosystems are comparable in strength to the effects of abiotic factors (e.g., light) known to be important drivers of ecosystem condition. They also corroborate the results of previous experiments conducted in artificial streams. Our results demonstrate that local adaptation can produce phenotypes with significantly different effects in natural ecosystems at a landscape scale, within a tropical watershed, despite high variability in abiotic factors: five of the seven physical and chemical parameters measured across the eight study streams varied by more than one order of magnitude. Our findings suggest that ecosystem structure is, in part, an evolutionary product and not simply an ecological pattern.

  5. Thirty days of spaceflight does not alter murine calvariae structure despite increased Sost expression

    Directory of Open Access Journals (Sweden)

    Timothy R. Macaulay

    2017-12-01

    Full Text Available Previously our laboratory documented increases in calvaria bone volume and thickness in mice exposed to 15 days of spaceflight aboard the NASA Shuttle mission STS-131. However, the tissues were not processed for gene expression studies to determine what bone formation pathways might contribute to these structural adaptations. Therefore, this study was designed to investigate both the structural and molecular changes in mice calvariae after a longer duration of spaceflight. The primary purpose was to determine the calvaria bone volume and thickness of mice exposed to 30 days of spaceflight using micro-computed tomography for comparison with our previous findings. Because sclerostin, the secreted glycoprotein of the Sost gene, is a potent inhibitor of bone formation, our second aim was to quantify Sost mRNA expression using quantitative PCR. Calvariae were obtained from six mice aboard the Russian 30-day Bion-M1 biosatellite and seven ground controls. In mice exposed to 30 days of spaceflight, calvaria bone structure was not significantly different from that of their controls (bone volume was about 5% lower in spaceflight mice, p = 0.534. However, Sost mRNA expression was 16-fold (16.4 ± 0.4, p < 0.001 greater in the spaceflight group than that in the ground control group. Therefore, bone formation may have been suppressed in mice exposed to 30 days of spaceflight. Genetic responsiveness (e.g. sex or strain of animals or in-flight environmental conditions other than microgravity (e.g. pCO2 levels may have elicited different bone adaptations in STS-131 and Bion-M1 mice. Although structural results were not significant, this study provides biochemical evidence that calvaria mechanotransduction pathways may be altered during spaceflight, which could reflect vascular and interstitial fluid adaptations in non-weight bearing bones. Future studies are warranted to elucidate the processes that mediate these effects and the factors responsible

  6. Boldenone-induced apoptotic, structural, and functional alterations in the liver of rabbits

    Directory of Open Access Journals (Sweden)

    R.F. Mayada

    2015-03-01

    Full Text Available Boldenone undecylenate (BOL is an anabolic androgenic steroid used in livestock to improve growth and food conversion. This study investigated the actions of BOL on structure and functions of rabbit liver as well as the effects of its withdrawal. Eighteen mature male New Zealand rabbits were divided into 2 groups: Control group (n=6 were injected with 0.25 mL corn oil/kg body weight (BW, while BOL group (n=12 received 3 intramuscular injections, 2 wk apart, of BOL (4.5 mg/kg BW. Animals were scarified 1 d after last injection except for 6 rabbits from BOL group that served as the BOL-withdrawal group (4 wk after the 3rd injection. Intramuscular injection of BOL increased (P<0.05 malondialdehyde (MDA level, but markedly lowered activities of superoxide dismutase (SOD and catalase (CAT and reduced glutathione (GSH concentration compared to both control and BOL-withdrawal groups. Treatment with BOL significantly (P<0.05 increased serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST compared to the control group. BOL injection caused different histopathological alterations and apoptosis in liver, but these changes were less evident in the BOL-withdrawal group. Expression of p53 and tumour necrosis factor-α (TNF-α genes was up regulated in BOL compared to control group, while the expressions of p53 and TNF-α were down regulated in BOL-withdrawal group in comparison with BOL group. In conclusion, BOL injection induced structural and functional changes in the liver of rabbits, increasing oxidative stress and mediators of apoptosis such as ROS, p53 and TNF-α. All these parameters returned to near the control values after withdrawal.

  7. The Z mutation alters the global structural dynamics of α1-antitrypsin.

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    Victoria A Hughes

    Full Text Available α1-Antitrypsin (α1AT deficiency, the most common serpinopathy, results in both emphysema and liver disease. Over 90% of all clinical cases of α1AT deficiency are caused by the Z variant in which Glu342, located at the top of s5A, is replaced by a Lys which results in polymerization both in vivo and in vitro. The Glu342Lys mutation removes a salt bridge and a hydrogen bond but does not effect the thermodynamic stability of Z α1AT compared to the wild type protein, M α1AT, and so it is unclear why Z α1AT has an increased polymerization propensity. We speculated that the loss of these interactions would make the native state of Z α1AT more dynamic than M α1AT and that this change renders the protein more polymerization prone. We have used hydrogen/deuterium exchange combined with mass spectrometry (HXMS to determine the structural and dynamic differences between native Z and M α1AT to reveal the molecular basis of Z α1AT polymerization. Our HXMS data shows that the Z mutation significantly perturbs the region around the site of mutation. Strikingly the Z mutation also alters the dynamics of regions distant to the mutation such as the B, D and I helices and specific regions of each β-sheet. These changes in global dynamics may lead to an increase in the likelihood of Z α1AT sampling a polymerogenic structure thereby causing disease.

  8. Exposure to the endocrine disruptor nonylphenol alters structure and function of thyroid gland in rats.

    Science.gov (United States)

    Xi, Yue; Li, Dehua; San, Wei

    2013-08-10

    Nonylphenol (NP) is an estrogenic-like compound which can induce vitellogenin synthesis in males and immature teleostean species. Known as an endocrine disruptor, it has been reported to affect endocrine glands; however, little is known about its effects on thyroid function. The present study aimed to evaluate whether exposure to NP alters the structure and function of the thyroid gland of rats and/or the underlying mechanisms. Rats were gavaged with NP (40, 80 and 200 mg/kg/d) for 15 days. Serum levels of thyroid-stimulating hormone were determined by radioimmunoassay. Ultramicroscopic structure of follicular cells was examined by a transmission electron microscope. Histopathology was conducted with hematoxylin-eosin (HE) staining. We found that NP exposure induced a decrease in serum levels of free tetraiodothyronine (FT) 3 and FT4 while it induced an increase in serum levels of thyroid-stimulating hormone (TSH) in a dose-dependent manner. There was a negative correlation between different doses of NP with serum levels of FT3 and FT4 (FT4 r=-0.932; FT3 r=-0.926) and a positive correlation with serum levels of TSH (r=0.967). Histological and morphometric study in the NP-exposed group revealed dilation of endoplasmic reticulum into cystic in thyroid follicular cells. Mitochondrion was damaged in the 80 and 200 mg/kg/d groups. Exposure to NP may lead to thyroid dysfunction. It may be a potential contributor to thyroid disruption. © 2013 Elsevier B.V. All rights reserved.

  9. The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain.

    Science.gov (United States)

    Kim, Jae-Sung; Kroin, Jeffrey S; Li, Xin; An, Howard S; Buvanendran, Asokumar; Yan, Dongyao; Tuman, Kenneth J; van Wijnen, Andre J; Chen, Di; Im, Hee-Jeong

    2011-01-01

    Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.

  10. Inhaled nitric oxide improves lung structure and pulmonary hypertension in a model of bleomycin-induced bronchopulmonary dysplasia in neonatal rats.

    Science.gov (United States)

    Tourneux, Pierre; Markham, Neil; Seedorf, Gregory; Balasubramaniam, Vivek; Abman, Steven H

    2009-12-01

    Whether inhaled nitric oxide (iNO) prevents the development of bronchopulmonary dysplasia (BPD) in premature infants is controversial. In adult rats, bleomycin (Bleo) induces lung fibrosis and pulmonary hypertension, but the effects of Bleo on the developing lung and iNO treatment on Bleo-induced neonatal lung injury are uncertain. Therefore, we sought to determine whether early and prolonged iNO therapy attenuates changes of pulmonary vascular and alveolar structure in a model of BPD induced by Bleo treatment of neonatal rats. Sprague-Dawley rat pups were treated with Bleo (1 mg/kg ip daily) or vehicle (controls) from day 2 to 10, followed by recovery from day 11 to 19. Treatment groups received early (days 2-10), late (days 11-19), or prolonged iNO therapy (10 ppm; days 2-19). We found that compared with controls, Bleo increased right ventricular hypertrophy (RVH), and pulmonary arterial wall thickness, and reduced vessel density alveolarization. In each iNO treatment group, iNO decreased RVH (P rats, and that early and prolonged iNO therapy prevents right ventricle hypertrophy and pulmonary vascular remodeling and partially improves lung structure.

  11. Vascular narrowing in pulmonary arterial hypertension is heterogeneous: rethinking resistance

    NARCIS (Netherlands)

    Rol, N.; Timmer, E.M.; Faes, T.J.; Noordegraaf, A.V.; Grunberg, K.; Bogaard, H.J.; Westerhof, N.

    2017-01-01

    In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall

  12. New aspects on the structure of neutrophil extracellular traps from chronic obstructive pulmonary disease and in vitro generation.

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    Astrid Obermayer

    Full Text Available Polymorphonuclear neutrophils have in recent years attracted new attention due to their ability to release neutrophil extracellular traps (NETs. These web-like extracellular structures deriving from nuclear chromatin have been depicted in ambiguous roles between antimicrobial defence and host tissue damage. NETs consist of DNA strands of varying thickness and are decorated with microbicidal and cytotoxic proteins. Their principal structure has in recent years been characterised at molecular and ultrastructural levels but many features that are of direct relevance to cytotoxicity are still incompletely understood. These include the extent of chromatin decondensation during NET formation and the relative amounts and spatial distribution of the microbicidal components within the NET. In the present work, we analyse the structure of NETs found in induced sputum of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD using confocal laser microscopy and electron microscopy. In vitro induced NETs from human neutrophils serve for purposes of comparison and extended analysis of NET structure. Results demonstrate that COPD sputa are characterised by the pronounced presence of NETs and NETotic neutrophils. We provide new evidence that chromatin decondensation during NETosis is most extensive and generates substantial amounts of double-helix DNA in 'beads-on-a-string' conformation. New information is also presented on the abundance and location of neutrophil elastase (NE and citrullinated histone H3 (citH3. NE occurs in high densities in nearly all non-fibrous constituents of the NETs while citH3 is much less abundant. We conclude from the results that (i NETosis is an integral part of COPD pathology; this is relevant to all future research on the etiology and therapy of the disease; and that (ii release of 'beads-on-a-string' DNA studded with non-citrullinated histones is a common feature of in vivo NETosis; this is of relevance to

  13. A cluster randomised controlled trial evaluating the effectiveness of a structured pulmonary rehabilitation education programme for improving the health status of people with chronic obstructive pulmonary disease (COPD): The PRINCE Study protocol.

    Science.gov (United States)

    Murphy, Kathy; Casey, Dympna; Devane, Declan; Cooney, Adeline; McCarthy, Bernard; Mee, Lorraine; Nichulain, Martina; Murphy, Andrew W; Newell, John; O' Shea, Eamon

    2011-01-18

    A key strategy in improving care for people with chronic obstructive pulmonary disease (COPD) is the provision of pulmonary rehabilitation programmes. Pulmonary rehabilitation programmes have been successful in improving patients' sense of dyspnoea and Health Related Quality of Life. However, the effectiveness of structured education pulmonary rehabilitation programmes delivered at the level of the general practice on the health status of people with COPD remains uncertain and there is a need for a robust and fair assessment of this. The PRINCE study will evaluate the effectiveness of a Structured Education Pulmonary Rehabilitation Programme (SEPRP), delivered at the level of the general practice, on the health status of people with COPD. The PRINCE Trial is a two-armed, single blind cluster randomised trial conducted in the primary care setting in Ireland. Randomisation to control and intervention is at the level of the General Practice. Participants in the intervention arm will receive a SEPRP and those allocated to the control arm will receive usual care. Delivery of the SEPRP will be by a practice nurse and physiotherapist in the General Practice (GP) site. The primary outcome measure of the study will be health status as measured by the Chronic Respiratory Questionnaire (CRQ). Blinded outcome assessment will be undertaken at baseline and at twelve-fourteen weeks after completion of the programme. A comparison of outcomes between the intervention and control sites will be made to examine if differences exist and, if so, to what extent between control and experimental groups. Sample size calculations estimate that 32 practices with a minimum of 10 participants per practice are required, in total, to be randomised to control and intervention arms for power of at least 80% with alpha levels of 0.05, to determine a clinically significant change of 0.5 units in the CRQ. A cost effectiveness analysis will also be conducted. The results of this trial are directly

  14. A cluster randomised controlled trial evaluating the effectiveness of a structured pulmonary rehabilitation education programme for improving the health status of people with chronic obstructive pulmonary disease (COPD: The PRINCE Study protocol

    Directory of Open Access Journals (Sweden)

    Nichulain Martina

    2011-01-01

    Full Text Available Abstract Background A key strategy in improving care for people with chronic obstructive pulmonary disease (COPD is the provision of pulmonary rehabilitation programmes. Pulmonary rehabilitation programmes have been successful in improving patients' sense of dyspnoea and Health Related Quality of Life. However, the effectiveness of structured education pulmonary rehabilitation programmes delivered at the level of the general practice on the health status of people with COPD remains uncertain and there is a need for a robust and fair assessment of this. The PRINCE study will evaluate the effectiveness of a Structured Education Pulmonary Rehabilitation Programme (SEPRP, delivered at the level of the general practice, on the health status of people with COPD. Methods/Design The PRINCE Trial is a two-armed, single blind cluster randomised trial conducted in the primary care setting in Ireland. Randomisation to control and intervention is at the level of the General Practice. Participants in the intervention arm will receive a SEPRP and those allocated to the control arm will receive usual care. Delivery of the SEPRP will be by a practice nurse and physiotherapist in the General Practice (GP site. The primary outcome measure of the study will be health status as measured by the Chronic Respiratory Questionnaire (CRQ. Blinded outcome assessment will be undertaken at baseline and at twelve-fourteen weeks after completion of the programme. A comparison of outcomes between the intervention and control sites will be made to examine if differences exist and, if so, to what extent between control and experimental groups. Sample size calculations estimate that 32 practices with a minimum of 10 participants per practice are required, in total, to be randomised to control and intervention arms for power of at least 80% with alpha levels of 0.05, to determine a clinically significant change of 0.5 units in the CRQ. A cost effectiveness analysis will also be

  15. Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.

    Science.gov (United States)

    Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

    2014-06-15

    Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis. Copyright © 2014 the American Physiological Society.

  16. Compared study of the local structure of alteration products of SON 68 glass and natural gels; Etude comparee de la structure locale des produits d'alteration du verre SON 68 et de gels naturels

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrin, E

    2000-07-01

    This study is a contribution in the understanding of the long time behavior of alteration products of the glass SON 68, used to simulate the nuclear glass R7T7. The local structure around Zirconium and iron has been probed using X-ray absorption spectroscopy in altered surface layer of glass SON 68. Alteration products of this glass have been prepared for short (3 hours to 7 days) and long (17 months) time, using various indexes of saturation for the leaching solution with respect to the Si content of the glass (from 0 to 90 %). The evolution of the local structure around Fe has also been studied in recent and old natural ferric gels. Zr, Fe- L{sub 2,3} XANES and Zr, Fe-K EXAFS spectroscopies have shown that, in the pristine glass, these elements are connected to the polymeric network. Zr is found in an environment close to that of a zircon-silicate containing Na and Ca. Trivalent Fe is a network former. The leached layer of glass SON 68 is constituted of poorly ordered Zr-and Fe-(oxi-hydr)oxides that may have been formed by a mechanism of dissolution/precipitation; a relict phase with the same Zr local structure as that observed in the pristine glass, probably obtained thanks to in-situ solid condensation. The structural characteristics of the leached layer are observed from the first steps of alteration for Zr and Fe. Conversely to Fe, the structural status of Zr depends on the leaching kinetic as well as the contents of Ca and Si in the solid. Fe-K EXAFS results in recent natural ferri-hydrides present a clear structural similarity with that determined in glass SON 68 leached products. The study of old paleosols (between 1,800 and 200,000 years) has demonstrated the long time stability of ferric gels, although an increase of medium range order around Fe is seen. (author)

  17. Prenatal nicotine exposure evokes alterations of cell structure in hippocampus and somatosensory cortex.

    Science.gov (United States)

    Roy, Tara Sankar; Seidler, Frederic J; Slotkin, Theodore A

    2002-01-01

    Offspring of women who smoke during pregnancy show behavioral abnormalities, including increased incidence of attentional deficit, learning disabilities, and cognitive dysfunction. Animal models indicate that nicotine elicits changes in neural cell replication and differentiation, leading to deficits in synaptic neurochemistry and behavioral performance, many of which first emerge at adolescence. We evaluated cellular morphology and regional architecture in the juvenile and adolescent hippocampus and the somatosensory cortex in rats exposed to nicotine prenatally. Pregnant rats were given nicotine throughout gestation via minipump infusion of 2 mg/kg/day, a regimen that elicits nicotine plasma levels comparable with those found in smokers. On postnatal days 21 and 30, brains were perfusion-fixed, coronal slices were taken between the anterior commissure and median eminence, and the morphology of the dorsal hippocampus and somatosensory cortex was characterized. In the hippocampal CA3 region and dentate gyrus, we found a substantial decrease in cell size, with corresponding decrements in cell layer thickness, and increments in cell packing density. Smaller, transient changes were seen in CA1. In layer 5 of the somatosensory cortex, although there was no significant decrement in the average cell size, there was a reduction in the proportion of medium-sized pyramidal neurons, and an increase in the proportion of smaller, nonpyramidal cells. All regions showed elevated numbers of glia. Taken together with previous work on neurochemical and functional defects, these data demonstrate that prenatal nicotine exposure compromises neuronal maturation, leading to long-lasting alterations in the structure of key brain regions involved in cognition, learning, and memory.

  18. Structural myocardial alterations in diabetes and hypertension: the role of galectin-3.

    Science.gov (United States)

    Seferovic, Jelena P; Lalic, Nebojsa M; Floridi, Federico; Tesic, Milorad; Seferovic, Petar M; Giga, Vojislav; Lalic, Katarina; Jotic, Aleksandra; Jovicic, Snezana; Colak, Emina; Salerno, Gerardo; Cardelli, Patrizia; Di Somma, Salvatore

    2014-10-01

    Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

  19. Structure Activity Relationships of αv Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents

    Science.gov (United States)

    2014-01-01

    Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5. PMID:25408832

  20. Electronic cigarette vapor alters the lateral structure but not tensiometric properties of calf lung surfactant.

    Science.gov (United States)

    Przybyla, Rebecca J; Wright, Jason; Parthiban, Rajan; Nazemidashtarjandi, Saeed; Kaya, Savas; Farnoud, Amir M

    2017-11-17

    Despite their growing popularity, the potential respiratory toxicity of electronic cigarettes (e-cigarettes) remains largely unknown. One potential aspect of e-cigarette toxicity is the effect of e-cigarette vapor on lung surfactant function. Lung surfactant is a mixture of lipids and proteins that lines the alveolar region. The surfactant layer reduces the surface tension of the alveolar fluid, thereby playing a crucial role in lung stability. Due to their small size, particulates in e-cigarette vapor can penetrate the deep lungs and come into contact with the lung surfactant. The current study sought to examine the potential adverse effects of e-cigarette vapor and conventional cigarette smoke on lung surfactant interfacial properties. Infasurf ® , a clinically used and commercially available calf lung surfactant extract, was used as lung surfactant model. Infasurf ® films were spread on top of an aqueous subphase in a Langmuir trough with smoke particulates from conventional cigarettes or vapor from different flavors of e-cigarettes dispersed in the subphase. Surfactant interfacial properties were measured in real-time upon surface compression while surfactant lateral structure after exposure to smoke or vapor was examined using atomic force microscopy (AFM). E-cigarette vapor regardless of the dose and flavoring of the e-liquid did not affect surfactant interfacial properties. In contrast, smoke from conventional cigarettes had a drastic, dose-dependent effect on Infasurf ® interfacial properties reducing the maximum surface pressure from 65.1 ± 0.2 mN/m to 46.1 ± 1.3 mN/m at the highest dose. Cigarette smoke and e-cigarette vapor both altered surfactant microstructure resulting in an increase in the area of lipid multilayers. Studies with individual smoke components revealed that tar was the smoke component most disruptive to surfactant function. While both e-cigarette vapor and conventional cigarette smoke affect surfactant lateral structure

  1. Early ultrastructural alterations in adult dermatomyositis. Capillary abnormalities precede other structural changes in muscle

    NARCIS (Netherlands)

    de Visser, M.; Emslie-Smith, A. M.; Engel, A. G.

    1989-01-01

    In 6 adults with dermatomyositis, minimally weak or nonweak muscles that showed inconclusive light-microscopic alterations were examined by electron microscopy. In all 6 specimens, this revealed pathologic changes in endomysial capillaries. The endothelial cells harbored microtubular inclusions and

  2. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

    Directory of Open Access Journals (Sweden)

    Kerstin Pannek

    2014-01-01

    Conclusion: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

  3. Surfactant protein a in cystic fibrosis: supratrimeric structure and pulmonary outcome.

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    Matthias Griese

    Full Text Available BACKGROUND: The state of oligomerization of surfactant associated protein-A (SP-A monomers differs between individuals. This likely affects SP-A's functional properties and could thereby influence clinical status in patients with lung diseases. In this study we focus on SP-A structure in cystic fibrosis (CF compared to both healthy subjects and disease controls. METHODS: SP-A composition and function were assessed in both bronchoalveolar lavage (BAL fluid and serum of 46 CF patients with mild disease, 25 patients with chronic bronchitis and 22 healthy subjects by gel chromatography and a functional agglutination assay. Relation of SP-A agglutination ability to disease severity of the subjects was explored. RESULTS: SP-A was present in seven major oligomeric forms with the majority of SP-A being structurally organized as complex oligomeric forms. More complex oligomeric forms were associated with better SP-A function with regard to its agglutination ability. These forms were more frequently observed in BAL than in serum, but there were no differences between disease groups. In CF patients, more complex forms of SP-A were associated with better lung function. CONCLUSIONS: Organizational structure of SP-A affects its functional activity and is linked to disease severity in CF.

  4. Mutational destabilization of the critical interface water cluster in Scapharca dimeric hemoglobin: structural basis for altered allosteric activity.

    Science.gov (United States)

    Pardanani, A; Gambacurta, A; Ascoli, F; Royer, W E

    1998-12-04

    A cluster of interface ordered water molecules has been proposed to act as a key mediator of intersubunit communication in the homodimeric hemoglobin of Scapharca inaequivalvis. Mutations of Thr72 to Val and Ile, which lack the hydroxyl group to hydrogen bond the deoxy interface water molecules, result in sharply altered functional properties. We have determined the high resolution (1.6-1. 8 A) crystal structures of these two mutants in both the deoxygenated and CO-liganded states. These structures show minimal protein structural changes relative to the same native derivatives, despite greater than 40-fold increases in oxygen affinity. In the deoxy state of both mutants two water molecules at the periphery of the water cluster are lost, and the remaining cluster water molecules are destabilized. The CO-liganded structures show key differences between the two mutants including a more optimal interface packing involving Ile72 that acts to stabilize its high affinity (R) state. This additional stabilization allows rationalization of its lowered cooperativity within the context of a two-state model. These studies support a key role of ordered water in cooperative functioning and illustrate how subtle structural alterations can result in significantly altered functional properties in an allosteric molecule. Copyright 1998 Academic Press

  5. Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models.

    Science.gov (United States)

    Park, John E S; Lyon, Alexander R; Shao, Dongmin; Hector, Lauren R; Xu, Hua; O'Gara, Peter; Pinhu, Liao; Chambers, Rachel C; Wort, S John; Griffiths, Mark J D

    2014-12-01

    The burden of chronic heart failure (HF) is rising owing to an increased survivorship after myocardial infarction (MI). Pulmonary structural remodelling in patients with HF may protect against oedema while causing dyspnoea, the predominant symptom associated with HF. The cellular and molecular mechanisms underlying these processes in HF are poorly understood. We hypothesised that pulmonary venous hypertension (PVH) following MI provides a mechanical stimulus for structural remodelling of the lung via monocyte chemoattractant protein-1 (MCP-1). Human lung microvascular endothelial cells (HLMVEC) and Ea.Hy 926 cells exposed to cyclic mechanical strain (CMS) in vitro were analysed for MCP-1 expression and activation of signalling intermediates. HF was induced in Sprague-Dawley rats 16 weeks after MI; a cohort was rescued with AAV9.SERCA2a gene therapy to reduce PVH. HLMVEC and Ea.Hy 926 cells exposed to CMS upregulated MCP-1 gene expression and protein release in an extracellular-signal-regulated kinase (ERK) 1/2 dependent manner. Supernatants from these experiments stimulated fibroblast (human fetal lung fibroblast -1) and pulmonary artery smooth muscle cell proliferation and differentiation. Total lung collagen, a marker of structural remodelling, and MCP-1 gene expression were increased in the lungs of rats with post-MI HF. SERCA2a gene therapy that attenuated PVH after MI was associated with lower levels of lung collagen and MCP-1 gene expression in the lung. Mechanical strain associated with PVH may stimulate pulmonary structural remodelling through ERK 1/2 dependent induction of MCP-1. These findings provide insights into the pathophysiology of lung remodelling in HF and highlight novel, potential therapeutic targets. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Exploring patterns of alteration in Alzheimer’s disease brain networks: a combined structural and functional connectomics analysis

    Directory of Open Access Journals (Sweden)

    Fulvia Palesi

    2016-09-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the disconnection syndrome hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks in patients affected by AD and mild cognitive impairment (MCI. However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC. In the default mode network (DMN, that was the most affected, axonal loss and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN, disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN, neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI but also with subcortical alterations (revealed by diffusion MRI that extend beyond the areas primarily damaged by neurodegeneration, towards the support of an emerging concept of AD as a

  7. Pathogenesis of pulmonary emphysema – cellular and molecular events

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    Antonio Di Petta

    2010-06-01

    Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  8. Engineering tissue constructs to mimic native aortic and pulmonary valve leaflets' structures and mechanics

    Science.gov (United States)

    Masoumi, Nafiseh

    There are several disadvantages correlated with current heart valve replacement, including anticoagulation therapy for patients with mechanical valves and the low durability of bioprosthetic valves. The non-viable nature of such devices is a critical drawback especially for pediatric cases due to the inability of the graft to grow in vivo with the patients. A tissue engineered heart valve (TEHV) with remodeling and growth ability, is conceptually appealing to use in the surgical repair and could serve as a permanent replacements when operating for pediatric valvular lesions. It is critical that scaffolds for functional heart valve tissue engineering, be capable of mimicking the native leaflet's structure and mechanical properties at the time of implantation. Meanwhile, the scaffolds should be able to support cellular proliferation and native-like tissue formation as the TEHV remodels toward a scaffold-free state. Our overall hypothesis is that an "ideal" engineered construct, designed based on native leaflet's structure and mechanics, will complement a native heart valve leaflet in providing benchmarks for use in the design of clinically-applicable TEHV. This hypothesis was addressed through several experiments conducted in the present study. To establish a functional biomimetic TEHV, we developed scaffolds capable of matching the anisotropic stiffness of native leaflet while promoting native-like cell and collagen content and supporting the ECM generation. Scaffolds with various polymer contents (e.g., poly (glycerol sebacate) (PGS) and poly (epsilon-caprolactone) (PCL)) and structural designs (e.g., microfabricated and microfibrous scaffolds), were fabricated based on native leaflet's structure and mechanics. It was found that the tri-layered scaffold, designed with assembly of microfabricated PGS and microfibrous PGS/PCL was a functional leaflet capable of promoting tissue formation. Furthermore, to investigate the effect of cyclic stress and flexure

  9. Flood-Induced Surface Blooms Alter Deep Chlorophyll Maxima Community Structure in Lake Michigan.

    Science.gov (United States)

    Aguilar, C.; Cuhel, R. L.; Seline, L.

    2008-12-01

    Watershed-wide floods can bring increased nutrients and phytoplankton to receiving waters. This input can alter physical, chemical and phytoplankton community structure in a major way. Phytoplankton species composition and size distribution are key factors in their use as ecological indicators. Since 2003, phytoplankton communities in Lake Michigan have shifted from diatom and big cell (>10μm)- dominated to small cell picocyanobacteria-dominated phytoplankton (Quagga Mussels, dampened seasonal cycling of silicate indicated a basin-wide reduction of diatom production, and unicellular Cyanobacteria became dominant in deep chlorophyll maximum (DCM) zones. In the DCM, Synechococcus-like cells reached populations of at least 210,000 cells/ml. DCM chlorophyll (chl) remained similar (3-4μg/l) but late summer species composition changed dramatically to mostly 10μm fraction increased from previous years, and over 75% of the particulate Si was also in this size fraction. Because of the rapid sinking of diatoms during calm weather of late June-early July of 2008, particulate Si did not reach high values in surfaces waters (ca. 1.5μM) but remained at a consistently higher level than in 2007. Sinking of diatoms from the surface depleted chl in a progression from inshore to offshore during July 2008. In July surface chl was higher 40-70 km offshore than in the coastal zone. Surface phytoplankton waxed and waned in population density as if a wave or lens moved continuously further offshore, with sinking cells depleting the surface algae following behind the crest. In the wake, strong DCM populations with higher chl and particulate Si accumulated in the 30-45m zone at the bottom of the thermocline. However, in 2008 DCM zones, picocyanobacteria attained only 70,000 cells/mL, one-third of the same dates in 2007. The ratio of chlorophyll per Synechococcus cell in 2008 was about 5-fold higher than in 2007, corroborating microscopic observations of lowered picoplanktonic abundance

  10. Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

    Science.gov (United States)

    Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

    2018-02-20

    The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

  11. Adrenomedullin alleviates pulmonary artery collagen accumulation in rats with pulmonary hypertension induced by high blood flow.

    Science.gov (United States)

    Pang, Lulu; Qi, Jianguang; Gao, Yang; Jin, Hongfang; Du, Junbao

    2014-04-01

    Collagen accumulation is one of the important pathologic changes in the development of pulmonary hypertension. Previous research showed that adrenomedullin (ADM) mitigates the development of pulmonary hypertension. The present study explored the role of ADM in the development of pulmonary artery collagen accumulation induced by high pulmonary blood flow, by investigating the effect of ADM [1.5 μg/(kg h)] subcutaneously administered by mini-osmotic pump on pulmonary hemodynamics, pulmonary vascular structure and pulmonary artery collagen accumulation and synthesis in rats with high pulmonary blood flow induced by aortocaval shunting. The results showed that ADM significantly decreased mean pulmonary artery pressure (mPAP) and the ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+SP)], attenuated the muscularization of small pulmonary vessels and relative medial thickness (RMT) of pulmonary arteries in rats with high pulmonary blood flow. Meanwhile, ADM ameliorated pulmonary artery collagen deposition represented by a decrease in lung tissue hydroxyproline, collagens I and III content and pulmonary artery collagens I and III expression, reduced collagen synthesis represented by a decrease in lung tissue procollagens I and III mRNA expression. The results suggest that ADM plays a protective role in the development of pulmonary hypertension induced by high blood flow, by inhibiting pulmonary procollagen synthesis and alleviating pulmonary artery collagen accumulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Introduction to Pulmonary Fibrosis

    Science.gov (United States)

    ... Events Become An Advocate Volunteer Ways To Give Pulmonary Fibrosis www.lung.org > Lung Health and Diseases > ... Pulmonary Fibrosis > Introduction Share this page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is ...

  13. Learn About Pulmonary Fibrosis

    Science.gov (United States)

    ... Events Become An Advocate Volunteer Ways To Give Pulmonary Fibrosis www.lung.org > Lung Health and Diseases > Lung ... Pulmonary Fibrosis > Introduction Share this page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a ...

  14. Altered expression of cyclooxygenase-2, 12-lipoxygenase, inducible nitric oxide synthase-2 and surfactant protein D in lungs of patients with pulmonary injury caused by sulfur mustard.

    Science.gov (United States)

    Tahmasbpour, Eisa; Ghanei, Mostafa; Khor, Abolfazl; Panahi, Yunes

    2018-03-14

    Sulfur mustard (SM) is a strong alkylating toxicant that targets different organs, particularly human lung tissue. Change in genes expression is one of the molecular mechanisms of SM toxicity in damaged tissue. The purpose of this investigation is to characterize the expression of cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LO), inducible nitric oxide synthase 2 (iNOS2), and surfactant protein D (SFTPD) in lungs of patients who exposed to SM. Lung biopsies were provided from SM-exposed patients (n = 6) and controls (n = 5). Total RNA were extracted from all specimens and then cDNA was synthesized for each sample. Changes in gene expression were measured using RT 2 Profiler ™PCR Array. Pulmonary function tests revealed more obstructive and restrictive spirometric patterns among patients compared to the control group. Expression of COX-2 and 12-LO in the lung of patients was increased by 6.2555 (p = 0.004) and 6.2379-folds (p = 0.002), respectively. In contrast, expression of SF-D and iNOS genes was reduced by 8.5869-fold (p = 0.005) and 2.4466-folds (p = 0.011), respectively. Mustard lungs were associated with overexpression of COX-2 and 12-LO, which are responsible for inflammation, overproduction of free radicals and oxidative stress. Downregulation of iNOS2 and SF-D are probably the reason for lung disease and dysfunction among these patients. Therefore, the expression of these genes could be an important, routine part of the management of such patients.

  15. Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Chang, Wei-Ju; O'Connell, Neil E; Beckenkamp, Paula R; Alhassani, Ghufran; Liston, Matthew B; Schabrun, Siobhan M

    2018-04-01

    Chronic pain can be associated with movement abnormalities. The primary motor cortex (M1) has an essential role in the formulation and execution of movement. A number of changes in M1 function have been reported in studies of people with chronic pain. This review systematically evaluated the evidence for altered M1 structure, organization, and function in people with chronic pain of neuropathic and non-neuropathic origin. Database searches were conducted and a modified STrengthening the Reporting of OBservational studies in Epidemiology checklist was used to assess the methodological quality of included studies. Meta-analyses, including preplanned subgroup analyses on the basis of condition were performed where possible. Sixty-seven studies (2,290 participants) using various neurophysiological measures were included. There is conflicting evidence of altered M1 structure, organization, and function for neuropathic and non-neuropathic pain conditions. Meta-analyses provided evidence of increased M1 long-interval intracortical inhibition in chronic pain populations. For most measures, the evidence of M1 changes in chronic pain populations is inconclusive. This review synthesizes the evidence of altered M1 structure, organization, and function in chronic pain populations. For most measures, M1 changes are inconsistent between studies and more research with larger samples and rigorous methodology is required to elucidate M1 changes in chronic pain populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study

    Directory of Open Access Journals (Sweden)

    Dkhil MA

    2007-01-01

    Full Text Available Objective: The capillary changes at the initial stage of diabetes may show an angioarchitecture clearly different from those of later stages and,/or very severe glomerular change. However, the onset of alterations in the early phases is unclear. This study attempts to determine the functional and structural alterations of the glomerular wall and vesicles in the early stage of diabetes.Material and Methods: Twenty-five adult rats were used in this study. They were divided into two groups: the first group of five was used as a control .The second group of 20 (the experimental group was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, two months, and four months.Five rats at two months of age with hyperglycemia were treated with insulin for eight weeks. Renal tissues were prepared by routine technique for light and transmission electron microscopic evaluation. Results: By light microscopy after ten days of induced hyperglycemia, there were no structural modifications detected either in renal glomerular fine vessels or in the glomerular basement membrane of the glomerular capillaries. After two months, there was a moderate glomerular enlargement and dilatation of glomerular capillaries, afferent, and efferent arterioles. After four months, glomerular basement membrane thickening was the only structural alteration observed. Recovery of the glomerular alterations was observed after two months of treatment with insulin. Conclusion: In early stages of diabetes mellitus in rats, there was an increase in the diameter of glomerular vessels. In later stages of the disease, the reverse was seen, but insulin treatment had a positive role in reversing these changes in the study subjects.

  17. Alterations in upper limb muscle synergy structure in chronic stroke survivors

    Science.gov (United States)

    Rymer, William Z.; Perreault, Eric J.; Yoo, Seng Bum; Beer, Randall F.

    2013-01-01

    Previous studies in neurologically intact subjects have shown that motor coordination can be described by task-dependent combinations of a few muscle synergies, defined here as a fixed pattern of activation across a set of muscles. Arm function in severely impaired stroke survivors is characterized by stereotypical postural and movement patterns involving the shoulder and elbow. Accordingly, we hypothesized that muscle synergy composition is altered in severely impaired stroke survivors. Using an isometric force matching protocol, we examined the spatial activation patterns of elbow and shoulder muscles in the affected arm of 10 stroke survivors (Fugl-Meyer synergies were identified using non-negative matrix factorization. In both groups, muscle activation patterns could be reconstructed by combinations of a few muscle synergies (typically 4). We did not find abnormal coupling of shoulder and elbow muscles within individual muscle synergies. In stroke survivors, as in controls, two of the synergies were comprised of isolated activation of the elbow flexors and extensors. However, muscle synergies involving proximal muscles exhibited consistent alterations following stroke. Unlike controls, the anterior deltoid was coactivated with medial and posterior deltoids within the shoulder abductor/extensor synergy and the shoulder adductor/flexor synergy in stroke was dominated by activation of pectoralis major, with limited anterior deltoid activation. Recruitment of the altered shoulder muscle synergies was strongly associated with abnormal task performance. Overall, our results suggest that an impaired control of the individual deltoid heads may contribute to poststroke deficits in arm function. PMID:23155178

  18. Pulmonary endothelial cell activation during experimental acute kidney injury.

    Science.gov (United States)

    Feltes, Carolyn M; Hassoun, Heitham T; Lie, Mihaela L; Cheadle, Chris; Rabb, Hamid

    2011-08-01

    Acute kidney injury (AKI) leads to increased lung microvascular permeability, leukocyte infiltration, and upregulation of soluble inflammatory proteins in rodents. Most work investigating connections between AKI and pulmonary dysfunction, however, has focused on characterizing whole lung tissue changes associated with AKI. Studies at the cellular level are essential to understanding the molecular basis of lung changes during AKI. Given that the pulmonary microvascular barrier is functionally abnormal during AKI, we hypothesized that AKI induces a specific proinflammatory and proapoptotic lung endothelial cell (EC) response. Four and 24 h after kidney ischemia/reperfusion injury or bilateral nephrectomy, murine pulmonary ECs were isolated via tissue digestion followed by magnetic bead sorting. Purified lung ECs were analyzed for changes in mRNA expression using real-time SuperArray polymerase chain reaction analysis of genes related to EC function. In parallel experiments, confluent rat pulmonary microvascular ECs were treated with AKI or control serum to evaluate functional cellular alterations. Immunocytochemistry and FACS analysis of Annexin V/propidium iodide staining were used to evaluate cytoskeletal changes and promotion of apoptosis. Isolated murine pulmonary ECs exhibited significant changes in the expression of gene products related to inflammation, vascular reactivity, and programmed cell death. Further experiments using an in vitro rat pulmonary microvascular EC system revealed that AKI serum induced functional cellular changes related to apoptosis, including structural actin alterations and phosphatidylserine translocation. Analysis and segregation of both upregulated and downregulated genes into functional roles suggest that these transcriptional events likely participate in the transition to an activated proinflammatory and proapoptotic EC phenotype during AKI. Further mechanistic analysis of EC-specific events in the lung during AKI might reveal

  19. Pulmonary lymphatics and radiation

    International Nuclear Information System (INIS)

    Leeds, S.E.

    1976-01-01

    Knowledge of the anatomy and physiology of the respiratory system has been more difficult to acquire than that of other organ systems owing to the complexity of the respiratory function of the lungs and to the technical difficulties involved. This is especially true of the lymphatics of the lung and is illustrated by the fact that the first measurement of pulmonary lymph flow was in 1942 by Warren and Drinker. A review of the literature reveals that few experiments have been designed to study the pulmonary lymphatics per se in relation to the effects of external radiation or after the inhalation of radioactive particles. However, the documented involvement of hilar lymph nodes implies that the lung lymphatics have a role in transporting particles from the alveoli or malignant cells from the parenchyma. Information from clinical and experimental sources, though scattered, is fairly abundant and of value in assessing the role of the pulmonary lymphatics. Our method for collecting pulmonary lymph is presented. Studies on the pulmonary lymph flow in normal dogs and in dogs with experimental congestive heart failure are described. We irradiated (4000 to 5000 R) the medial one-third of both lungs of a series of dogs. The lymph flow of the lungs was measured immediately after the course of irradiation and after a period of about 5 months. Although lung biopsies showed characteristic radiation pneumonitis in many areas, alterations in the lung parenchyma were not quantitatively reflected in the pulmonary lymph flow either in the acute stage or after fibrosis had time to develop

  20. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

    Directory of Open Access Journals (Sweden)

    Chomiak Taylor

    2010-08-01

    Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.

  1. The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Won, Eunsoo

    2017-06-30

    Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid. Pro-inflammatory cytokines can also exert direct neurotoxic effects on specific brain regions. Previous imaging studies have reported associations between pro-inflammatory states and alterations in brain regions involved in emotional regulation, including the hippocampus, amygdala and anterior cingulate cortex. Alterations in structure and function of such brain areas due to the neurotoxic effects of increased inflammation may be associated with the pathophysiology of depression. This review focuses the influence of stress on neuroinflammation which may cause alterations in brain structure and function in MDD. Copyright © 2017. Published by Elsevier B.V.

  2. Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa.

    Science.gov (United States)

    Frank, Guido K; Shott, Megan E; Hagman, Jennifer O; Mittal, Vijay A

    2013-10-01

    The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. The authors used structural MR imaging to study gray and white matter volumes in women with current restricting-type anorexia nervosa (N=19), women recovered from restricting-type anorexia nervosa (N=24), women with bulimia nervosa (N=19), and healthy comparison women (N=24). All eating disorder groups exhibited increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manual tracing confirmed larger gyrus rectus volume, and volume predicted taste pleasantness ratings across all groups. Analyses also indicated other morphological differences between diagnostic categories. Antero-ventral insula gray matter volumes were increased on the right side in the anorexia nervosa and recovered anorexia nervosa groups and on the left side in the bulimia nervosa group relative to the healthy comparison group. Dorsal striatum volumes were reduced in the recovered anorexia nervosa and bulimia nervosa groups and predicted sensitivity to reward in all three eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas relative to the healthy comparison group. The results held when a range of covariates, such as age, depression, anxiety, and medications, were controlled for. Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value.

  3. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    OpenAIRE

    Rana, Surinder S.; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K.

    2016-01-01

    Background Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Methods Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes wer...

  4. Pulmonary Hypertension

    Science.gov (United States)

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... that carry blood from your heart to your lungs become hard and narrow. Your heart has to ...

  5. Mineralogical and structural transformations related to alterations in hydrothermal and climatological conditions of basic vulcanic rocks from northern Parana (Ribeirao Preto region, SP, Brazil)

    International Nuclear Information System (INIS)

    Goncalves, N.M.M.

    1987-01-01

    Detailed studies of the basic vulcanic rocks of northern Parana basin (Region of Ribeirao Preto, SP) reveled that these rocks were affected by pre-meteoric activity (hydrothermal alteration) before being exposed to the supergene system of alteration linked to the lithosphere/atmosphere interface. Mineralogical and structural transformation are studied. The appearance of sequential crystalline-chemical paragenesis in zones suggest that the hydrothermal activity occurred during two successives processes of alteration: the expulsion of the water from the rock during the later stages of magma cooling and the continous process of dissolution of the rock wall and the ionic diffusion involving the rock sistem of structural voids. The hydro-thermal action was followed by weathering action developing a thin 'front' of superficial alteration. This alteration system, can lead to the formation of three major levels of alteration horizons and superficial accumulations: alterites, glebular and suil surface materials. (C.D.G.) [pt

  6. [Primary pulmonary sarcomas].

    Science.gov (United States)

    Jakubcová, T; Jakubec, P

    2009-01-01

    Primary pulmonary sarcomas are rare diseases unlike lung carcinomas. The occurence of these sarcomas is between 0.013-0.40% of all malignant lung tumours. There are malignant mesenchymal tumours. They are flowing from the soft tissue of lung. The pulmonary sarcomas are heterogenic group with various biological behaviour. Their morfologic structure does not digger from the sarcomas of soft tissue. The primary pulmonary sarcomas occur more often in childhood and in young people unlike lung carcinomas. Radiation and some toxic substances are noted risk factors. Some gene mutations, infectious pathoghens and contraception have a possible impact on the origin of some types of the sarcomas. The current hypothesis is, that most of the sarcomas, if not all sarcomas, stem from primitive multipotent mesenchymal cell by malignant transformation in one or more lines. The diagnostic standard is biopsy from tumour with histologic and immunohistochemistry examination of a sample. The basic diagnostic problem is exclusion of a secondary origin of sarcomatic cells in the lung, because pulmonary metastasis of extrapulmonary sarcomas are more often than the primary pulmonary involvement.The optimal treatment is a resection of the tumour.The other therapeutic modalities are radiotherapy and chemotherapy, but results of these modalities are unsatisfactory. There are various chemotherapeutic regimes, monotherapy or combination regimes. The basic cytostatics are doxorubicine, iphosphamide, dacarbazine. Problems of the chemotherapy are high toxicity and relatively low curative effect about 20%.The first studies with biological treatment of the sarcomas of soft tissue have been published recently.This types of drugs could be a part of the complex management of these primary pulmonary tumours in the future. The primary pulmonary sarcomas have mostly aggresive course and often recur. Their prognosis is usually not very good. The survival median is 48 months and 5-years survival ranges

  7. Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers.

    Science.gov (United States)

    Alaei-Mahabadi, Babak; Bhadury, Joydeep; Karlsson, Joakim W; Nilsson, Jonas A; Larsson, Erik

    2016-11-29

    Tumor genomes are mosaics of somatic structural variants (SVs) that may contribute to the activation of oncogenes or inactivation of tumor suppressors, for example, by altering gene copy number amplitude. However, there are multiple other ways in which SVs can modulate transcription, but the general impact of such events on tumor transcriptional output has not been systematically determined. Here we use whole-genome sequencing data to map SVs across 600 tumors and 18 cancers, and investigate the relationship between SVs, copy number alterations (CNAs), and mRNA expression. We find that 34% of CNA breakpoints can be clarified structurally and that most amplifications are due to tandem duplications. We observe frequent swapping of strong and weak promoters in the context of gene fusions, and find that this has a measurable global impact on mRNA levels. Interestingly, several long noncoding RNAs were strongly activated by this mechanism. Additionally, SVs were confirmed in telomere reverse transcriptase (TERT) upstream regions in several cancers, associated with elevated TERT mRNA levels. We also highlight high-confidence gene fusions supported by both genomic and transcriptomic evidence, including a previously undescribed paired box 8 (PAX8)-nuclear factor, erythroid 2 like 2 (NFE2L2) fusion in thyroid carcinoma. In summary, we combine SV, CNA, and expression data to provide insights into the structural basis of CNAs as well as the impact of SVs on gene expression in tumors.

  8. Rainfall and hydrological stability alter the impact of top predators on food web structure and function.

    Science.gov (United States)

    Marino, Nicholas A C; Srivastava, Diane S; MacDonald, A Andrew M; Leal, Juliana S; Campos, Alice B A; Farjalla, Vinicius F

    2017-02-01

    Climate change will alter the distribution of rainfall, with potential consequences for the hydrological dynamics of aquatic habitats. Hydrological stability can be an important determinant of diversity in temporary aquatic habitats, affecting species persistence and the importance of predation on community dynamics. As such, prey are not only affected by drought-induced mortality but also the risk of predation [a non-consumptive effect (NCE)] and actual consumption by predators [a consumptive effect (CE)]. Climate-induced changes in rainfall may directly, or via altered hydrological stability, affect predator-prey interactions and their cascading effects on the food web, but this has rarely been explored, especially in natural food webs. To address this question, we performed a field experiment using tank bromeliads and their aquatic food web, composed of predatory damselfly larvae, macroinvertebrate prey and bacteria. We manipulated the presence and consumption ability of damselfly larvae under three rainfall scenarios (ambient, few large rainfall events and several small rainfall events), recorded the hydrological dynamics within bromeliads and examined the effects on macroinvertebrate colonization, nutrient cycling and bacterial biomass and turnover. Despite our large perturbations of rainfall, rainfall scenario had no effect on the hydrological dynamics of bromeliads. As a result, macroinvertebrate colonization and nutrient cycling depended on the hydrological stability of bromeliads, with no direct effect of rainfall or predation. In contrast, rainfall scenario determined the direction of the indirect effects of predators on bacteria, driven by both predator CEs and NCEs. These results suggest that rainfall and the hydrological stability of bromeliads had indirect effects on the food web through changes in the CEs and NCEs of predators. We suggest that future studies should consider the importance of the variability in hydrological dynamics among habitats as

  9. Structural and biochemical alterations of human diabetic dermis studied by 3H-lysine incorporation and microscopy

    International Nuclear Information System (INIS)

    Moczar, M.; Allard, R.; Ouzilou, J.; Robert, L.; Pieraggi, M.-T.; Bouissou, H.; Julian, M.

    1976-01-01

    The alteration of the structural organization of dermal connective tissue was studied by light and electron microscopy and by biochemical techniques in normal human and in diabetic patients using skin biopsies. Part of the tissue was used for light and electron microscopy, the rest was incubated in the presence of 3 H-lysine for four hours. The 3 H-lysine labelled biopsies were submitted to a sequential extraction procedure in order to obtain representative macromolecular fractions containing the matrix macromolecules. The extracts were analyzed for their chemical composition and radioactivity. Electron microscopy revealed microstructural modifications of the fibroblasts, of the collagen and elastic fibers in the diabetic dermis. The incorporation pattern of 3 H-lysine into the macromolecular fractions was different in the normal and diabetic skin biopsies. The percentage of total radioactivity incorporated increased significantly in the 1M CaCl 2 extractable fraction and in the 6M urea extractable fraction and decreased significantly in the collagenase and elastase extracts in diabetic skin biopsy. These results demonstrate the existence of morphological and biochemical alterations in diabetic connective tissue (dermis) reflecting alterations in the relative rates of synthesis and/or degradation of the intercellular matrix macromolecules as well as of their microarchitectural arrangement

  10. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners.

    Science.gov (United States)

    Fox, Kieran C R; Nijeboer, Savannah; Dixon, Matthew L; Floman, James L; Ellamil, Melissa; Rumak, Samuel P; Sedlmeier, Peter; Christoff, Kalina

    2014-06-01

    Numerous studies have begun to address how the brain's gray and white matter may be shaped by meditation. This research is yet to be integrated, however, and two fundamental questions remain: Is meditation associated with altered brain structure? If so, what is the magnitude of these differences? To address these questions, we reviewed and meta-analyzed 123 brain morphology differences from 21 neuroimaging studies examining ∼300 meditation practitioners. Anatomical likelihood estimation (ALE) meta-analysis found eight brain regions consistently altered in meditators, including areas key to meta-awareness (frontopolar cortex/BA 10), exteroceptive and interoceptive body awareness (sensory cortices and insula), memory consolidation and reconsolidation (hippocampus), self and emotion regulation (anterior and mid cingulate; orbitofrontal cortex), and intra- and interhemispheric communication (superior longitudinal fasciculus; corpus callosum). Effect size meta-analysis (calculating 132 effect sizes from 16 studies) suggests a global 'medium' effect size (Cohen's d¯=0.46; r¯=.19). Publication bias and methodological limitations are strong concerns, however. Further research using rigorous methods is required to definitively link meditation practice to altered brain morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.

    Directory of Open Access Journals (Sweden)

    Lili Li

    Full Text Available Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ mice. Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ mice. CREB(αΔ mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ. CREB(αΔ mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.

  12. Types of Pulmonary Hypertension

    Science.gov (United States)

    ... Home / Hypertension Pulmonary Hypertension What Is Pulmonary hypertension (PULL-mun-ary HI- ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  13. Living with Pulmonary Hypertension

    Science.gov (United States)

    ... Home / Hypertension Pulmonary Hypertension What Is Pulmonary hypertension (PULL-mun-ary HI- ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  14. Altered time structure of neuro-endocrine-immune system function in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Carughi Stefano

    2010-06-01

    TcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. Conclusion The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system

  15. Intracranial structural alteration predicts treatment outcome in patients with spontaneous intracranial hypotension.

    Science.gov (United States)

    Choi, Hanna; Lee, Mi Ji; Choi, Hyun Ah; Cha, Jihoon; Chung, Chin-Sang

    2018-02-01

    Background Intracranial structural dislocation in spontaneous intracranial hypotension (SIH) can be measured by various intracranial angles and distances. We aimed to identify the clinical significance of structural dislocation in relation to treatment outcome in patients with SIH. Methods In this retrospective analysis, we identified patients with SIH who received an epidural blood patch (EBP) at Samsung Medical Center from January 2005 to March 2015. Structural dislocation in pretreatment MRIs of SIH patients was assessed by measuring tonsillar herniation, mamillopontine distance, the angle between the vein of Galen and straight sinus (vG/SS angle), the pontomesencephalic angle, and the lateral ventricular angle. After the first EBP, poor response was defined as the persistence of symptoms that prompted a repeat EBP. Results Out of the 95 patients included, 31 (32.6%) showed poor response. Among the radiological markers of structural dislocation, the vG/SS angle was associated with poor response (49.82 ± 16.40° vs 66.58 ± 26.08°, p = 0.002). Among clinical variables, premorbid migraine ( p = 0.036) was related to poor response. In multivariate analysis, reduced vG/SS angle was independently associated with poor response (OR 1.04 [95% CI 1.01 - 1.07] per 1° decrease, p = 0.006). In 23 patients who underwent MRI after successful treatment, the vG/SS angle significantly increased after the EBP ( p < 0.001, by paired t-test), while two patients with aggravation or recurrence showed a further reduction of their vG/SS angles. Conclusions Intracranial structural dislocation, measured by the vG/SS angle, is associated with poor response to the first EBP in patients with SIH. Successful treatment can reverse the structural dislocation.

  16. Diseases of Pulmonary Surfactant Homeostasis

    Science.gov (United States)

    Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

    2015-01-01

    Advances in physiology and biochemistry have provided fundamental insights into the role of pulmonary surfactant in the pathogenesis and treatment of preterm infants with respiratory distress syndrome. Identification of the surfactant proteins, lipid transporters, and transcriptional networks regulating their expression has provided the tools and insights needed to discern the molecular and cellular processes regulating the production and function of pulmonary surfactant prior to and after birth. Mutations in genes regulating surfactant homeostasis have been associated with severe lung disease in neonates and older infants. Biophysical and transgenic mouse models have provided insight into the mechanisms underlying surfactant protein and alveolar homeostasis. These studies have provided the framework for understanding the structure and function of pulmonary surfactant, which has informed understanding of the pathogenesis of diverse pulmonary disorders previously considered idiopathic. This review considers the pulmonary surfactant system and the genetic causes of acute and chronic lung disease caused by disruption of alveolar homeostasis. PMID:25621661

  17. Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

    Science.gov (United States)

    Worbe, Yulia; Marrakchi-Kacem, Linda; Lecomte, Sophie; Valabregue, Romain; Poupon, Fabrice; Guevara, Pamela; Tucholka, Alan; Mangin, Jean-François; Vidailhet, Marie; Lehericy, Stephane; Hartmann, Andreas; Poupon, Cyril

    2015-02-01

    Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito

  18. Regional vulnerability of longitudinal cortical association connectivity: Associated with structural network topology alterations in preterm children with cerebral palsy.

    Science.gov (United States)

    Ceschin, Rafael; Lee, Vince K; Schmithorst, Vince; Panigrahy, Ashok

    2015-01-01

    alteration in eigenvector centrality, clustering coefficient (inter-regional) and participation co-efficient (inter-modular) alterations of frontal-striatal and fronto-limbic nodes suggesting re-organization of these pathways. Both along tract and structural topology network measurements correlated strongly with motor and visual clinical outcome scores. This study shows the value of combining along-tract analysis and structural network topology in depicting not only selective parietal occipital regional vulnerability but also reorganization of frontal-striatal and frontal-limbic pathways in preterm children with cerebral palsy. These finding also support the concept that widespread, but selective posterior-anterior neural network connectivity alterations in preterm children with cerebral palsy likely contribute to the pathogenesis of neurosensory and cognitive impairment in this group.

  19. Current density reversibly alters metabolic spatial structure of exoelectrogenic anode biofilms

    Science.gov (United States)

    Sun, Dan; Cheng, Shaoan; Zhang, Fang; Logan, Bruce E.

    2017-07-01

    Understanding how current densities affect electrogenic biofilm activity is important for wastewater treatment as current densities can substantially decrease at COD concentrations greater than those suitable for discharge to the environment. We examined the biofilm's response, in terms of viability and enzymatic activity, to different current densities using microbial electrolysis cells with a lower (0.7 V) or higher (0.9 V) added voltage to alter current production. Viability was assessed using florescent dyes, with dead cells identified on the basis of dye penetration due to a compromised cell outer-membrane (red), and live cells (intact membrane) fluorescing green. Biofilms operated with 0.7 V produced 2.4 ± 0.2 A m-2, and had an inactive layer near the electrode and a viable layer at the biofilm-solution interface. The lack of cell activity near the electrode surface was confirmed by using an additional dye that fluoresces only with enzymatic activity. Adding 0.9 V increased the current by 61%, and resulted in a single, more homogeneous and active biofilm layer. Switching biofilms between these two voltages produced outcomes associated with the new current rather than the previous biofilm conditions. These findings suggest that maintaining higher current densities will be needed to ensure long-term viability electrogenic biofilms.

  20. Non-dipper treated hypertensive patients do not have increased cardiac structural alterations

    Directory of Open Access Journals (Sweden)

    Magrini Fabio

    2003-02-01

    Full Text Available Abstract Background Non-dipping pattern in hypertensive patients has been shown to be associated with an excess of target organ damage and with an adverse outcome. The aim of our study was to assess whether a reduced nocturnal fall in blood pressure (BP, established on the basis of a single 24-h BP monitoring, in treated essential hypertensives is related to more prominent cardiac alterations. Methods We enrrolled 229 treated hypertensive patients attending the out-patient clinic of our hypertension centre; each patient was subjected to the following procedures : 1 clinic BP measurement; 2 blood and urine sampling for routine blood chemistry and urine examination; 3 standard 12-lead electrocardiogram; 4 echocardiography; 5 ambulatory BP monitoring (ABPM. For the purpose of this study ABPM was carried-out in three subgroups with different clinic BP profile : 1 patients with satisfactory BP control (BP 2 in men and 110 g/m2 in women, ≥51/gm2.7 in men and 47/g/m2.7 in women. Results Of the 229 study participants 119 (51.9% showed a fall in SBP/DBP Conclusions In treated essential hypertensives with or without BP control the extent of nocturnal BP decrease is not associated with an increase in LV mass or LVH prevalence; therefore, the non-dipping profile, diagnosed on the basis of a single ABPM, does not identify hypertensive patients with greater cardiac damage.

  1. Alteration of mammalian-cell toxicity of pesticides by structural iron(II) in ferruginous smectite.

    Science.gov (United States)

    Sorensen, Kara C; Stucki, Joseph W; Warner, Richard E; Plewa, Michael J

    2004-08-15

    The ultimate concern over pesticides in the environment is their toxic impact on nontarget organisms, including humans. Soil clays are known to interact with pesticides in ways that decrease the concentration of the parent compound in the soil solution (adsorption, sequestration, degradation). These phenomena are generally regarded as beneficial, but toxicological verification is lacking. In this study, mammalian-cell cytotoxicity of four commonly used agricultural chemicals (2,4-D, alachlor, dicamba, and oxamyl) was assessed after exposure to either reduced or oxidized ferruginous smectite (SWa-1). Results revealed that treatment with reduced smectite produced differential effects on mammalian-cell viability, depending on the pesticide. Oxamyl and alachlor reacted with reduced SWa-1 showed a significant decrease in their overall cytotoxic potential. Dicamba reacted with the reduced-clay treatment and generated products that were more toxic than the parent pesticide. Finally, no differences were observed between redox treatments for 2,4-D. The significance of these results is that oxidized smectites have virtually no influence on the toxicity of pesticides, whereas reduced-Fe smectite plays an important role in altering the cytotoxic potential of agricultural pesticides. The Fe oxidation state of clay minerals should, therefore, be taken into account in pesticide management programs.

  2. Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure

    DEFF Research Database (Denmark)

    Maccarana, Marco; Svensson, René B; Knutsson, Anki

    2017-01-01

    The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs' effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigat...

  3. Cassia alata alters Liver Structure in Rat | Amao | African Journal of ...

    African Journals Online (AJOL)

    Casia alata is a common plant in South West and its parts are freely used as herbs by the natives. Concomitantly, the prevalence of chronic liver disease is on the increase, thus the study was designed to investigate the effects of its crude extract on the rat liver structure. The methanolic extract of Cassia alata was ...

  4. Pulmonary Hypertension in Wild Type Mice and Animals with Genetic Deficit in KCa2.3 and KCa3.1 Channels

    DEFF Research Database (Denmark)

    Wandall-Frostholm, Christine; Skaarup, Lykke Moran; Sadda, Veeranjaneyulu

    2014-01-01

    mice with genetically encoded deficit of K(Ca)2.3 and K(Ca)3.1 channels, this study investigated the effect of loss of the channels in hypoxia-induced pulmonary hypertension. Approach and Result: Male wild type and K(Ca)3.1(-/-)/K(Ca)2.3(T/T(+DOX)) mice were exposed to chronic hypoxia for four weeks...... to induce pulmonary hypertension. The degree of pulmonary hypertension was evaluated by right ventricular pressure and assessment of right ventricular hypertrophy. Segments of pulmonary arteries were mounted in a wire myograph for functional studies and morphometric studies were performed on lung sections....... Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, increased lung weight, and increased hematocrit levels in either genotype. The K(Ca)3.1(-/-)/K(Ca)2.3(T/T(+DOX)) mice developed structural alterations in the heart with increased right ventricular wall thickness as well...

  5. Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

    Science.gov (United States)

    Davydyan, Garri

    2015-12-01

    The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what

  6. Alteration of Gills and Liver Histological Structure of Cyprinus carpio Exposed to Leachate

    Directory of Open Access Journals (Sweden)

    Tri Dewi Kusumaningrum Pribadi

    2017-07-01

    Full Text Available One of the main problems in the waste management in Indonesia is the treatment of leachate, which mostly dumped to the river This research is aimed to obtain information of histological alteration in gills and liver of C. carpio L. exposed to leachate. Measurements on the water quality parameters comprised water temperature, pH, and dissolved oxygen (DO. This research was conducted by exposing leachate to C. carpio for 96 hours. The concentration of leachate were 0 ppm, 80 ppm, and 100 ppm. Histological preparation were made on the gills and liver using 10% fixative Neutral Buffered Formalin and Ehrlich Hematoxylin-Eosin staining with qualitative observation descriptive analyses for discussion. The result showed that increasing water temperature is directly proportional to the leachate concentration in the aquaria, while the value of pH and DO inversely proportional to the leachate concentration. Damages on the gills with 80 ppm leachate concentrasion were identified as follows: fusion of secondary gill filaments and hyperplasia of epithelial cell, along with karyorrhexis and hydropic degeneration on the liver. Damages on the gills of fishes exposed to leachate with 100 ppm concentrasion were identified as follows: fusion of secondary gill filaments, hyperplasia of epithelial cell, congestion, and edema along with karyorrhexis, hydropic degeneration and melanomacrophage centre (MMC found on the liver. The results of this study can be used as an overview of the impact of an environmental pollution by leachate as indicated from histological damage to the gills and liver of C. carpio, thus contribute significan information to aquaculture sector and endorse better waste management

  7. The Latarjet coracoid process transfer procedure: alterations in the neurovascular structures.

    Science.gov (United States)

    Freehill, Michael T; Srikumaran, Umasuthan; Archer, Kristin R; McFarland, Edward G; Petersen, Steve A

    2013-05-01

    The Latarjet coracoid process transfer procedure is an established, reliable treatment for glenoid deficiency associated with recurrent anterior shoulder instability, but changes in neurovascular anatomy resulting from the procedure are a concern. The purpose of our cadaveric study was to identify changes in the neurovascular anatomy after a Latarjet procedure. We obtained 4 paired, fresh-frozen cadaveric forequarters (8 shoulders) from the Maryland State Anatomy Board. In each shoulder, we preoperatively measured the distances from the midanterior glenoid rim to the musculocutaneous nerve, axillary nerve, and axillary artery in 2 directions (lateral to medial and superior to inferior) and with the arm in 2 positions (0° abduction/neutral rotation; 30° abduction/30° external rotation), for a total of 12 measurements. We then created a standardized bony defect in the anterior-inferior glenoid, reconstructed it with the Latarjet procedure, and repeated the same measurements. Two examiners independently took each measurement twice. Inter-rater reliability was adequate, allowing pre-Latarjet measurements to be combined, averaged, and compared with combined and averaged post-Latarjet measurements by using paired Student t tests (significance, P ≤ .05). We found (1) significant differences in the location of the musculocutaneous nerve in the superior-to-inferior direction for both arm positions, (2) notably lax and consistently overlapping musculocutaneous and axillary nerves, and (3) an unchanged axillary artery location. The Latarjet procedure resulted in consistent and clinically significant alterations in the anatomic relationships of the musculocutaneous and axillary nerves, which may make them vulnerable to injury during revision surgery. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  8. Structural alteration of hexagonal birnessite by aqueous Mn(II): Impacts on Ni(II) sorption

    Energy Technology Data Exchange (ETDEWEB)

    Lefkowitz, Joshua P.; Elzinga, Evert J.

    2017-09-01

    We studied the impacts of aqueous Mn(II) (1 mM) on the sorption of Ni(II) (200 μM) by hexagonal birnessite (0.1 g L- 1) at pH 6.5 and 7.5 with batch experiments and XRD, ATR-FTIR and Ni K-edge EXAFS analyses. In the absence of Mn(II)aq, sorbed Ni(II) was coordinated predominantly as triple corner-sharing complexes at layer vacancies at both pH values. Introduction of Mn(II)aq into Ni(II)-birnessite suspensions at pH 6.5 caused Ni(II) desorption and led to the formation of edge-sharing Ni(II) complexes. This was attributed to competitive displacement of Ni(II) from layer vacancies by either Mn(II) or by Mn(III) formed through interfacial Mn(II)-Mn(IV) comproportionation, and/or incorporation of Ni(II) into the birnessite lattice promoted by Mn(II)-catalyzed recrystallization of the sorbent. Similar to Mn(II)aq, the presence of HEPES or MES caused the formation of edge-sharing Ni(II) sorption complexes in Ni(II)-birnessite suspensions, which was attributed to partial reduction of the sorbent by the buffers. At pH 7.5, interaction with aqueous Mn(II) caused reductive transformation of birnessite into secondary feitknechtite that incorporated Ni(II), enhancing removal of Ni(II) from solution. These results demonstrate that reductive alteration of phyllomanganates may significantly affect the speciation and solubility of Ni(II) in anoxic and suboxic environments.

  9. Structure alterations in Al-Y-based metallic glasses with La and Ni addition

    Science.gov (United States)

    Shi, X. M.; Wang, X. D.; Yu, Q.; Cao, Q. P.; Zhang, D. X.; Zhang, J.; Hu, T. D.; Lai, L. H.; Xie, H. L.; Xiao, T. Q.; Jiang, J. Z.

    2016-03-01

    The atomic structures of Al89Y11, Al90Y6.5La3.5, and Al82.8Y6.07Ni8La3.13 metallic glasses have been studied by using high energy X-ray diffraction, X-ray absorption fine structure combined with the ab initio molecular dynamics and reverse Monte Carlo simulations. It is demonstrated that the partial replacement of Y atoms by La has limited improvement of the glass forming ability (GFA), although La atoms reduce the ordering around Y atoms and also the fractions of icosahedron-like polyhedra centered by Al atoms. In contrast, Ni atoms can significantly improve the GFA, which are inclined to locate in the shell of polyhedra centered by Al, Y, and La atoms, mainly forming Ni-centered icosahedron-like polyhedra to enhance the spatial connectivity between clusters and suppress the crystallization.

  10. Pulmonary cryptococcosis.

    Science.gov (United States)

    McDonnell, J M; Hutchins, G M

    1985-02-01

    Observation of an unusual pulmonary distribution of cryptococci in a patient at autopsy prompted a review of 36 patients with pulmonary cryptococcosis listed in the autopsy files of The Johns Hopkins Hospital. The patients ranged in age from 2 to 89 years (mean, 49 years), 19 were female, and 18 were black. All but three patients had underlying debilitating diseases, and 23 patients had received steroids and/or chemotherapy. In 25 patients (69 per cent) cryptococcosis was a major factor contributing to death, through pulmonary disease in ten, systemic involvement in seven, and central nervous system disease in eight. In 15 patients (42 per cent) cryptococcosis was diagnosed clinically. Four basic morphologic patterns were observed: 1) Seven patients (19 per cent) had one or more peripheral pulmonary granulomas. In three of these patients the granulomas were apparently quiescent, and no other lesions were found. 2) Nineteen patients (53 per cent) had what has been called granulomatous pneumonia, with intra-alveolar proliferating organisms and varying degrees of inflammatory response, which, when present, ranged from acute inflammation to diffuse intra-alveolar granulomas with giant cells. 3) In seven patients (19 per cent) organisms were present diffusely within alveolar capillaries and interstitial tissues, and reactions ranged from little or no inflammation with numerous organisms to few organisms with miliary granulomas. 4) In three patients (8 per cent) both intra-alveolar and intravascular organisms were present in massive numbers, and the primary route of infection was uncertain. Fatalities from pulmonary and generalized infection occurred in patients in each histologic group. The results show marked variability both in pathologic reaction to cryptococci and in the clinical appreciation and significance of pulmonary cryptococcosis.

  11. Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

    Science.gov (United States)

    2014-01-31

    motif) ligand 7 TIMP metallopeptidase inhibitor I serpin peptidase inhibitor, clade A (alpha-I antiproteinase, antitrypsin). member 3 lipocalin 2...voltage-gated, type VII, alpha CD84 molecule ribonuclease T2 ubiquitin specific peptidase 18 fYN binding protein meiosis-specific nuclear structural I...containing 2 membrane-spanning 4-domains. subfamily A. member 6A receptor (chemosensory) transporter protein 4 CD180 molecule serpin peptidase

  12. Time-Varying Estimation of Crop Insurance Program in Altering North Dakota Farm Economic Structure

    OpenAIRE

    Coleman, Jane A.; Shaik, Saleem

    2009-01-01

    This study examines how federal farm policies, specifically crop insurance, have affected the farm economic structure of North Dakota’s agriculture sector. The system of derived input demand equations is estimated to quantify the changes in North Dakota farmers’ input use when they purchase crop insurance. Further, the cumulative rolling regression technique is applied to capture the varying effects of the farm policies over time. Empirical results from the system of input demand functions in...

  13. Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures

    DEFF Research Database (Denmark)

    Skinner, P J; Koshy, B T; Cummings, C J

    1997-01-01

    Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative disorders caused by an expansion of a polyglutamine tract. It is characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To understand the pathogenesis of SCA1, we examined the subcel......Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative disorders caused by an expansion of a polyglutamine tract. It is characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To understand the pathogenesis of SCA1, we examined.......5 microm across, whereas the expanded ataxin-1 localizes to a single approximately 2-microm structure, before the onset of ataxia. Mutant ataxin-1 localizes to a single nuclear structure in affected neurons of SCA1 patients. Similarly, COS-1 cells transfected with wild-type or mutant ataxin-1 show...... a similar pattern of nuclear localization; with expanded ataxin-1 occurring in larger structures that are fewer in number than those of normal ataxin-1. Colocalization studies show that mutant ataxin-1 causes a specific redistribution of the nuclear matrix-associated domain containing promyelocytic...

  14. [Sex difference of functional and structural alterations in the myocardium of rats with hypothyroidism].

    Science.gov (United States)

    Khara, M R; Pavlovych, S I; Mykhaĭliuk, V M

    2013-01-01

    In experiments on sexually mature rats we studied specific cholinergic regulations of the heart and the degree of its structural damage in hypothyroidism, depending on gender and hormone-productive activity of the gonads. Hypothyroidism in sexually mature males and females was modelled with mercazolil intragastric administration (75 mg/kg) daily during 15 days. We also studied the intensity of bradycardia, which occurred in response to electrical stimulation of vagus nerve and intravenous acetylcholine administration. The degree of structural heart damage was assessed by the percentage of damaged cardiomyocytes in the ventricles of myocardium. It was found that one of the mechanisms of bradycardia in merkazolil-induced hypothyroidism is an increase of the sensitivity of sinus node cholinergic receptors and release of more quanta of acetylcholine from stimulated nerves vagus endings, what was more intense in females. The intensity of bradycardia in hypothyroidism was more significant in gonadectomized animals than in individuals with preserved gonads. The mechanisms of its occurrence in males consist of release of greater amount of acetylcholine from the endings of the nerves vagus, and in females it was the result of significant increase of the sensitivity of sinus node cholinergic receptors. Regardless of the gonads activity, structural damage of the myocardium in merkazolil-induced hypothyroidism was more intensive in female rats.

  15. Structural brain alterations in hemifacial spasm: A voxel-based morphometry and diffusion tensor imaging study.

    Science.gov (United States)

    Tu, Ye; Yu, Tian; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

    2016-02-01

    Hemifacial spasm (HFS) is characterized by involuntary, irregular clonic or tonic movement of muscles innervated by the facial nerve. We evaluated structural reorganization in brain gray matter and white matter and whether neuroplasticity is linked to clinical features in HFS patients. High-resolution structural magnetic resonance imaging and diffusion tensor imaging data were acquired by 3.0 T MRI from 42 patients with HFS and 30 healthy subjects. The severity of the spasm was assessed according to Jankovic disability rating scale. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis were performed to identify regional grey matter volume (GMV) changes and whole-brain microstructural integrity disruption measured by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The VBM analysis showed that patients with HFS reduced GMV in the right inferior parietal lobule and increased GMV in the cerebellar lobule VIII, when compared with healthy subjects. Furthermore, within the HFS disease group, GMV decreased with the disease duration in the right inferior parietal lobule. TBSS did not identify group differences in diffusivity parameters. While no white matter integrity disruption was detected in the brain of patients with HFS, our study identified evident GMV changes in brain areas which were known to be involved in motor control. Our results suggest that HFS, a chronic neurovascular conflict disease, is related to structural reorganization in the brain. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Physical disturbance to ecological niches created by soil structure alters community composition of methanotrophs.

    Science.gov (United States)

    Kumaresan, Deepak; Stralis-Pavese, Nancy; Abell, Guy C J; Bodrossy, Levente; Murrell, J Colin

    2011-10-01

    Aggregates of different sizes and stability in soil create a composite of ecological niches differing in terms of physico-chemical and structural characteristics. The aim of this study was to identify, using DNA-SIP and mRNA-based microarray analysis, whether shifts in activity and community composition of methanotrophs occur when ecological niches created by soil structure are physically perturbed. Landfill cover soil was subject to three treatments termed: 'control' (minimal structural disruption), 'sieved' (sieved soil using 2 mm mesh) and 'ground' (grinding using mortar and pestle). 'Sieved' and 'ground' soil treatments exhibited higher methane oxidation potentials compared with the 'control' soil treatment. Analysis of the active community composition revealed an effect of physical disruption on active methanotrophs. Type I methanotrophs were the most active methanotrophs in 'sieved' and 'ground' soil treatments, whereas both Type I and Type II methanotrophs were active in the 'control' soil treatment. The result emphasize that changes to a particular ecological niche may not result in an immediate change to the active bacterial composition and change in composition will depend on the ability of the bacterial communities to respond to the perturbation. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  17. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

    Full Text Available Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH, the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

  18. Imaging of pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Van Dyck, P.; De Schepper, A.M.; Vanhoenacker, F.M.; Van den Brande, P.

    2003-01-01

    Tuberculosis, more than any other infectious disease, has always been a challenge, since it has been responsible for a great amount of morbidity and mortality in humans. After a steady decline in the number of new cases during the twentieth century, due to improved social and environmental conditions, early diagnosis, and the development of antituberculous medication, a stagnation and even an increase in the number of new cases was noted in the mid-1980s. The epidemiological alteration is multifactorial: global increase in developing countries; minority groups (HIV and other immunocompromised patients); and elderly patients due to an altered immune status. Other factors that may be responsible are a delayed diagnosis, especially in elderly patients, incomplete or inadequate therapy, and the emergence of multidrug-resistant tuberculosis. The course of the disease and its corresponding clinicoradiological pattern depends on the interaction between the organism and the host response. Classically, pulmonary tuberculosis has been classified in primary tuberculosis, which occurred previously in children, and postprimary tuberculosis, occurring in adult patients. In industrialized countries, however, there seems to be a shift of primary tuberculosis towards adults. Furthermore, due to an altered immunological response in certain groups, such as immunocompromised and elderly patients, an atypical radioclinical pattern may occur. The changing landscape, in which tuberculosis occurs, as well as the global resurgence, and the changed spectrum of the clinical and radiological presentation, justify a renewed interest of radiologists for the imaging features of pulmonary tuberculosis. This article deals with the usual imaging features of pulmonary tuberculosis as well as the atypical patterns encountered in immunodepressed and elderly patients. (orig.)

  19. Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study.

    Directory of Open Access Journals (Sweden)

    Sophia Mueller

    Full Text Available Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA. We applied diffusion tensor imaging (DTI, voxel-based morphometry (VBM and resting state functional connectivity magnetic resonance imaging (fcMRI to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male and 12 healthy controls (mean age 33.3, SD 9.0, 8 male. Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

  20. Collagen structural alterations contribute to stiffening of tissue after split-thickness skin grafting.

    Science.gov (United States)

    Rosin, Nicole L; Agabalyan, Natacha; Olsen, Katherine; Martufi, Giampaol; Gabriel, Vincent; Biernaskie, Jeff; Di Martino, Elena S

    2016-03-01

    The gold standard treatment for full thickness injuries of the skin is autologous split-thickness skin grafting. This involves harvesting the epidermis and superficial dermis from healthy skin and transplanting it onto the prepared wound bed. The donor site regenerates spontaneously, but the appendages and cellular components from the dermal layer are excluded from the graft. As a result, the new tissue is inferior; the healed graft site is dry/itchy, has decreased elasticity, increased fragility, and altered sensory function. Because this dermal layer is composed of collagen and other extracellular matrix proteins, the aim was to characterize the changes in the dermal collagen after split thickness grafting that could contribute to a deficit in functionality. This will serve as a baseline for future studies designed to improve skin function using pharmacological or cell-based therapies for skin repair. A xenograft model whereby human split-thickness grafts were implanted into full-thickness defects on immunocompromised (athymic Nu/Nu) mice was used. The grafts were harvested 4 and 8 weeks later. The collagen microstructure was assessed with second harmonic generation with dual-photon microscopy and light polarization analysis. Collagen fiber stiffness and engagement stretch were estimated by fitting the results of biaxial mechanical tensile tests to a histo-mechanical constitutive model. The stiffness of the collagen fibril-proteoglycan complex increased from 682 ± 226 kPa/sr to 1016 ± 324 kPa/sr between 4 and 8 weeks postgrafting. At the microstructural level there were significant decreases in both thickness of collagen fibers (3.60 ± 0.34 μm vs. 2.10 ± 0.27 μm) and waviness ratio (2.04 ± 0.17 vs. 1.43 ± 0.08) of the collagen fibers postgrafting. The decrease of the macroscopic engagement stretch from 1.19 ± 0.11 to 1.09 ± 0.08 over time postgrafting mirrored the decrease in waviness measured at the microscopic level

  1. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain.

    Science.gov (United States)

    Langevin, Helene M; Stevens-Tuttle, Debbie; Fox, James R; Badger, Gary J; Bouffard, Nicole A; Krag, Martin H; Wu, Junru; Henry, Sharon M

    2009-12-03

    Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP), there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. In each of 107 human subjects (60 with LBP and 47 without LBP), parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. There were no significant differences in age, sex, body mass index (BMI) or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had approximately 25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p<0.01 and p<0.001 respectively). This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

  2. Wheat and Rice Growth Stages and Fertilization Regimes Alter Soil Bacterial Community Structure, but Not Diversity

    Directory of Open Access Journals (Sweden)

    Jichen Wang

    2016-08-01

    Full Text Available Maintaining soil fertility and the microbial communities that determine fertility is critical to sustainable agricultural strategies, and the use of different organic fertilizer regimes represents an important practice in attempts to preserve soil quality. However, little is known about the dynamic response of bacterial communities to fertilization regimes across crop growth stages. In this study, we examined microbial community structure and diversity across eight representative growth stages of wheat-rice rotation under four different fertilization treatments: no nitrogen fertilizer (NNF, chemical fertilizer (CF, organic-inorganic mixed fertilizer (OIMF and organic fertilizer (OF. Quantitative PCR (QPCR and high-throughput sequencing of bacterial 16S rRNA gene fragments revealed that growth stage as the best predictor of bacterial community abundance and structure. Additionally, bacterial community compositions differed between wheat and rice rotations. Relative to soils under wheat rotation, soils under rice rotation contained higher relative abundances (RA of anaerobic and mesophilic microbes and lower RA of aerophilic microbes. With respect to fertilization regime, NNF plots had a higher abundance of nitrogen–fixing Cyanobacteria. OIMF had a lower abundance of ammonia-oxidizing Thaumarchaeota compared with CF. Application of chemical fertilizers (CF and OIMF treatments significantly increased the abundance of some generally oligotrophic bacteria such those belonging to the Acidobacteria, while more copiotrophic of the phylum Proteobacteria increased with organic fertilizer application. A high correlation coefficient was found when comparing RA of Acidobacteria based upon QPCR versus sequence analysis, yet poor correlations were found for the Alpha- and Beta- Proteobacteria, highlighting the caution required when interpreting these molecular data. In total, crop, fertilization scheme and plant developmental stage all influenced soil

  3. Effect of pulse electron beam characteristics on internal friction and structural alterations in epoxy

    Energy Technology Data Exchange (ETDEWEB)

    Zaikin, Yu.A. [Al Farabi Kazakh National University, Almaty (Kazakhstan)]. E-mail: drzaykin@mail.ru; Ismailova, G.A. [Al Farabi Kazakh National University, Almaty (Kazakhstan); Al-Sheikhly, M. [University of Maryland, College Park (United States)

    2007-08-15

    Temperature dependence of internal friction is experimentally studied in epoxy irradiated by 2.5 MeV pulse electron beam to different doses. Time dependence of internal friction characteristics associated with radiation-induced processes of polymer scission and cross-linking is analyzed and discussed. Experimental data on kinetics of structural transformations in epoxy are interpreted on the base of analytical solutions of differential equations for free radical accumulation during and after irradiation subject to the pulse irradiation mode and an arbitrary effective order of radical recombination.

  4. Cyanobacteria contain a structural homologue of the Hfq protein with altered RNA binding properties

    DEFF Research Database (Denmark)

    Bøggild, Andreas; Overgaard, Martin; Valentin-Hansen, Poul

    2009-01-01

    regulating mRNA turnover in eukaryotes. However, bacterial Hfq proteins are homohexameric, whereas eukaryotic Sm/Lsm proteins are heteroheptameric. Recently, Hfq proteins with poor sequence conservation were identified in archaea and cyanobacteria. In this article, we describe crystal structures of the Hfq...... proteins from the cyanobacteria Synechocystis sp. PCC 6803 and Anabaena PCC 7120 at 1.3 and 2.3 A resolution, respectively, and show that they retain the classic Sm fold despite low sequence conservation. In addition, the intersubunit contacts and RNA-binding site are divergent, and we show biochemically...

  5. Cyanobacteria contain a structural homologue of the Hfq protein with altered RNA-binding properties

    DEFF Research Database (Denmark)

    Bøggild, Andreas; Overgaard, Martin; Valentin-Hansen, Poul

    2009-01-01

    regulating mRNA turnover in eukaryotes. However, bacterial Hfq proteins are homohexameric, whereas eukaryotic Sm/Lsm proteins are heteroheptameric. Recently, Hfq proteins with poor sequence conservation were identified in archaea and cyanobacteria. In this article, we describe crystal structures of the Hfq...... proteins from the cyanobacteria Synechocystis sp. PCC 6803 and Anabaena PCC 7120 at 1.3 and 2.3 A resolution, respectively, and show that they retain the classic Sm fold despite low sequence conservation. In addition, the intersubunit contacts and RNA-binding site are divergent, and we show biochemically...

  6. Effect of pulse electron beam characteristics on internal friction and structural alterations in epoxy

    International Nuclear Information System (INIS)

    Zaikin, Yu.A.; Ismailova, G.A.; Al-Sheikhly, M.

    2007-01-01

    Temperature dependence of internal friction is experimentally studied in epoxy irradiated by 2.5 MeV pulse electron beam to different doses. Time dependence of internal friction characteristics associated with radiation-induced processes of polymer scission and cross-linking is analyzed and discussed. Experimental data on kinetics of structural transformations in epoxy are interpreted on the base of analytical solutions of differential equations for free radical accumulation during and after irradiation subject to the pulse irradiation mode and an arbitrary effective order of radical recombination

  7. Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    David eRoquis

    2014-07-01

    Full Text Available Schistosoma mansoni is a parasitic plathyhelminth responsible for intestinal schistosomiasis (or bilharziasis, a disease affecting 67 million people worldwide and causing an important economic burden. The schistosomicides hycanthone, and its later proxy oxamniquine, were widely used for treatments in endemic areas during the 20th century. Recently, the mechanism of action, as well as the genetic origin of a stably and Mendelian inherited resistance for both drugs was elucidated in two strains. However, several observations suggested early on that alternative mechanisms might exist, by which resistance could be induced for these two drugs in sensitive lines of schistosomes. This induced resistance appeared rapidly, within the first generation, but was metastable (not stably inherited. Epigenetic inheritance could explain such a phenomenon and we therefore re-analyzed the historical data with our current knowledge of epigenetics. In addition, we performed new experiments such as ChIP-seq on hycanthone treated worms. We found distinct chromatin structure changes between sensitive worms and induced resistant worms from the same strain. No specific pathway was discovered, but genes in which chromatin structure modification were observed are mostly associated with transport and catabolism, which makes sense in the context of the elimination of the drug. Specific differences were observed in the repetitive compartment of the genome. We finally describe what types of experiments are needed to understand the complexity of heritability that can be based on genetic and/or epigenetic mechanisms for drug resistance in schistosomes.

  8. Alcohol dehydrogenase, SDR and MDR structural stages, present update and altered era.

    Science.gov (United States)

    Jörnvall, Hans; Landreh, Michael; Östberg, Linus J

    2015-06-05

    It is now about half a century since molecular research on alcohol dehydrogenase (ADH), short-chain dehydrogenase/reductase (SDR) and medium-chain dehydrogenase/reductase (MDR) started. During this time, at least four stages of research can be distinguished, which led to many ADH, SDR and MDR structures from which their origins could be traced. An introductory summary of these stages is given, followed by a current update on the now known structures, including the present pattern of mammalian MDR-ADH enzymes into six classes and their evolutionary relationships. In spite of the wide spread in evolutionary changes from the "constant" class III to the more "variable" other classes, the change in class V (only confirmed as a transcript in humans) and class VI (absent in humans) are also restricted. Such spread in variability is visible also in other dehydrogenases, but not always so restricted in other co-evolving proteins we have studied. Finally, the shift in era of present ADH research is highlighted, as well as levels of likely future continuation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Structure alterations in Al-Y-based metallic glasses with La and Ni addition

    Energy Technology Data Exchange (ETDEWEB)

    Shi, X. M.; Wang, X. D., E-mail: wangxd@zju.edu.cn, E-mail: jiangjz@zju.edu.cn; Yu, Q.; Cao, Q. P.; Jiang, J. Z., E-mail: wangxd@zju.edu.cn, E-mail: jiangjz@zju.edu.cn [International Center for New-Structured Materials (ICNSM), Laboratory of New-Structured Materials, and School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Zhang, D. X. [State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027 (China); Zhang, J.; Hu, T. D. [Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing (China); Lai, L. H.; Xie, H. L.; Xiao, T. Q. [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201203 (China)

    2016-03-21

    The atomic structures of Al{sub 89}Y{sub 11}, Al{sub 90}Y{sub 6.5}La{sub 3.5}, and Al{sub 82.8}Y{sub 6.07}Ni{sub 8}La{sub 3.13} metallic glasses have been studied by using high energy X-ray diffraction, X-ray absorption fine structure combined with the ab initio molecular dynamics and reverse Monte Carlo simulations. It is demonstrated that the partial replacement of Y atoms by La has limited improvement of the glass forming ability (GFA), although La atoms reduce the ordering around Y atoms and also the fractions of icosahedron-like polyhedra centered by Al atoms. In contrast, Ni atoms can significantly improve the GFA, which are inclined to locate in the shell of polyhedra centered by Al, Y, and La atoms, mainly forming Ni-centered icosahedron-like polyhedra to enhance the spatial connectivity between clusters and suppress the crystallization.

  10. Altered Structural and Functional Connectivity of Juvenile Myoclonic Epilepsy: An fMRI Study

    Directory of Open Access Journals (Sweden)

    Chengqing Zhong

    2018-01-01

    Full Text Available The aim of this study was to investigate the structural and functional connectivity (FC of juvenile myoclonic epilepsy (JME using resting state functional magnetic resonance imaging (rs-fMRI. High-resolution T1-weighted magnetic resonance imaging (MRI and rs-fMRI data were collected in 25 patients with JME and in 24 control subjects. A FC analysis was subsequently performed, with seeding at the regions that demonstrated between-group differences in gray matter volume (GMV. Then, the observed structural and FCs were associated with the clinical manifestations. The decreased GMV regions were found in the bilateral anterior cerebellum, the right orbital superior frontal gyrus, the left middle temporal gyrus, the left putamen, the right hippocampus, the bilateral caudate, and the right thalamus. The changed FCs were mainly observed in the motor-related areas and the cognitive-related areas. The significant findings of this study revealed an important role for the cerebellum in motor control and cognitive regulation in JME patients, which also have an effect on the activity of the occipital lobe. In addition, the changed FCs were related to the clinical features of JME patients. The current observations may contribute to the understanding of the pathogenesis of JME.

  11. Perturbation of the Secondary Structure of the Scrapie Prion Protein Under Conditions that Alter Infectivity

    Science.gov (United States)

    Gasset, Maria; Baldwin, Michael A.; Fletterick, Robert J.; Prusiner, Stanley B.

    1993-01-01

    Limited proteolysis of the scrapie prion protein (PrPSc) generates PrP 27-30, which polymerizes into amyloid. By attenuated total reflection-Fourier transform infrared spectroscopy, PrP 27-30 polymers contained 54% β-sheet, 25% α-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. Almost 60% of the β-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. Decreased low-frequency β-sheet and increased turn content were found after SDS/PAGE, which disassembled the amyloid polymers, denatured PrP 27-30, and diminished scrapie infectivity. Acid-induced transitions were reversible, whereas alkali produced an irreversible transition centered at pH 10 under conditions that diminished infectivity. Whether PrPSc synthesis involves a transition in the secondary structure of one or more domains of the cellular prion protein from α-helical, random coil, or turn into β-sheet remains to be established.

  12. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    International Nuclear Information System (INIS)

    Haddad, Rami; Kasneci, Amanda; Mepham, Kathryn; Sebag, Igal A.

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  13. Structure alteration and immunological properties of {sup 60}Co gamma rays irradiated bothropstoxin-I

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Janaina A.; Yonamine, Camila Myiagui; Caproni, Priscila; Casare, Murilo; Spencer, Patrick Jack; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: janabap@gmail.com; Andrade Junior, Heitor Franco de; Vieira, Daniel Perez; Galisteo Junior, Andres Jimenez [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Instituto de Medicina Tropical de Sao Paulo, SP (Brazil). Lab. de Protozoologia

    2007-07-01

    About 20000 ophidic accidents are registered every year in Brazil. Serum therapy with equine antisera is the only efficient treatment. The venoms employed for immunization are fairly toxic and some venoms present low immunogenicity. Thus, the obtention of modified antigens with lower toxicity and preserved or improved immunogenicity would be useful. These toxins, when submitted to gamma radiation, in aqueous solution, present structural modifications. This occurs due to reactions with the radiolysis products of water. Some scavenger substances, such as NaNO{sub 3} and t-butanol, remove selectively the water radiolysis products. Ionizing radiation has proven to be a powerful tool to attenuate snake venoms toxicity without affecting and even increasing their immunogenic properties. However, the immune mechanisms involved in recognition, processing and presentation of irradiated antigens are yet unclear. In the present work, we investigated the immunological behavior of bothropstoxin-I (Bthx-1), before and after irradiation, in the presence of selective scavengers. Isogenic mice were immunized with either the native or the irradiated toxin, either with or without scavengers. After three immunizations, serum samples were collected and the antibody titers and isotypes were determined by Enzyme Linked Immuno Sorbent Assay. The antigenic characterization of native and irradiated bothropstoxin-I was performed by Western blot. The detection of expression of murine cytokines (IFN-{gamma} and IL-10) was analyzed by RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction). According to our data, irradiation process has promoted structural modifications in the toxin, characterized by higher molecular weight forms of the protein (aggregates and oligomers). Our data also indicate that irradiated toxins, alone or in the presence of NaNO{sub 3}, an aqueous electron scavenger, were immunogenic and the antibodies elicited by them were able to recognize the native toxin. On the other

  14. Microbial functional diversity alters the structure and sensitivity of oxygen deficient zones

    Science.gov (United States)

    Penn, Justin; Weber, Thomas; Deutsch, Curtis

    2016-09-01

    Oxygen deficient zones (ODZs) below the ocean surface regulate marine productivity by removing bioavailable nitrogen (N). A complex microbial community mediates N loss, but the interplay of its diverse metabolisms is poorly understood. We present an ecosystem model of the North Pacific ODZ that reproduces observed chemical distributions yet predicts different ODZ structure, rates, and climatic sensitivity compared to traditional geochemical models. An emergent lower O2 limit for aerobic nitrification lies below the upper O2 threshold for anaerobic denitrification, creating a zone of microbial coexistence that causes a larger ODZ but slower total rates of N loss. The O2-dependent competition for the intermediate nitrite produces gradients in its oxidation versus reduction, anammox versus heterotrophic denitrification, and the net ecological stoichiometry of N loss. The latter effect implies that an externally driven ODZ expansion should favor communities that more efficiently remove N, increasing the sensitivity of the N cycle to climate change.

  15. Zearalenone impairs the male reproductive system functions via inducing structural and functional alterations of sertoli cells.

    Science.gov (United States)

    Zheng, WangLong; Pan, ShunYe; Wang, Guangguang; Wang, Ya Jun; Liu, Qing; Gu, JianHong; Yuan, Yan; Liu, Xue Zhong; Liu, Zong Ping; Bian, Jian Chun

    2016-03-01

    The aim of this study was to investigate the effects of ZEA on the cytoskeletal structure, and factors specifically expressed by Sertoli cells. Primary Sertoli cells from rats aged 18-21 days were exposed to increasing ZEA concentrations (0, 5, 10, 20 μg mL(-1)) for 24 h. The results of immunofluorescence showed disruption of α-tubulin filaments and F-actin bundles, and damage to the nucleus of Sertoli cells on exposure to ZEA. In the control group, the protein level expression of androgen-binding protein (ABP), transferrin, vimentin, N-cadherin, and follicle-stimulating hormone receptor (FSHR) were decreased significantly (pfunctions of Sertoli cells, which may be an underlying cause of ZEA-induced reproductive toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Historical Population Structure of Central Valley Steelhead and Its Alteration by Dams

    Directory of Open Access Journals (Sweden)

    Steven T. Lindley

    2006-02-01

    Full Text Available Effective conservation and recovery planning for Central Valley steelhead requires an understanding of historical population structure. We describe the historical structure of the Central Valley steelhead evolutionarily significant unit using a multi-phase modeling approach. In the first phase, we identify stream reaches possibly suitable for steelhead spawning and rearing using a habitat model based on environmental envelopes (stream discharge, gradient, and temperature that takes a digital elevation model and climate data as inputs. We identified 151 patches of potentially suitable habitat with more than 10 km of stream habitat, with a total of 25,500 km of suitable habitat. We then measured the distances among habitat patches, and clustered together patches within 35 km of each other into 81 distinct habitat patches. Groups of fish using these 81 patches are hypothesized to be (or to have been independent populations for recovery planning purposes. Consideration of climate and elevation differences among the 81 habitat areas suggests that there are at least four major subdivisions within the Central Valley steelhead ESU that correspond to geographic regions defined by the Sacramento River basin, Suisun Bay area tributaries, San Joaquin tributaries draining the Sierra Nevada, and lower-elevation streams draining to the Buena Vista and Tulare basins, upstream of the San Joaquin River. Of these, it appears that the Sacramento River basin was the main source of steelhead production. Presently, impassable dams block access to 80% of historically available habitat, and block access to all historical spawning habitat for about 38% of the historical populations of steelhead.

  17. Large herbivores affect forest ecosystem functions by altering the structure of dung beetle communities

    Science.gov (United States)

    Iida, Taichi; Soga, Masashi; Koike, Shinsuke

    2018-04-01

    Dramatic increases in populations of large mammalian herbivores have become a major ecological issue, particularly in the northern hemisphere, due to their substantial impacts on both animal and plant communities through processes such as grazing, browsing, and trampling. However, little is known about the consequences of these population explosions on ecosystem functions. Here, we experimentally investigated how the population density of sika deer (Cervus nippon) in temperate deciduous forest areas in Japan affected the decomposition of mammal dung by dung beetles, which is a key process in forest ecosystems. We measured a range of environmental variables (e.g., vegetation cover, soil hardness) and the dung decomposition rate, measured as the amount of deer dung decomposed during one week, and sampled dung beetles at 16 study sites with three different deer densities (high/intermediate/low). We then used structural equation modeling to investigate the relationships between deer density, environmental variables, the biomass of dung beetles (classified into small or large species), and the dung decomposition rate. We found that the biomass of small species increased with increasing deer density, whereas that of large species was not related to deer density. Furthermore, the dung decomposition rate was positively related to the biomass of small species but unrelated to that of large species. Overall, our results showed that an increase in deer density affects the decomposition rate of mammal dung by changing the structure of dung beetle communities (i.e., increasing the number of small dung beetles). Such an understanding of how increases in large herbivore populations affect ecosystem functions is important for accurately evaluating the ecological consequences of their overabundance and ultimately managing their populations appropriately.

  18. Ligand and cation-induced structural alterations of the leukocyte integrin LFA-1.

    Science.gov (United States)

    Sen, Mehmet; Koksal, Adem C; Yuki, Koichi; Wang, Jianchuan; Springer, Timothy A

    2018-03-05

    In αI integrins including leukocyte function-associated antigen-1 (LFA-1), ligand-binding function is delegated to the αI domain, requiring extra steps in the relay of signals that activate ligand binding and coordinate it with cytoplasmic signals. Crystal structures reveal great variation in orientation between the αI domain and the remainder of the integrin head. Here, we investigated the mechanisms involved in signal relay to the αI domain, including whether binding of the ligand intercellular adhesion molecule-1 (ICAM-1) to the αI domain is linked to headpiece opening and engenders a preferred αI domain orientation. Using small-angle X-ray scattering (SAXS) and negative-stain EM we define structures of ICAM-1, LFA-1, and their complex, and the effect of activation by Mn 2+ Headpiece opening was substantially stabilized by substitution of Mg 2+ with Mn 2+ and became complete upon ICAM-1 addition. These agents stabilized αI-headpiece orientation, resulting in a well-defined orientation of ICAM-1 such that its tandem Ig-like domains pointed in the opposite direction from the β-subunit leg of LFA-1. Mutations in the integrin βI domain α1/α1` helix stabilizing either the open or the closed βI-domain conformation indicated that α1/α1` helix movements are linked to ICAM-1 binding by the αI domain and to the extended-open conformation of the ectodomain. The LFA-1--ICAM-1 orientation described here with ICAM-1 pointing anti-parallel to the LFA-1 β-subunit leg is the same orientation that would be stabilized by tensile force transmitted between the ligand and the actin cytoskeleton, and is consistent with the cytoskeletal force model of integrin activation. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Common hydraulic fracturing fluid additives alter the structure and function of anaerobic microbial communities

    Science.gov (United States)

    Mumford, Adam C.; Akob, Denise M.; Klinges, J. Grace; Cozzarelli, Isabelle M.

    2018-01-01

    The development of unconventional oil and gas (UOG) resources results in the production of large volumes of wastewater containing a complex mixture of hydraulic fracturing chemical additives and components from the formation. The release of these wastewaters into the environment poses potential risks that are poorly understood. Microbial communities in stream sediments form the base of the food chain and may serve as sentinels for changes in stream health. Iron-reducing organisms have been shown to play a role in the biodegradation of a wide range of organic compounds, and so to evaluate their response to UOG wastewater, we enriched anaerobic microbial communities from sediments collected upstream (background) and downstream (impacted) of an UOG wastewater injection disposal facility in the presence of hydraulic fracturing fluid (HFF) additives: guar gum, ethylene glycol, and two biocides, 2,2-dibromo-3-nitrilopropionamide (DBNPA) and bronopol (C3H6BrNO4). Iron reduction was significantly inhibited early in the incubations with the addition of biocides, whereas amendment with guar gum and ethylene glycol stimulated iron reduction relative to levels in the unamended controls. Changes in the microbial community structure were observed across all treatments, indicating the potential for even small amounts of UOG wastewater components to influence natural microbial processes. The microbial community structure differed between enrichments with background and impacted sediments, suggesting that impacted sediments may have been preconditioned by exposure to wastewater. These experiments demonstrated the potential for biocides to significantly decrease iron reduction rates immediately following a spill and demonstrated how microbial communities previously exposed to UOG wastewater may be more resilient to additional spills.

  20. A Longitudinal Assessment of Structural and Chemical Alterations in Mixed Martial Arts Fighters.

    Science.gov (United States)

    Mayer, Andrew R; Ling, Josef M; Dodd, Andrew B; Gasparovic, Charles; Klimaj, Stefan D; Meier, Timothy B

    2015-11-15

    Growing evidence suggests that temporally proximal acute concussions and repetitive subconcussive head injuries may lead to long-term neurological deficits. However, the underlying mechanisms of injury and their relative time-scales are not well documented in human injury models. The current study therefore investigated whether biomarkers of brain chemistry (magnetic resonance [MR] spectroscopy: N-acetylaspartate [NAA], combined glutamate and glutamine [Glx], total creatine [Cre], choline compounds [Cho], and myo-inositol [mI]) and structure (cortical thickness, white matter [WM]/subcortical volume) differed between mixed martial artists (MMA; n = 13) and matched healthy controls (HC) without a history of contact sport participation (HC; n = 14). A subset of participants (MMA = 9; HC = 10) returned for follow-up visits, with MMA (n = 3) with clinician-documented acute concussions also scanned serially. As expected, MMA self-reported a higher incidence of previous concussions and significantly more cognitive symptoms during prior concussion recovery. Fighters also exhibited reduced memory and processing speed relative to controls on neuropsychological testing coupled with cortical thinning in the left posterior cingulate gyrus and right occipital cortex at baseline assessment. Over a 1-year follow-up period, MMA experienced a significant decrease in both WM volume and NAA concentration, as well as relative thinning in the left middle and superior frontal gyri. These longitudinal changes did not correlate with self-reported metrics of injury (i.e., fight diary). In contrast, HC did not exhibit significant longitudinal changes over a 4-month follow-up period (p > 0.05). Collectively, current results provide preliminary evidence of progressive changes in brain chemistry and structure over a relatively short time period in individuals with high exposure to repetitive head hits. These findings require replication in independent samples.

  1. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

  2. Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

    Science.gov (United States)

    Koul, Ashwani; Bala, Shashi; Yasmeen; Arora, Neha

    2015-09-01

    This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. © 2014 Wiley Periodicals, Inc.

  3. Structural and functional alterations of two multidomain oxidoreductases induced by guanidine hydrochloride.

    Science.gov (United States)

    Jiao, Ming; Zhou, Yu-Ling; Li, Hong-Tao; Zhang, De-Ling; Chen, Jie; Liang, Yi

    2010-01-01

    The unfolding and refolding of two multidomain oxidoreductases, bovine liver catalase and flavoprotein bovine milk xanthine oxidase (XO), have been analyzed by fluorescence spectroscopy, circular dichroism, and activity measurements. Two intermediates, a partially folded active dimer disassembled from the native tetramer and a partially folded inactivated monomer, are found to exist in the conformational changes of catalase induced by guanidine hydrochloride (GdnHCl). Similarly, two intermediates, an active, compacted intermediate bound by flavin adenine dinucleotide (FAD) partially and an inactive flexible intermediate with FAD completely dissociated, exist in the conformational changes of XO induced by GdnHCl. The activity regains completely and an enhancement in activity compared with the native catalase or native XO is observed by dilution of catalase or XO incubated with GdnHCl at concentrations not >0.5 or 1.8 M into the refolding buffer, but the yield of reactivation for catalase or XO is zero when the concentration of GdnHCl is >1.5 or 3.0 M. The addition of FAD provides a remarkable protection against the inactivation of XO by GdnHCl under mild denaturing conditions, and the conformational change of XO is irreversible after FAD has been removed in the presence of a strong denaturing agent. These findings provide impetus for exploring the influences of cofactors such as FAD on the structure-function relationship of xanthine oxidoreductases.

  4. Altered structural correlates of impulsivity in adolescents with internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Xin eDu

    2016-01-01

    Full Text Available Recent studies suggested that internet gaming disorder (IGD was associated with impulsivity and structural abnormalities in brain gray matter. However, no morphometric study has examined the association between gray matter and impulsivity in IGD individuals. In this study, 25 adolescents with IGD and 27 healthy controls (HCs were recruited, and the relationship between Barratt impulsiveness scale-11 (BIS score and gray matter volume (GMV was investigated with the voxel-based morphometric (VBM correlation analysis. Then, the intergroup differences in correlation between BIS score and GMV were tested across all gray matter voxels. Our results showed that the correlations between BIS score and GMV of the right dorsomedial prefrontal cortex, the bilateral insula and the orbitofrontal cortex, the right amygdala and the left fusiform gyrus decreased in the IGD group compared to the HCs. Region-of-interest (ROI analysis revealed that GMV in all these clusters showed significant positive correlations with BIS score in the HCs, while no significant correlation was found in the IGD group. Our findings demonstrated that dysfunction of these brain areas involved in the behavior inhibition, attention and emotion regulation might contribute to impulse control problems in IGD adolescents.

  5. Ablation of mouse adult neurogenesis alters olfactory bulb structure and olfactory fear conditioning

    Directory of Open Access Journals (Sweden)

    Matthew Valley

    2009-11-01

    Full Text Available Adult neurogenesis replenishes olfactory bulb (OB interneurons throughout the life of most mammals, yet during this constant fl ux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the subventricular zone (SVZ. Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral defi cit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local fi eld potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB.

  6. Triclocarban Influences Antibiotic Resistance and Alters Anaerobic Digester Microbial Community Structure.

    Science.gov (United States)

    Carey, Daniel E; Zitomer, Daniel H; Hristova, Krassimira R; Kappell, Anthony D; McNamara, Patrick J

    2016-01-05

    Triclocarban (TCC) is one of the most abundant organic micropollutants detected in biosolids. Lab-scale anaerobic digesters were amended with TCC at concentrations ranging from the background concentration of seed biosolids (30 mg/kg) to toxic concentrations of 850 mg/kg to determine the effect on methane production, relative abundance of antibiotic resistance genes, and microbial community structure. Additionally, the TCC addition rate was varied to determine the impacts of acclimation time. At environmentally relevant TCC concentrations (max detect = 440 mg/kg), digesters maintained function. Digesters receiving 450 mg/kg of TCC maintained function under gradual TCC addition, but volatile fatty acid concentrations increased, pH decreased, and methane production ceased when immediately fed this concentration. The concentrations of the mexB gene (encoding for a multidrug efflux pump) were higher with all concentrations of TCC compared to a control, but higher TCC concentrations did not correlate with increased mexB abundance. The relative abundance of the gene tet(L) was greater in the digesters that no longer produced methane, and no effect on the relative abundance of the class 1 integron integrase encoding gene (intI1) was observed. Illumina sequencing revealed substantial community shifts in digesters that functionally failed from increased levels of TCC. More subtle, yet significant, community shifts were observed in digesters amended with TCC levels that did not inhibit function. This research demonstrates that TCC can select for a multidrug resistance encoding gene in mixed community anaerobic environments, and this selection occurs at concentrations (30 mg/kg) that can be found in full-scale anaerobic digesters (U.S. median concentration = 22 mg/kg, mean = 39 mg/kg).

  7. Modelos experimentais para avaliação das alterações pulmonares na síndrome hepatopulmonar Experimental models for assessment of pulmonary alterations in hepatopulmonary syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Vercelino

    2008-07-01

    Full Text Available OBJETIVO: O objetivo deste trabalho foi avaliar o melhor modelo experimental para observar alterações pulmonares que caracterizam a síndrome hepatopulmonar (SHP. MÉTODOS: Ratos machos Wistar, com peso médio de 250 g foram usados em quatro modelos experimentais: tetracloreto de carbono inalatório; tetracloreto de carbono intraperitoneal; ligadura parcial de veia porta; e ligadura de ducto biliar (LDB. Em todos os grupos os animais foram divididos em controle e experimental. Foram avaliadas as seguintes variáveis: transaminases; gasometria; lipoperoxidação por substâncias que reagem ao ácido tiobarbitúrico (TBARS e por quimiluminescência; e atividade antioxidante da enzima superóxido dismutase (SOD. Foi feito também o exame anatomopatológico do pulmão. RESULTADOS: Observou-se diferenças significativas entre os grupos LDB controle e experimental: aspartato amino transferase (105,3 ± 43 vs. 500,5 ± 90,3 UI/L; alanino aminotransferase (78,75 ± 37,7 vs. 162,75 ± 35,4 UI/L; fosfatase alcalina (160 ± 20,45 vs. 373,25 ± 45,44 UI/L; pressão parcial de oxigênio (85,25 ± 8,1 vs. 49,9 ± 22,5 mmHg; e saturação de hemoglobina (95 ± 0,7 vs. 73,3 ± 12,07%. A lipoperoxidação e a atividade antioxidante também demonstrou diferenças entre os dois grupos LDB (controle vs. experimental: TBARS (0,87 ± 0,3 vs. 2,01 ± 0,9 nmol/mg proteína; quimiluminescência (16008,41 ± 1171,45 vs. 20250,36 ± 827,82 cps/mg proteína; e SOD (6,66 ± 1,34 vs. 16,06 ± 2,67 UI/mg proteína. No exame anatomopatológico observou-se vasodilatação pulmonar no modelo de LDB. CONCLUSÕES: Os dados sugerem que o modelo de LDB pode ser usado para outros estudos envolvendo alterações hepáticas e suas relações com o estresse oxidativo e a SHP.OBJECTIVE: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS. METHODS: Male Wistar rats, with mean weight

  8. Development of computational algorithms for quantification of pulmonary structures; Desenvolvimento de algoritmos computacionais para quantificacao de estruturas pulmonares

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Marcela de; Alvarez, Matheus; Alves, Allan F.F.; Miranda, Jose R.A., E-mail: marceladeoliveira@ig.com.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Instituto de Biociencias. Departamento de Fisica e Biofisica; Pina, Diana R. [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Hospital das Clinicas. Departamento de Doencas Tropicais e Diagnostico por Imagem

    2012-12-15

    The high-resolution computed tomography has become the imaging diagnostic exam most commonly used for the evaluation of the squeals of Paracoccidioidomycosis. The subjective evaluations the radiological abnormalities found on HRCT images do not provide an accurate quantification. The computer-aided diagnosis systems produce a more objective assessment of the abnormal patterns found in HRCT images. Thus, this research proposes the development of algorithms in MATLAB® computing environment can quantify semi-automatically pathologies such as pulmonary fibrosis and emphysema. The algorithm consists in selecting a region of interest (ROI), and by the use of masks, filter densities and morphological operators, to obtain a quantification of the injured area to the area of a healthy lung. The proposed method was tested on ten HRCT scans of patients with confirmed PCM. The results of semi-automatic measurements were compared with subjective evaluations performed by a specialist in radiology, falling to a coincidence of 80% for emphysema and 58% for fibrosis. (author)

  9. Biochar affects soil organic matter cycling and microbial functions but does not alter microbial community structure in a paddy soil.

    Science.gov (United States)

    Tian, Jing; Wang, Jingyuan; Dippold, Michaela; Gao, Yang; Blagodatskaya, Evgenia; Kuzyakov, Yakov

    2016-06-15

    The application of biochar (BC) in conjunction with mineral fertilizers is one of the most promising management practices recommended to improve soil quality. However, the interactive mechanisms of BC and mineral fertilizer addition affecting microbial communities and functions associated with soil organic matter (SOM) cycling are poorly understood. We investigated the SOM in physical and chemical fractions, microbial community structure (using phospholipid fatty acid analysis, PLFA) and functions (by analyzing enzymes involved in C and N cycling and Biolog) in a 6-year field experiment with BC and NPK amendment. BC application increased total soil C and particulate organic C for 47.4-50.4% and 63.7-74.6%, respectively. The effects of BC on the microbial community and C-cycling enzymes were dependent on fertilization. Addition of BC alone did not change the microbial community compared with the control, but altered the microbial community structure in conjunction with NPK fertilization. SOM fractions accounted for 55% of the variance in the PLFA-related microbial community structure. The particulate organic N explained the largest variation in the microbial community structure. Microbial metabolic activity strongly increased after BC addition, particularly the utilization of amino acids and amines due to an increase in the activity of proteolytic (l-leucine aminopeptidase) enzymes. These results indicate that microorganisms start to mine N from the SOM to compensate for high C:N ratios after BC application, which consequently accelerate cycling of stable N. Concluding, BC in combination with NPK fertilizer application strongly affected microbial community composition and functions, which consequently influenced SOM cycling. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis.

    Science.gov (United States)

    Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John A; Lui, Su

    2018-03-01

    Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN

  11. Time-Dependent Confounding in the Study of the Effects of Regular Physical Activity in Chronic Obstructive Pulmonary Disease: An Application of the Marginal Structural Model

    DEFF Research Database (Denmark)

    Garcia-Aymerich, J.; Lange, P.; Serra, I.

    2008-01-01

    PURPOSE: Results from longitudinal studies about the association between physical activity and chronic obstructive pulmonary disease (COPD) may have been biased because they did not properly adjust for time-dependent confounders. Marginal structural models (MSMs) have been proposed to address...... this type of confounding. We sought to assess the presence of time-dependent confounding in the association between physical activity and COPD development and course by comparing risk estimates between standard statistical methods and MSMs. METHODS: By using the population-based cohort Copenhagen City Heart.......007) and in the MSM analysis (OR 0.79, p = 0.025). In the subgroup with COPD (n = 2,226), high physical activity was associated with a reduced risk of COPD admissions during follow-up (standard, incidence rate ratio, 0.74; p = 0.096; MSM, 0.68, p = 0.044), and with a reduced risk of mortality (standard, hazard ratio...

  12. Time-Dependent Confounding in the Study of the Effects of Regular Physical Activity in Chronic Obstructive Pulmonary Disease: An Application of the Marginal Structural Model

    DEFF Research Database (Denmark)

    Garcia-Aymerich, Judith; Lange, Peter; Serra, Ignasi

    2008-01-01

    Study, 6,568 subjects selected from the general population in 1976 were followed up until 2004 with three repeated examinations. RESULTS: Moderate to high compared with low physical activity was associated with a reduced risk of developing COPD both in the standard analysis (odds ratio [OR] 0.76, p = 0......PURPOSE: Results from longitudinal studies about the association between physical activity and chronic obstructive pulmonary disease (COPD) may have been biased because they did not properly adjust for time-dependent confounders. Marginal structural models (MSMs) have been proposed to address...... this type of confounding. We sought to assess the presence of time-dependent confounding in the association between physical activity and COPD development and course by comparing risk estimates between standard statistical methods and MSMs. METHODS: By using the population-based cohort Copenhagen City Heart...

  13. Pulmonary paracoccidioidomycosis.

    Science.gov (United States)

    Queiroz-Telles, Flavio; Escuissato, Dante L

    2011-12-01

    Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis, a soil saprophyte and thermally dimorphic fungus. The disease occurs mainly in rural workers in Latin America and is the most frequent endemic systemic mycosis in many countries of South America, where almost 10 million people are believed to be infected. Paracoccidioidomycosis should be regarded as a disease of travelers outside the endemic area. The primary pulmonary infection is subclinical in most cases, and individuals may remain infected throughout life without ever developing clinical signs. A small proportion of patients present with clinical disease. The lungs are frequently involved, and the pulmonary clinical manifestations must be differentiated from many other infectious and noninfectious conditions. Diagnosis should be based on epidemiological, clinical, and microbiological data. Effective treatment regimens are available to control the fungal infection, but most patients develop fibrotic sequelae that may severely hamper respiratory and adrenal function and the patient's well-being. © Thieme Medical Publishers.

  14. Pulmonary lymphangioleiomyomatosis

    International Nuclear Information System (INIS)

    Shawki, Hilal B.; Muhammad, Shakir M.; Reda, Amal N.; Abdulla, Thair S.; Ardalan, Delaram M.

    2007-01-01

    A 38-year-old Iraqi female, presented with one-year history of exertional dyspnea and exercise intolerance, without systemic or constitutional symptoms. Clinical examination revealed bilateral basal crackles with signs suggestive of left side pleural effusion, chest x-ray showed left sided pleural effusion, and diffuse bilateral basal pulmonary shadowing. Her biochemical analysis, hematological tests, electrocardiogram and echocardiography were normal, aspiration of the fluid revealed a chylothorax, the radiological shadowing was proved by computed tomography scan of the chest to be diffuse cystic lesions involving mostly lower lobes. Open lung biopsy showed dilated lymphatic vessels with surrounding inflammatory cells and smooth muscle fibers consistently with the diagnosis of pulmonary lymphangioleiomyomatosis. (author)

  15. Structural alterations in lateral prefrontal, parietal and posterior midline regions of men with chronic posttraumatic stress disorder.

    Science.gov (United States)

    Eckart, Cindy; Stoppel, Christian; Kaufmann, Jörn; Tempelmann, Claus; Hinrichs, Hermann; Elbert, Thomas; Heinze, Hans-Jochen; Kolassa, Iris-Tatjana

    2011-05-01

    So far, the neural network associated with posttraumatic stress disorder (PTSD) has been suggested to mainly involve the amygdala, hippocampus and medial prefrontal cortex. However, increasing evidence indicates that cortical regions extending beyond this network might also be implicated in the pathophysiology of PTSD. We aimed to investigate PTSD-related structural alterations in some of these regions. We enrolled highly traumatized refugees with and without (traumatized controls) PTSD and nontraumatized controls in the study. To increase the validity of our results, we combined an automatic cortical parcellation technique and voxel-based morphometry. In all, 39 refugees (20 with and 19 without PTSD) and 13 controls participated in the study. Participants were middle-aged men who were free of psychoactive substances and consumed little to no alcohol. Patients with PTSD (and to a lesser extent traumatized controls) showed reduced volumes in the right inferior parietal cortex, the left rostral middle frontal cortex, the bilateral lateral orbitofrontal cortex and the bilateral isthmus of the cingulate. An influence of cumulative traumatic stress on the isthmus of the cingulate and the lateral orbitofrontal cortex indicated that, at least in these regions, structural alterations might be associated with repeated stress experiences. Voxel-based morphometry analyses produced largely consistent results, but because of a poorer signal-to-noise ratio, conventional statistics did not reach significance. Although we controlled for several important confounding variables (e.g., sex, alcohol abuse) with our particular sample, this might limit the generalizibility of our data. Moreover, high comorbidity of PTSD and major depression hinders a definite separation of these conditions in our findings. Finally, the results concerning the lateral orbito frontal cortex should be interpreted with caution, as magnetic resonance imaging acquisition in this region is affected by a general

  16. The impact of an anti-gravity treadmill (AlterG) training on walking capacity and corticospinal tract structure in children with cerebral palsy.

    Science.gov (United States)

    Azizi, Sh; Marzbani, H; Raminfard, S; Birgani, P M; Rasooli, A H; Mirbagheri, M M

    2017-07-01

    We studied the effects of an anti-gravity treadmill (AlterG) training on walking capacity and corticospinal tract structure in children with Cerebral Palsy (CP). AlterG can help CP children walk on the treadmill by reducing their weights up to 80% and maintain their balance during locomotion. AlterG training thus has the potential to improve walking capacity permanently as it can provide systematic and intense locomotor training for sufficiently long period of time and produce brain neuroplasticity. AlterG training was given for 45 minutes, three times a week for two months. The neuroplasticity of corticospinal tract was evaluated using Diffusion Tensor Imaging (DTI). The fractional Anisotropy (FA) feature was extracted to quantify structural changes of the corticospinal tract. Walking capacity was evaluated using popular clinical measurements of gait; i.e., walking speed, mobility and balance. The evaluations were done before and after training. Our results revealed that AlterG training resulted in an increase in average FA value of the corticospinal tract following the training. The outcome measures of clinical assessments of gait presented enhanced walking capacity of the CP subjects. Our findings indicated that the improved walking capacity was concurrent with the enhancement of the corticospinal tract structure. The clinical implication is that AlterG training may be considered as a therapeutic tool for permanent gait improvement in CP children.

  17. Pulmonary Hypertension

    Science.gov (United States)

    Kim, John S.; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

    2015-01-01

    Objective Review the pharmacologic treatment options for pulmonary arterial hypertension (PAH) in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Data Sources and Study Selection Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of PAH therapies. Data Extraction Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Data Synthesis Specific targeted therapies developed for the treatment of adult patients with PAH have been applied for the benefit of children with PAH. With the exception of inhaled nitric oxide, there are no PAH medications approved for children in the US by the FDA. Unfortunately, data on treatment strategies in children with PAH are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for PAH in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with PAH. Prostacyclins provide adjunctive therapy for the treatment of PAH as infusions (intravenous and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first line vasodilator therapy in persistent pulmonary hypertension of the newborn, and is commonly used in the treatment of PAH in the Intensive Care Unit (ICU). Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with PAH. Soluble Guanylate Cyclase Stimulators are the first drug class to be FDA approved for the treatment of chronic thromboembolic pulmonary hypertension. Conclusions Literature and data supporting the

  18. Does Z' equal 1 or 2? Enhanced powder NMR crystallography verification of a disordered room temperature crystal structure of a p38 inhibitor for chronic obstructive pulmonary disease.

    Science.gov (United States)

    Widdifield, Cory M; Nilsson Lill, Sten O; Broo, Anders; Lindkvist, Maria; Pettersen, Anna; Svensk Ankarberg, Anna; Aldred, Peter; Schantz, Staffan; Emsley, Lyndon

    2017-06-28

    The crystal structure of the Form A polymorph of N-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-pyrazin-1-yl]benzamide (i.e., AZD7624), determined using single-crystal X-ray diffraction (scXRD) at 100 K, contains two molecules in the asymmetric unit (Z' = 2) and has regions of local static disorder. This substance has been in phase IIa drug development trials for the treatment of chronic obstructive pulmonary disease, a disease which affects over 300 million people and contributes to nearly 3 million deaths annually. While attempting to verify the crystal structure using nuclear magnetic resonance crystallography (NMRX), we measured 13 C solid-state NMR (SSNMR) spectra at 295 K that appeared consistent with Z' = 1 rather than Z' = 2. To understand this surprising observation, we used multinuclear SSNMR ( 1 H, 13 C, 15 N), gauge-including projector augmented-wave density functional theory (GIPAW DFT) calculations, crystal structure prediction (CSP), and powder XRD (pXRD) to determine the room temperature crystal structure. Due to the large size of AZD7624 (ca. 500 amu, 54 distinct 13 C environments for Z' = 2), static disorder at 100 K, and (as we show) dynamic disorder at ambient temperatures, NMR spectral assignment was a challenge. We introduce a method to enhance confidence in NMR assignments by comparing experimental 13 C isotropic chemical shifts against site-specific DFT-calculated shift distributions established using CSP-generated crystal structures. The assignment and room temperature NMRX structure determination process also included measurements of 13 C shift tensors and the observation of residual dipolar coupling between 13 C and 14 N. CSP generated ca. 90 reasonable candidate structures (Z' = 1 and Z' = 2), which when coupled with GIPAW DFT results, room temperature pXRD, and the assigned SSNMR data, establish Z' = 2 at room temperature. We find that the polymorphic Form A of AZD7624 is maintained at

  19. Facts about Pulmonary Atresia

    Science.gov (United States)

    ... Websites Information For… Media Policy Makers Facts about Pulmonary Atresia Recommend on Facebook Tweet Share Compartir Click ... pick up oxygen for the body. What is Pulmonary Atresia? Pulmonary atresia is a birth defect of ...

  20. Pulmonary manifestations of malaria

    Energy Technology Data Exchange (ETDEWEB)

    Rauber, K.; Enkerlin, H.L.; Riemann, H.; Schoeppe, W.

    1987-05-01

    We report on the two different types of pulmonary manifestations in acute plasmodium falciparum malaria. The more severe variant shows long standing interstitial pulmonary infiltrates, whereas in the more benign courses only short-term pulmonary edemas are visible.

  1. Reactive species and pulmonary edema.

    Science.gov (United States)

    Iles, Karen E; Song, Weifeng; Miller, David W; Dickinson, Dale A; Matalon, Sadis

    2009-10-01

    Pulmonary edema occurs when fluid flux into the lung interstitium exceeds its removal, resulting in hypoxemia and even death. Noncardiogenic pulmonary edema (NPE) generally results when microvascular and alveolar permeability to plasma proteins increase, one possible etiology being oxidant injury. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Experimental systems in which either RONS are increased or protective antioxidant mechanisms are decreased result in alterations of epithelial sodium channel activity and support the hypothesis that RONS are important in NPE. Both basic and clinical studies are needed to critically define the RONS-NPE connection and the capacity of antioxidant therapy (either alone or as a supplement to β-agonists) to improve patient outcome.

  2. Acidic pH triggers conformational changes at the NH2-terminal propeptide of the precursor of pulmonary surfactant protein B to form a coiled coil structure.

    Science.gov (United States)

    Bañares-Hidalgo, A; Pérez-Gil, J; Estrada, P

    2014-07-01

    Pulmonary surfactant protein SP-B is synthesized as a larger precursor, proSP-B. We report that a recombinant form of human SP-BN forms a coiled coil structure at acidic pH. The protonation of a residue with pK=4.8±0.06 is the responsible of conformational changes detected by circular dichroism and intrinsic fluorescence emission. Sedimentation velocity analysis showed protein oligomerisation at any pH condition, with an enrichment of the species compatible with a tetramer at acidic pH. Low 2,2,2,-trifluoroethanol concentration promoted β-sheet structures in SP-BN, which bind Thioflavin T, at acidic pH, whereas it promoted coiled coil structures at neutral pH. The amino acid stretch predicted to form β-sheet parallel association in SP-BN overlaps with the sequence predicted by several programs to form coiled coil structure. A synthetic peptide ((60)W-E(85)) designed from the sequence of the amino acid stretch of SP-BN predicted to form coiled coil structure showed random coil conformation at neutral pH but concentration-dependent helical structure at acidic pH. Sedimentation velocity analysis of the peptide indicated monomeric state at neutral pH (s20, w=0.55S; Mr~3kDa) and peptide association (s20, w=1.735S; Mr=~14kDa) at acidic pH, with sedimentation equilibrium fitting to a Monomer-Nmer-Mmer model with N=6 and M=4 (Mr=14692Da). We propose that protein oligomerisation through coiled-coil motifs could then be a general feature in the assembly of functional units in saposin-like proteins in general and in the organization of SP-B in a functional surfactant, in particular. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Solitary pulmonary nodule

    Science.gov (United States)

    Lung cancer - solitary nodule; Infectious granuloma - pulmonary nodule; SPN ... More than half of all solitary pulmonary nodules are noncancerous ... infections. Infectious granulomas (which are formed by cells as ...

  4. Pulmonary arterial hypertension : an update

    NARCIS (Netherlands)

    Hoendermis, E. S.

    2011-01-01

    Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance

  5. A histological study of the effect of exogenous melatonin on gentamicin induced structural alterations of proximal tubules in rats.

    Science.gov (United States)

    Kapić, Dina; Mornjaković, Zakira; Ćosović, Esad; Šahinović, Maida

    2014-02-01

    The aim of this research was to assess the reactive changes of rat proximal tubules caused by gentamicin and the effect of relatively low doses of melatonin. 48 adult male Wistar rats were distributed into six groups of equal size which all received one of the following daily intraperitoneal injections: vehicle (5% ethanol in Ringer solution) during 11 days (C); gentamicin (80 mg/kg) during 8 days (G), two groups which concomitantly received gentamicin (80 mg/kg) during 8 days and melatonin in two different test doses (5 or 20 mg/kg) during 11 days (GM1, GM2) and two groups treated only with melatonin in two different doses (5 or 20 mg/kg) during 11 days (M1, M2). Histological analysis included qualitative and semi-quantitative light microscopy analysis of proximal tubules. Exogenous melatonin had no significant effect on the microstructure, independently of dosis. The changes of proximal tubules microstructure induced by gentamicin were expressed in the form of granulovacuolar degeneration, necrosis and desquamation. The grade of proximal tubular changes was smaller in animals who besides gentamicin received melatonin. Melatonin has a dose dependent protective effect on the structural alterations of proximal tubules of the kidney induced by gentamicin.

  6. Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture.

    Science.gov (United States)

    Minkwitz, Susann; Schmock, Aysha; Kurtoglu, Alper; Tsitsilonis, Serafeim; Manegold, Sebastian; Wildemann, Britt; Klatte-Schulz, Franka

    2017-10-20

    A balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) is required to maintain tendon homeostasis. Variation in this balance over time might impact on the success of tendon healing. This study aimed to analyze structural changes and the expression profile of MMPs and TIMPs in human Achilles tendons at different time-points after rupture. Biopsies from 37 patients with acute Achilles tendon rupture were taken at surgery and grouped according to time after rupture: early (2-4 days), middle (5-6 days), and late (≥7 days), and intact Achilles tendons served as control. The histological score increased from the early to the late time-point after rupture, indicating the progression towards a more degenerative status. In comparison to intact tendons, qRT-PCR analysis revealed a significantly increased expression of MMP-1, -2, -13, TIMP-1, COL1A1, and COL3A1 in ruptured tendons, whereas TIMP-3 decreased. Comparing the changes over time post rupture, the expression of MMP-9, -13, and COL1A1 significantly increased, whereas MMP-3 and -10 expression decreased. TIMP expression was not significantly altered over time. MMP staining by immunohistochemistry was positive in the ruptured tendons exemplarily analyzed from early and late time-points. The study demonstrates a pivotal contribution of all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the early human tendon healing process.

  7. Low concentrations, potential ecological consequences: Synthetic estrogens alter life-history and demographic structures of aquatic invertebrates

    International Nuclear Information System (INIS)

    Souza, María Sol; Hallgren, Per; Balseiro, Esteban; Hansson, Lars-Anders

    2013-01-01

    Contraceptive drugs are nowadays found in aquatic environments around the globe. Particularly, 17α-ethinylestradiol (EE 2 ) may act even at low concentrations, such as those recorded in natural ecosystems. We evaluated the physiological effects of EE 2 on cyclopoids and calanoids, common copepods in both marine and freshwater communities. We used three EE 2 concentrations and assessed its impact on activity of different physiological endpoints: Acetylcholinesterase (neurotransmission), Glutathione S-transferase (detoxifying system), and Caspase-3 (apoptosis). While EE 2 exerts, distinctive effect on detoxifying and apoptotic systems, no effect on AChE was observed at environmental doses. Our results show that EE 2 exposure affects differently copepod physiology endpoints, altering moulting process, adult recruitment in calanoids and calanoid to cyclopoid ratio. The ecological consequences of this underlying physiological process may affect since life history to population and community structures, and this represent a new aspects of this xenobiotic in natural systems. Highlights: •We evaluated physiological effects of 17α-ethinylestradiol (EE 2 ) on copepods. •We measured the EE 2 effect on neurotransmission, detoxifying system and apoptosis. •EE 2 exert distinctive effect on detoxifying and apoptotic systems. •EE 2 affects differently calanoids and cyclopoids moulting and adult recruitment. •Physiological impact in invertebrates' communities is a novel aspect of EE 2 effects. -- Anthropogenic estrogens modify the physiological functioning of aquatic invertebrates

  8. Enhanced Bio-hydrogen Production from Protein Wastewater by Altering Protein Structure and Amino Acids Acidification Type

    Science.gov (United States)

    Xiao, Naidong; Chen, Yinguang; Chen, Aihui; Feng, Leiyu

    2014-01-01

    Enhanced bio-hydrogen production from protein wastewater by altering protein structure and amino acids acidification type via pH control was investigated. The hydrogen production reached 205.2 mL/g-protein when protein wastewater was pretreated at pH 12 and then fermented at pH 10. The mechanism studies showed that pH 12 pretreatment significantly enhanced protein bio-hydrolysis during the subsequent fermentation stage as it caused the unfolding of protein, damaged the protein hydrogen bonding networks, and destroyed the disulfide bridges, which increased the susceptibility of protein to protease. Moreover, pH 10 fermentation produced more acetic but less propionic acid during the anaerobic fermentation of amino acids, which was consistent with the theory of fermentation type affecting hydrogen production. Further analyses of the critical enzymes, genes, and microorganisms indicated that the activity and abundance of hydrogen producing bacteria in the pH 10 fermentation reactor were greater than those in the control. PMID:24495932

  9. Mercury alters the bacterial community structure and diversity in soil even at concentrations lower than the guideline values.

    Science.gov (United States)

    Mahbub, Khandaker Rayhan; Subashchandrabose, Suresh Ramraj; Krishnan, Kannan; Naidu, Ravi; Megharaj, Mallavarapu

    2017-03-01

    This study evaluated the effect of inorganic mercury (Hg) on bacterial community and diversity in different soils. Three soils-neutral, alkaline and acidic-were spiked with six different concentrations of Hg ranging from 0 to 200 mg kg -1 and aged for 90 days. At the end of the ageing period, 18 samples from three different soils were investigated for bacterial community structure and soil physicochemical properties. Illumina MiSeq-based 16s ribosomal RNA (rRNA) amplicon sequencing revealed the alteration in the bacterial community between un-spiked control soils and Hg-spiked soils. Among the bacterial groups, Actinobacteria (22.65%) were the most abundant phyla in all samples followed by Proteobacteria (21.95%), Bacteroidetes (4.15%), Firmicutes (2.9%) and Acidobacteria (2.04%). However, the largest group showing increased abundance with higher Hg doses was the unclassified group (45.86%), followed by Proteobacteria. Mercury had a considerable negative impact on key soil functional bacteria such as ammonium oxidizers and nitrifiers. Canonical correspondence analysis (CCA) indicated that among the measured soil properties, Hg had a major influence on bacterial community structure. Furthermore, nonlinear regression analysis confirmed that Hg significantly decreased soil bacterial alpha diversity in lower organic carbon containing neutral and alkaline soils, whereas in acidic soil with higher organic carbon there was no significant correlation. EC 20 values obtained by a nonlinear regression analysis indicated that Hg significantly decreased soil bacterial diversity in concentrations lower than several guideline values.

  10. Solution-active structural alterations in liganded hemoglobins C (beta6 Glu --> Lys) and S (beta6 Glu --> Val).

    Science.gov (United States)

    Hirsch, R E; Juszczak, L J; Fataliev, N A; Friedman, J M; Nagel, R L

    1999-05-14

    Based upon existing crystallographic evidence, HbS, HbC, and HbA have essentially the same molecular structure. However, important areas of the molecule are not well defined crystallographically (e.g. the N-terminal nonhelical portion of the alpha and beta chains), and conformational constraints differ in solution and in the crystalline state. Over the years, our laboratory and others have provided evidence of conformational changes in HbS and, more recently, in HbC. We now present data based upon allosteric perturbation monitored by front-face fluorescence, ultraviolet resonance Raman spectroscopy, circular dichroism, and oxygen equilibrium studies that confirm and significantly expand previous findings suggesting solution-active structural differences in liganded forms of HbS and HbC distal to the site of mutation and involving the 2,3-diphosphoglycerate binding pocket. The liganded forms of these hemoglobins are of significant interest because HbC crystallizes in the erythrocyte in the oxy form, and oxy HbS exhibits increased mechanical precipitability and a high propensity to oxidize. Specific findings are as follows: 1) differences in the intrinsic fluorescence indicate that the Trp microenvironments are more hydrophobic for HbS > HbC > HbA, 2) ultraviolet resonance Raman spectroscopy detects alterations in Tyr hydrogen bonding, in Trp hydrophobicity at the alpha1beta2 interface (beta37), and in the A-helix (alpha14/beta15) of both chains, 3) displacement by inositol hexaphosphate of the Hb-bound 8-hydroxy-1,3,6-pyrenetrisulfonate (the fluorescent 2,3-diphosphoglycerate analog) follows the order HbA > HbS > HbC, and 4) oxygen equilibria measurements indicate a differential allosteric effect by inositol hexaphosphate for HbC approximately HbS > HbA.

  11. Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups.

    Science.gov (United States)

    Gien, Jason; Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H

    2016-12-01

    Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ET A (BQ123/BQ610) and ET B (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1-ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. Copyright © 2016 the American Physiological Society.

  12. Natural acidification changes the timing and rate of succession, alters community structure, and increases homogeneity in marine biofouling communities.

    Science.gov (United States)

    Brown, Norah E M; Milazzo, Marco; Rastrick, Samuel P S; Hall-Spencer, Jason M; Therriault, Thomas W; Harley, Christopher D G

    2018-01-01

    Ocean acidification may have far-reaching consequences for marine community and ecosystem dynamics, but its full impacts remain poorly understood due to the difficulty of manipulating pCO 2 at the ecosystem level to mimic realistic fluctuations that occur on a number of different timescales. It is especially unclear how quickly communities at various stages of development respond to intermediate-scale pCO 2 change and, if high pCO 2 is relieved mid-succession, whether past acidification effects persist, are reversed by alleviation of pCO 2 stress, or are worsened by departures from prior high pCO 2 conditions to which organisms had acclimatized. Here, we used reciprocal transplant experiments along a shallow water volcanic pCO 2 gradient to assess the importance of the timing and duration of high pCO 2 exposure (i.e., discrete events at different stages of successional development vs. continuous exposure) on patterns of colonization and succession in a benthic fouling community. We show that succession at the acidified site was initially delayed (less community change by 8 weeks) but then caught up over the next 4 weeks. These changes in succession led to homogenization of communities maintained in or transplanted to acidified conditions, and altered community structure in ways that reflected both short- and longer-term acidification history. These community shifts are likely a result of interspecific variability in response to increased pCO 2 and changes in species interactions. High pCO 2 altered biofilm development, allowing serpulids to do best at the acidified site by the end of the experiment, although early (pretransplant) negative effects of pCO 2 on recruitment of these worms were still detectable. The ascidians Diplosoma sp. and Botryllus sp. settled later and were more tolerant to acidification. Overall, transient and persistent acidification-driven changes in the biofouling community, via both past and more recent exposure, could have important

  13. [Idiopathic pulmonary hemosiderosis with dendriform pulmonary ossification].

    Science.gov (United States)

    Barrera, Ana Madeleine; Vargas, Leslie

    2016-12-01

    Pulmonary ossification is a rare and usually asymptomatic finding reported as incidental in lung biopsies. Similarly, idiopathic pulmonary hemosiderosis is a rare cause of pulmonary infiltrates. We report the case of a 64-year old man with chronic respiratory symptoms in whom these two histopathological findings converged.

  14. Structural Alterations of Segmented Macular Inner Layers in Aquaporin4-Antibody-Positive Optic Neuritis Patients in a Chinese Population.

    Directory of Open Access Journals (Sweden)

    Chunxia Peng

    Full Text Available This study aimed to analyse the structural injury of the peripapillary retinal nerve fibre layer (pRNFL and segmented macular layers in optic neuritis (ON in aquaporin4-antibody (AQP4-Ab seropositivity(AQP4-Ab-positiveON patients and in AQP4-Ab seronegativity (AQP4-Ab-negative ON patients in order to evaluate their correlations with the best-corrected visual acuity (BCVA and the value of the early diagnosis of neuromyelitis optica (NMO.This is a retrospective, cross-sectional and control observational study.In total, 213 ON patients (291 eyes and 50 healthy controls (HC (100 eyes were recruited in this study. According to a serum AQP4-Ab assay, 98 ON patients (132 eyes were grouped as AQP4-Ab-positive ON and 115 ON patients (159 eyes were grouped as AQP4-Ab-negative ON cohorts. All subjects underwent scanning with spectralis optical coherence tomography (OCT and BCVA tests. pRNFL and segmented macular layer measurements were analysed.The pRNFL thickness in AQP4-Ab-positive ON eyes showed a more serious loss during 0-2 months (-27.61μm versus -14.47 μm and ≥6 months (-57.91μm versus -47.19μm when compared with AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON preferentially damaged the nasal lateral pRNFL. The alterations in the macular ganglion cell layer plus the inner plexiform layer (GCIP in AQP4-Ab-positive ON eyes were similar to those in AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON eyes had entirely different injury patterns in the inner nuclear layer (INL compared with AQP4-Ab-negative ON eyes during the first 6 months after the initial ON attack. These differences were as follows: the INL volume of AQP4-Ab-positive ON eyes had a gradual growing trend compared with AQP4-Ab-negative ON eyes, and it increased rapidly during 0-2 months, reached its peak during 2-4 months, and then decreased gradually. The pRNFL and GCIP in AQP4-Ab-positive ON eyes had positive correlations with BCVA. When the pRNFL thickness decreased to 95%CI (50.77

  15. Alteraciones estructurales de la glándula tiroidea tras la radioterapia Structural alterations of thyroid gland after radiotherapy

    Directory of Open Access Journals (Sweden)

    Caridad Verdecia Cañizares

    2009-03-01

    present paper was to report cased detected in our study of structural anomalies of thyroid gland in patients underwent radiotherapy for treatment of malignant head and neck tumors. METHODS: A cross-sectional and descriptive study was carried out to determine prevalence of structural alterations of thyroid gland in 43 patients survival of head-neck tumors underwent radiotherapy admitted in "William Soler" and "Juan Manual Márquez" Teaching Hospitals during 10 years (1990 to 2000. RESULTS: More frequent structural alteration of thyroid gland includes glandular fibrosis (18,5% followed by thyroid carcinoma, and of simple cysts of that gland (11,1% respectively. There were 2 cases of differential carcinoma of thyroid gland (7, 4%, and one of adeno-follicular mixed injury (3, 7%. Fine-needle aspirate cytology allows detection of most of these injuries and also the intra-parenchymatous guided-echography of this gland. Treatment of injuries founded was surgical and we performed a total thyroidectomy in two patients presenting with differential carcinoma of thyroid gland, subtotal thyroidectomy in t here patients with cysts of that gland, and thyroid adenomas. In cases of glandular fibrosis there was a concomitant thyroid hypofunction, thus, we administered substitute treatment using Levothyroxine. CONCLUSIONS: Fine-needle aspiration cytology by means of echography of thyroid gland allows diagnosing of structural alterations no detected in physical examination. More irradiated malignant pathology was non-Hodgkin lymphomas. More doses of irradiation, more is thyroid pathology.

  16. Perfusion defects in pulmonary perfusion iodine maps: causes and semiology.

    Science.gov (United States)

    Bustos Fiore, A; González Vázquez, M; Trinidad López, C; Mera Fernández, D; Costas Álvarez, M

    2017-12-14

    to describe the usefulness of dual-energy CT for obtaining pulmonary perfusion maps to provide morphological and functional information in patients with pulmonary embolisms. To review the semiology of perfusion defects due to pulmonary embolism so they can be differentiated from perfusion defects due to other causes: alterations outside the range used in the iodine map caused by other diseases of the lung parenchyma or artifacts. CT angiography of the pulmonary arteries is the technique of choice for the diagnosis of pulmonary embolisms. New dual-energy CT scanners are useful for detecting perfusion defects secondary to complete or partial obstruction of pulmonary arteries and is most useful for detecting pulmonary embolisms in subsegmental branches. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Acrolein - a pulmonary hazard.

    Science.gov (United States)

    Bein, Kiflai; Leikauf, George D

    2011-09-01

    Acrolein is a respiratory irritant that can be generated during cooking and is in environmental tobacco smoke. More plentiful in cigarette smoke than polycyclic aromatic hydrocarbons (PAH), acrolein can adduct tumor suppressor p53 (TP53) DNA and may contribute to TP53-mutations in lung cancer. Acrolein is also generated endogenously at sites of injury, and excessive breath levels (sufficient to activate metalloproteinases and increase mucin transcripts) have been detected in asthma and chronic obstructive pulmonary disease (COPD). Because of its reactivity with respiratory-lining fluid or cellular macromolecules, acrolein alters gene regulation, inflammation, mucociliary transport, and alveolar-capillary barrier integrity. In laboratory animals, acute exposures have lead to acute lung injury and pulmonary edema similar to that produced by smoke inhalation whereas lower concentrations have produced bronchial hyperreactivity, excessive mucus production, and alveolar enlargement. Susceptibility to acrolein exposure is associated with differential regulation of cell surface receptor, transcription factor, and ubiquitin-proteasome genes. Consequent to its pathophysiological impact, acrolein contributes to the morbidly and mortality associated with acute lung injury and COPD, and possibly asthma and lung cancer. Copyright © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Therapeutic effects of an anti-gravity locomotor training (AlterG) on postural balance and cerebellum structure in children with Cerebral Palsy.

    Science.gov (United States)

    Rasooli, A H; Birgani, P M; Azizi, Sh; Shahrokhi, A; Mirbagheri, M M

    2017-07-01

    We evaluated the therapeutic effects of anti-gravity locomotor treadmill (AlterG) training on postural stability in children with Cerebral Palsy (CP) and spasticity, particularly in the lower extremity. AlterG can facilitate walking by reducing the weight of CP children by up to 80%; it can also help subjects maintain an appropriate posture during the locomotor AlterG training. Thus, we hypothesized that AlterG training, for a sufficient period of time, has a potential to produce cerebellum neuroplasticity, and consequently result in an effective permanent postural stability. AlterG training was given for 45 minutes, three times a week for two months. Postural balance was evaluated using posturography. The parameters of the Romberg based posturography were extracted to quantify the Center of Balance (CoP). The neuroplasticity of Cerebellum was evaluated using a Diffusion Tensor Imaging (DTI). The evaluations were done pre- and post-training. The Fractional Anisotropy (FA) feature was used for quantifying structural changes in the cerebellum. The results showed that AlterG training resulted in an increase in average FA value of the cerebellum white matter following the training. The results of the posturography evaluations showed a consistent improvement in postural stability. These results were consistent in all subjects. Our findings indicated that the improvement in the posture was accompanied with the enhancement of the cerebellum white matter structure. The clinical implication is that AlterG training can be considered a therapeutic tool for an effective and permanent improvement of postural stability in CP children.

  19. Pulmonary pseudoneoplasms.

    Science.gov (United States)

    Yi, Eunhee; Aubry, Marie-Christine

    2010-03-01

    Not uncommonly, a surgical pathologist will be requested to review excised material, with a clinical diagnosis of cancer, in which no malignancy can be identified. Often, sampling may be the issue. However, different nonneoplastic processes may mimic cancer clinically and not be recognized histologically. These are commonly referred to as pseudoneoplasms and can involve the lung, pleura, and mediastinum. To review the most commonly encountered pseudoneoplasms of the thoracic cavity in surgical pathology and discuss the main differential diagnosis. Literature and personal review of cases with focus on inflammatory pseudotumors of the lung, organizing pneumonia, nodular lymphoid hyperplasia, apical cap, round atelectasis, and sclerosing mediastinitis with its pulmonary counterpart, hyalinizing granuloma. When reviewing specimens that appear nondiagnostic for malignancy, it is important to consider one of these pseudoneoplasms in the differential diagnosis as they may explain the clinical and radiologic information.

  20. Clinical and x-ray diagnosis of pulmonary aspergilloma

    International Nuclear Information System (INIS)

    Alyazov, S.I.; Manafov, S.S.; Gurbanaliev, I.G.

    1981-01-01

    Clinical and X-ray peculiarities of pulmonary alterations in patients with aspergilloma are analyzed. The diagnosis of pulmonary aspergilloma is shown to be based on the sum of characte-- ristic clinical and X-ray symptoms and data of mycologic sputum investigations and diffuse precipitation reaction according to Ouchterloni [ru

  1. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...

  2. Retrograde pulmonary arteriography

    International Nuclear Information System (INIS)

    Calcaterra, G.; Lam, J.; Losekoot, T.G.

    1984-01-01

    The authors performed retrograde pulmonary arteriography by means of a pulmonary venous wedge injection in 10 patients with no demonstrable intrapericardial pulmonary arteries by 'conventional' angiographic techniques. In all cases but one, the procedure demonstrated the feasibility of a further operation. No complications were observed. Retrograde pulmonary arteriography is an important additional method for determining the existence of surgically accessible pulmonary arteries when other techniques have failed. (Auth.)

  3. Performance of a Natural Language Processing (NLP) Tool to Extract Pulmonary Function Test (PFT) Reports from Structured and Semistructured Veteran Affairs (VA) Data.

    Science.gov (United States)

    Sauer, Brian C; Jones, Barbara E; Globe, Gary; Leng, Jianwei; Lu, Chao-Chin; He, Tao; Teng, Chia-Chen; Sullivan, Patrick; Zeng, Qing

    2016-01-01

    Pulmonary function tests (PFTs) are objective estimates of lung function, but are not reliably stored within the Veteran Health Affairs data systems as structured data. The aim of this study was to validate the natural language processing (NLP) tool we developed-which extracts spirometric values and responses to bronchodilator administration-against expert review, and to estimate the number of additional spirometric tests identified beyond the structured data. All patients at seven Veteran Affairs Medical Centers with a diagnostic code for asthma Jan 1, 2006-Dec 31, 2012 were included. Evidence of spirometry with a bronchodilator challenge (BDC) was extracted from structured data as well as clinical documents. NLP's performance was compared against a human reference standard using a random sample of 1,001 documents. In the validation set NLP demonstrated a precision of 98.9 percent (95 percent confidence intervals (CI): 93.9 percent, 99.7 percent), recall of 97.8 percent (95 percent CI: 92.2 percent, 99.7 percent), and an F-measure of 98.3 percent for the forced vital capacity pre- and post pairs and precision of 100 percent (95 percent CI: 96.6 percent, 100 percent), recall of 100 percent (95 percent CI: 96.6 percent, 100 percent), and an F-measure of 100 percent for the forced expiratory volume in one second pre- and post pairs for bronchodilator administration. Application of the NLP increased the proportion identified with complete bronchodilator challenge by 25 percent. This technology can improve identification of PFTs for epidemiologic research. Caution must be taken in assuming that a single domain of clinical data can completely capture the scope of a disease, treatment, or clinical test.

  4. Functional pulmonary atresia in newborn with normal intracardiac anatomy: Successful treatment with inhaled nitric oxide and pulmonary vasodilators

    Directory of Open Access Journals (Sweden)

    Gürkan Altun

    2013-01-01

    Full Text Available Functional pulmonary atresia is characterized by a structurally normal pulmonary valve that does not open during right ventricular ejection. It is usually associated with Ebstein′s anomaly, Uhl′s anomaly, neonatal Marfan syndrome and tricuspid valve dysplasia. However, functional pulmonary atresia is rarely reported in newborn with anatomically normal heart. We report a newborn with functional pulmonary atresia who had normal intracardiac anatomy, who responded to treatment with nitric oxide and other vasodilator therapy successfully.

  5. [Diaphragm dysfunction in patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Verheul, A.J.; Dekhuijzen, P.N.R.

    2003-01-01

    Chronic obstructive pulmonary disease (COPD) is characterised by alterations in the airways and lung parenchyma resulting in an increased respiratory workload. Besides an increased load and hyperinflation of the thorax, additional factors, such as systemic inflammation, oxidative stress, hypoxia and

  6. Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease

    Science.gov (United States)

    Hunt, James M.; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P. A.; Stacher, Elvira; Gandjeva, Marina R.; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B.; Kuebler, Wolfgang M.

    2013-01-01

    Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries. PMID:24039255

  7. Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease.

    Science.gov (United States)

    Hunt, James M; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P A; Stacher, Elvira; Gandjeva, Marina R; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B; Kuebler, Wolfgang M; Tuder, Rubin M

    2013-11-15

    Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries.

  8. Genetic Structure and Drug Susceptibility Patterns of Mycobacterium tuberculosis Complex Strains Responsible of Human Pulmonary Tuberculosis in the Major Rearing Region in Cameroon

    Directory of Open Access Journals (Sweden)

    Francioli Koro Koro

    2016-01-01

    Full Text Available Background. Cameroon this last decade continues to present a low contribution of M. africanum and M. bovis in human tuberculosis (TB, while M. bovis was prevalent in cattle but all these pieces of information only concerned West and Center regions. Methods. We carried out the first study in Adamaoua, one of the most rearing regions of Cameroon, on the genetic structure and drug susceptibility of the MTBC strains isolated from newly diagnosed sputum smear-positive patients aged 15 years and above. For that purpose, spoligotyping, a modified 15 standard MIRU/VNTR loci typing, and the proportion method were used. Results. Four hundred and thirty-seven MTBC isolates were analyzed by spoligotyping. Of these, 423 were identified as M. tuberculosis, within the Cameroon family being dominant with 278 (65.7% isolates; twelve (2.75% isolates were classified as M. africanum and two as M. bovis. MIRU/VNTR typing of the most prevalent sublineage (SIT 61 suggested that this lineage is not a unique clone as thought earlier but could constitute a group of strains implicated to different pocket of TB transmission. Only M. tuberculosis sublineages were associated with antituberculosis drug resistance. Conclusion. These results showed the weak contribution of M. africanum and M. bovis to human active pulmonary tuberculosis in Cameroon even in the rearing region.

  9. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form beta-turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis...... is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP......-C, and studied their structural behaviour in solution and in phospholipid bilayers and monolayers. In these peptides, leucine at position 1 of both sequences has been replaced by tryptophan in order to allow their study by fluorescence spectroscopy. Far-u.v. circular dichroism spectra of the peptides in aqueous...

  10. Importance of doping, dopant distribution, and defects on electronic band structure alteration of metal oxide nanoparticles: Implications for reactive oxygen species

    International Nuclear Information System (INIS)

    Saleh, Navid B.; Milliron, Delia J.; Aich, Nirupam; Katz, Lynn E.; Liljestrand, Howard M.; Kirisits, Mary Jo

    2016-01-01

    Metal oxide nanoparticles (MONPs) are considered to have the potency to generate reactive oxygen species (ROS), one of the key mechanisms underlying nanotoxicity. However, the nanotoxicology literature demonstrates a lack of consensus on the dominant toxicity mechanism(s) for a particular MONP. Moreover, recent literature has studied the correlation between band structure of pristine MONPs to their ability to introduce ROS and thus has downplayed the ROS-mediated toxicological relevance of a number of such materials. On the other hand, material science can control the band structure of these materials to engineer their electronic and optical properties and thereby is constantly modulating the pristine electronic structure. Since band structure is the fundamental material property that controls ROS-producing ability, band tuning via introduction of dopants and defects needs careful consideration in toxicity assessments. This commentary critically evaluates the existing material science and nanotoxicity literature and identifies the gap in our understanding of the role of important crystal structure features (i.e., dopants and defects) on MONPs' electronic structure alteration as well as their ROS-generation capability. Furthermore, this commentary provides suggestions on characterization techniques to evaluate dopants and defects on the crystal structure and identifies research needs for advanced theoretical predictions of their electronic band structures and ROS-generation abilities. Correlation of electronic band structure and ROS will not only aid in better mechanistic assessment of nanotoxicity but will be impactful in designing and developing ROS-based applications ranging from water disinfection to next-generation antibiotics and even cancer therapeutics. - Highlights: • Metal oxide nanoparticles (MONPs) produce reactive oxygen species (ROS) • Band structure of pristine MONPs is different than those with dopants/defects • Dopants/defects modulate

  11. Importance of doping, dopant distribution, and defects on electronic band structure alteration of metal oxide nanoparticles: Implications for reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, Navid B., E-mail: navid.saleh@utexas.edu [Department of Civil, Architectural, and Environmental Engineering, University of Texas, Austin, TX 78712 (United States); Milliron, Delia J. [McKetta Department of Chemical Engineering, University of Texas, Austin, TX 78712 (United States); Aich, Nirupam [Department of Civil, Structural and Environmental Engineering, University at Buffalo, The State University of New York, Buffalo, NY, 14260 (United States); Katz, Lynn E.; Liljestrand, Howard M.; Kirisits, Mary Jo [Department of Civil, Architectural, and Environmental Engineering, University of Texas, Austin, TX 78712 (United States)

    2016-10-15

    Metal oxide nanoparticles (MONPs) are considered to have the potency to generate reactive oxygen species (ROS), one of the key mechanisms underlying nanotoxicity. However, the nanotoxicology literature demonstrates a lack of consensus on the dominant toxicity mechanism(s) for a particular MONP. Moreover, recent literature has studied the correlation between band structure of pristine MONPs to their ability to introduce ROS and thus has downplayed the ROS-mediated toxicological relevance of a number of such materials. On the other hand, material science can control the band structure of these materials to engineer their electronic and optical properties and thereby is constantly modulating the pristine electronic structure. Since band structure is the fundamental material property that controls ROS-producing ability, band tuning via introduction of dopants and defects needs careful consideration in toxicity assessments. This commentary critically evaluates the existing material science and nanotoxicity literature and identifies the gap in our understanding of the role of important crystal structure features (i.e., dopants and defects) on MONPs' electronic structure alteration as well as their ROS-generation capability. Furthermore, this commentary provides suggestions on characterization techniques to evaluate dopants and defects on the crystal structure and identifies research needs for advanced theoretical predictions of their electronic band structures and ROS-generation abilities. Correlation of electronic band structure and ROS will not only aid in better mechanistic assessment of nanotoxicity but will be impactful in designing and developing ROS-based applications ranging from water disinfection to next-generation antibiotics and even cancer therapeutics. - Highlights: • Metal oxide nanoparticles (MONPs) produce reactive oxygen species (ROS) • Band structure of pristine MONPs is different than those with dopants/defects • Dopants/defects modulate

  12. Dorsal raphe nucleus of brain in the rats flown in space inflight and postflight alteration of structure

    Science.gov (United States)

    Krasnov, I.

    The structure of brain dorsal raphe nucleus (DRN) was studied in the rats flown in space aboard Space Shuttle "Columbia" (STS-58, SLS-2 program) and dissected on day 13 of the mission ("inflight" rats) and in 5-6 hours after finishing 14-day flight ("postflight" rats). The brain of "inflight" rats were excised after decapitation, sectioned sagitally halves of brain were fixed by immersion in 2,5 % glutaraldehyde in 0.1 M cacodylate buffer pH 7.3 at 4°C and kept in the flight at 4°C. After landing the brain frontal 0.5 mm sections from DRN area were osmificated and embedded in araldite at NASA ARC. The brains of "postflight": and control rats were underwent to the same procedure. Electronmicroscopical analysis, computer morphometry and glial cell count were performed at Moscow. In DRN neuropil of "inflight" rats the most part of axo-dendritic synapses were surrounded by glia cell processes and had decreased electron density of pre- and postsynaptic membrane and pronounced diminution of synaptic vesicle amount while dendrites were characterized by decrease in matrix electron density and microtubule quantity that in total indicates the decline of afferent flow reaching DRN neurons in microgravity. In DRN neurons of "inflight" rats all mitochondria were characterized by evenly increased dimensions, decreased matrix electron density, small amount of short and far- between located cristae and enlarged intermembrane and intercristae spaces, that in total points out low level of coupling of oxidation to phosphorilation, decrease in energy supply of neuron. Amount of ribosome in cytoplasm was significantly decreased indicating lower lever of biosynthetic processes. The last is supported by diminished dimensions of neuronal body, nucleus and nucleolus (place of r RNA synthesis), cross section area of that were reduced in DRN neurons of "inflight" rats by 18.8 % (p functional activity of DRN - main serotoniner gic center of brain and in combination with the data (Krasnov et

  13. Altered structure and function of adipose tissue in long-lived mice with growth hormone-related mutations.

    Science.gov (United States)

    Darcy, Justin; McFadden, Samuel; Bartke, Andrzej

    2017-04-03

    A major focus of biogerontology is elucidating the role(s) of the endocrine system in aging and the accumulation of age-related diseases. Endocrine control of mammalian longevity was first reported in Ames dwarf (Prop1 df ) mice, which are long-lived due to a recessive Prop1 loss-of-function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin. Following this report, several other GH-related mutants with altered longevity have been described including long-lived Snell dwarf and growth hormone receptor knockout mice, and short-lived GH overexpressing transgenic mice. One of the emerging areas of interest in these mutant mice is the role of adipose tissue in their altered healthspan and lifespan. Here, we provide an overview of the alterations in body composition of GH-related mutants, as well as the altered thermogenic potential of their brown adipose tissue and the altered cellular senescence and adipokine production of their white adipose tissue.

  14. Interaction of a common painkiller piroxicam and copper-piroxicam with chromatin causes structural alterations accompanied by modulation at the epigenomic/genomic level.

    Science.gov (United States)

    Goswami, Sathi; Sanyal, Sulagna; Chakraborty, Payal; Das, Chandrima; Sarkar, Munna

    2017-08-01

    NSAIDs are the most common class of painkillers and anti-inflammatory agents. They also show other functions like chemoprevention and chemosuppression for which they act at the protein but not at the genome level since they are mostly anions at physiological pH, which prohibit their approach to the poly-anionic DNA. Complexing the drugs with bioactive metal obliterate their negative charge and allow them to bind to the DNA, thereby, opening the possibility of genome level interaction. To test this hypothesis, we present the interaction of a traditional NSAID, Piroxicam and its copper complex with core histone and chromatin. Spectroscopy, DLS, and SEM studies were applied to see the effect of the interaction on the structure of histone/chromatin. This was coupled with MTT assay, immunoblot analysis, confocal microscopy, micro array analysis and qRT-PCR. The interaction of Piroxicam and its copper complex with histone/chromatin results in structural alterations. Such structural alterations can have different biological manifestations, but to test our hypothesis, we have focused only on the accompanied modulations at the epigenomic/genomic level. The complex, showed alteration of key epigenetic signatures implicated in transcription in the global context, although Piroxicam caused no significant changes. We have correlated such alterations caused by the complex with the changes in global gene expression and validated the candidate gene expression alterations. Our results provide the proof of concept that DNA binding ability of the copper complexes of a traditional NSAID, opens up the possibility of modulations at the epigenomic/genomic level. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP...... the packing of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) monolayers, the effects being always higher in anionic than in zwitterionic lipids, and also substantially higher in films containing canine peptide in comparison to porcine peptide. Acylation of cysteines at the N...

  16. Dermatan Sulfate Epimerase 1-Deficient Mice Have Reduced Content and Changed Distribution of Iduronic Acids in Dermatan Sulfate and an Altered Collagen Structure in Skin

    DEFF Research Database (Denmark)

    Maccarana, M.; Kalamajski, S.; Kongsgaard, M.

    2009-01-01

    Dermatan sulfate epimerase 1 (DS-epi1) and DS-epi2 convert glucuronic acid to iduronic acid in chondroitin/dermatan sulfate biosynthesis. Here we report on the generation of DS-epi1-null mice and the resulting alterations in the chondroitin/dermatan polysaccharide chains. The numbers of long blocks...... of adjacent iduronic acids are greatly decreased in skin decorin and biglycan chondroitin/dermatan sulfate, along with a parallel decrease in iduronic-2-O-sulfated-galactosamine-4-O-sulfated structures. Both iduronic acid blocks and iduronic acids surrounded by glucuronic acids are also decreased in versican......-derived chains. DS-epi1-deficient mice are smaller than their wild-type littermates but otherwise have no gross macroscopic alterations. The lack of DS-epi1 affects the chondroitin/dermatan sulfate in many proteoglycans, and the consequences for skin collagen structure were initially analyzed. We found...

  17. Pulmonary artery remodeling differs in hypoxia- and monocrotaline-induced pulmonary hypertension

    NARCIS (Netherlands)

    van Suylen, R. J.; Smits, J. F.; Daemen, M. J.

    1998-01-01

    In the present study we analyzed structural characteristics of muscular pulmonary arteries and arterioles in two classic models of pulmonary hypertension, the rat hypoxia and monocrotaline models. We hypothesized that an increase in medial cross-sectional area would result in reduction of the lumen

  18. How Is Pulmonary Hypertension Treated?

    Science.gov (United States)

    ... Home / Hypertension Pulmonary Hypertension What Is Pulmonary hypertension (PULL-mun-ary HI- ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  19. CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

    Science.gov (United States)

    Austin, John H. M.; Hogg, James C.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bankier, Alexander A.; Barr, R. Graham; Colby, Thomas V.; Galvin, Jeffrey R.; Gevenois, Pierre Alain; Coxson, Harvey O.; Hoffman, Eric A.; Newell, John D.; Pistolesi, Massimo; Silverman, Edwin K.; Crapo, James D.

    2015-01-01

    The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. © RSNA, 2015 PMID:25961632

  20. Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

    DEFF Research Database (Denmark)

    Egecioglu, E; Andersson, I J; Bollano, E

    2007-01-01

    To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 +/- 2 vs. 20 +/- 4 mGU/ml, P ... to acetylcholine (P functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size...

  1. Alteration effect of the PGFsub(2α) inhibition on the 3H-norepinephrine release caused by α2 receptor blocking, sodium loading and 4-aminopyridine addition in isolated pulmonary arteries of rabbit

    International Nuclear Information System (INIS)

    Bunyevacs, Zs.; Toeroek, T.; Hadhazy, P.; Magyar, K.; Feher, L.; Vizi, E.Sz.

    1983-01-01

    The tritium labelled norepinephrine release was measured in isolated pulmonary artery of rabbit. If the 3 H-norepinephrine release was induced by nerves stimulated with electric current, the PGFsub(2α) inhibited the release by 62%. In the presence of Yohimbin the inhibitory effect of FGFsub(2α) was increased to 78.8%. If the Na + pump activity was reduced by potassium-free medium the PGFsub(2α) inhibition remained at 62%. In the presence of 4-aminopyridine the potassium channel was blocked and the PGFsub(2α) inhibition decreased to 32.1%. The endogen prostaglandin may serve as a modulator of the neurotransmitter release. (L.G.)

  2. Throughfall-mediated alterations to soil microbial community structure in a forest plot of homogenous soil texture, litter, and plant species composition

    Science.gov (United States)

    Van Stan, John; Rosier, Carl; Moore, Leslie; Gay, Trent; Reichard, James; Wu, Tiehang; Kan, Jinjun

    2015-04-01

    Identifying spatiotemporal influences on soil microbial community (SMC) structure is critical to our understanding of patterns in biogeochemical cycling and related ecological services (e.g., plant community structure, water quality, response to environmental change). Since forest canopy structure alters the spatiotemporal patterning of precipitation water and solute supplies to soils (via "throughfall"), is it possible that changes in SMC structure could arise from modifications in canopy elements? Our study investigates this question by monitoring throughfall water and dissolved ion supply to soils beneath a continuum of canopy structure: from large gaps (0% cover), to bare Quercus virginiana Mill. (southern live oak) canopy (~50-70%), to heavy Tillandsia usneoides L. (Spanish moss) canopy (>90% cover). Throughfall water supply diminished with increasing canopy cover, yet increased washoff/leaching of Na+, Cl-, PO43-, and SO42- from the canopy to the soils. Presence of T. usneoides diminished throughfall NO3-, but enhanced NH4+, concentrations supplied to subcanopy soils. The mineral soil horizon (0-10 cm) sampled in triplicate from locations receiving throughfall water and solutes from canopy gaps, bare canopy, and T. usneoides-laden canopy significantly differed in soil chemistry parameters (pH, Ca2+, Mg2+, CEC). Polymerase Chain Reaction-Denaturant Gradient Gel Electrophoresis (PCR-DGGE) banding patterns beneath similar canopy covers (experiencing similar throughfall dynamics) also produced high similarities per ANalyses Of SIMilarity (ANO-SIM), and clustered together when analyzed by Nonmetric Multidimensional Scaling (NMDS). These results suggest that modifications of forest canopy structures are capable of affecting mineral-soil horizon SMC structure via throughfall when canopies' biomass distribution is highly heterogeneous. As SMC structure, in many instances, relates to functional diversity, we suggest that future research seek to identify functional

  3. Hantavirus Pulmonary Syndrome (HPS)

    Science.gov (United States)

    ... to Yosemite FAQ: Non-U.S. Visitors to Yosemite History of HPS Related Links Prevent Rodent Infestations Cleaning Up After Rodents Diseases From Rodent Hantavirus Pulmonary Syndrome (HPS) Recommend on Facebook Tweet Share Compartir Hantavirus Pulmonary Syndrome (HPS) is ...

  4. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... who also suffer from PH have lower pulmonary artery pressures than those who have PH alone; despite ... Address and Privacy Pulmonary Hypertension Association 801 Roeder Road, Ste. 1000 Silver Spring, MD 20910 Patient-to- ...

  5. Are there structural alterations in the enamel organ of offspring of rats with alloxan-induced diabetes mellitus?

    OpenAIRE

    Silva-Sousa,Yara Teresinha Corrêa; Peres,Luiz Cesar; Foss,Milton César

    2003-01-01

    Enamel hypoplasia is the most common developmental defect of human teeth that may be seen in deciduous teeth of babies born to diabetic women. In the present experimental study, we analyzed the enamel organ of the mandibular incisors of the offspring of rats with alloxan-induced diabetes. By light microscopy, no alterations could be found in the enamel organ of rats born to diabetic mothers compared to normal ones, except in one case. In contrast, significant differences were detected with co...

  6. Idiopathic pulmonary hemosiderosis

    OpenAIRE

    Sunilkumar, B M; Sathishkumar, K M; Somashekhar, A R; Maiya, P P

    2010-01-01

    Recurrent or chronic pulmonary hemorrhage is rare in children. Idiopathic pulmonary hemosiderosis (IPH) manifests as hemoptysis, diffuse parenchymal infiltrates on chest radiographs and microcytic hypochromic anemia. The hemoptysis present may be mistaken for more common diseases, delaying the diagnosis and further management. Idiopathic pulmonary hemosiderosis is a disorder of unknown etiology. Treatment of IPH includes immunosuppressive drugs along with supportive measures.

  7. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

    Science.gov (United States)

    Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

    2014-01-01

    Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these

  8. Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs.

    Science.gov (United States)

    Astorga, Cristian R; González-Candia, Alejandro; Candia, Alejandro A; Figueroa, Esteban G; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V; Llanos, Aníbal J; Herrera, Emilio A

    2018-01-01

    Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs ( Ovis aries ) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg -1 .d -1 ) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk ( p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% ( p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.

  9. Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

    Directory of Open Access Journals (Sweden)

    Cristian R. Astorga

    2018-03-01

    Full Text Available Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN, a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs.Methods: Twelve lambs (Ovis aries gestated and born at highlands (3,600 m were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1 during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations.Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05. This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05 and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05. Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05. Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05.Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.

  10. Structural alterations in a component of cytochrome c oxidase and molecular evolution of pathogenic Neisseria in humans.

    Directory of Open Access Journals (Sweden)

    Marina Aspholm

    2010-08-01

    Full Text Available Three closely related bacterial species within the genus Neisseria are of importance to human disease and health. Neisseria meningitidis is a major cause of meningitis, while Neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and Neisseria lactamica is a common, harmless commensal of children. Comparative genomics have yet to yield clear insights into which factors dictate the unique host-parasite relationships exhibited by each since, as a group, they display remarkable conservation at the levels of nucleotide sequence, gene content and synteny. Here, we discovered two rare alterations in the gene encoding the CcoP protein component of cytochrome cbb(3 oxidase that are phylogenetically informative. One is a single nucleotide polymorphism resulting in CcoP truncation that acts as a molecular signature for the species N. meningitidis. We go on to show that the ancestral ccoP gene arose by a unique gene duplication and fusion event and is specifically and completely distributed within species of the genus Neisseria. Surprisingly, we found that strains engineered to express either of the two CcoP forms conditionally differed in their capacity to support nitrite-dependent, microaerobic growth mediated by NirK, a nitrite reductase. Thus, we propose that changes in CcoP domain architecture and ensuing alterations in function are key traits in successive, adaptive radiations within these metapopulations. These findings provide a dramatic example of how rare changes in core metabolic proteins can be connected to significant macroevolutionary shifts. They also show how evolutionary change at the molecular level can be linked to metabolic innovation and its reversal as well as demonstrating how genotype can be used to infer alterations of the fitness landscape within a single host.

  11. Opportunity, Geologic and Structural Context of Aqueous Alteration in Noachian Outcrops, Marathon Valley and Rim and Endeavour Crater

    Science.gov (United States)

    Crumpler, L. S.; Arvidson, R. E.; Mittlefehldt, D. W.; Jolliff, B. L.; Farrand, W. H.; Fox, V.; Golombek, M. P.

    2016-01-01

    In its 12th year of exploration and 1600 sols since arrival at the rim of the 22 km-diameter Noachian Endeavour impact crater, Mars Exploration Rover Opportunity traversed from the summit of the western rim segment "Cape Tribulation" to "Marathon Valley", a shallow trough dissecting the rim and the site of strong orbital detection of smectites. In situ analysis of the exposures within Marathon Valley is establishing some of the geologic and geochemical controls on the aqueous alteration responsible for smectite detection known to occur in crater rims throughout Noachian terrains of Mars.

  12. Dysfunction of pulmonary vascular endothelium in chronic obstructive pulmonary disease: basic considerations for future drug development.

    Science.gov (United States)

    Yang, Qin; Underwood, Malcolm J; Hsin, Michael K Y; Liu, Xiao-Cheng; He, Guo-Wei

    2008-09-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading health problems worldwide and continues to be a major cause of morbidity and mortality in developed countries. The clinical features of COPD are chronic obstructive bronchiolitis and emphysema. Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of COPD at different stages of the disease. Functional changes of pulmonary endothelial cells in COPD include antiplatelet abnormalities, anticoagulant disturbances, endothelial activation, atherogenesis, and compromised regulation of vascular tone which may adversely affect the ventilation-perfusion match in COPD. As the most important risk factor of COPD, cigarette smoking may initiate pulmonary vascular impairment through direct injury of endothelial cells or release of inflammatory mediators. Morphological changes such as denudation of endothelium and endothelial cell apoptosis have been observed in the pulmonary vasculature in COPD patients as well as functional alterations. Changes in the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin, selectins, and adhesion molecules in pulmonary endothelial cells as well as complex regulation and interaction of vasoactive substances and growth factors released from endothelium may underlie the mechanisms of pulmonary endothelial dysfunction in COPD. The mechanism of endothelial repair/regeneration in COPD, although not fully understood, may involve upregulation of vascular endothelial growth factors in the early stages along with an increased number of bone marrow-derived progenitor cells. These factors should be taken into account when developing new strategies for the pharmacological therapy of patients with COPD.

  13. DNA methylation changes separate allergic patients from healthy controls and may reflect altered CD4+ T-cell population structure.

    Directory of Open Access Journals (Sweden)

    Colm E Nestor

    2014-01-01

    Full Text Available Altered DNA methylation patterns in CD4(+ T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR is an optimal disease model for the study of DNA methylation because of its well-defined phenotype and etiology. We generated genome-wide DNA methylation (N(patients = 8, N(controls = 8 and gene expression (N(patients = 9, Ncontrols = 10 profiles of CD4(+ T-cells from SAR patients and healthy controls using Illumina's HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (N(patients = 12, N(controls = 12, but not by gene expression (N(patients = 21, N(controls = 21 was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (N(patients = 35 and controls (N(controls = 12, which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4(+ T cells.

  14. Adolescent Risk Behaviours and Mealtime Routines: Does Family Meal Frequency Alter the Association between Family Structure and Risk Behaviour?

    Science.gov (United States)

    Levin, Kate A.; Kirby, Joanna; Currie, Candace

    2012-01-01

    Family structure is associated with a range of adolescent risk behaviours, with those living in both parent families generally faring best. This study describes the association between family structure and adolescent risk behaviours and assesses the role of the family meal. Data from the 2006 Health Behaviour in School-Aged Children survey were…

  15. Surgical management of penetrating pulmonary injuries

    OpenAIRE

    Asensio Juan A; Petrone Patrizio

    2009-01-01

    Abstract Chest injuries were reported as early as 3000 BC in the Edwin Smith Surgical Papyrus. Ancient Greek chronicles reveal that they had anatomic knowledge of the thoracic structures. Even in the ancient world, most of the therapeutic modalities for chest wounds and traumatic pulmonary injuries were developed during wartime. The majority of lung injuries can be managed non-operatively, but pulmonary injuries that require operative surgical intervention can be quite challenging. Recent pro...

  16. Amino acid duplication in the coiled-coil structure of collagen XVII alters its maturation and trimerization causing mild junctional epidermolysis bullosa.

    Science.gov (United States)

    Kroeger, Jasmin K; Hofmann, Silke C; Leppert, Juna; Has, Cristina; Franzke, Claus-Werner

    2017-02-01

    The function and stability of collagens depend on the accurate triple helix formation of three distinct polypeptide chains. Disruption of this triple-helical structure can result in connective-tissue disorders. Triple helix formation is thought to depend on three-stranded coiled-coil oligomerization sites within non-collagenous domains. However, only little is known about the physiological relevance of these coiled-coil structures. Transmembrane collagen XVII, also known as 180 kDa bullous pemphigoid antigen provides mechanical stability through the anchorage of epithelial cells to the basement membrane. Mutations in the collagen XVII gene, COL17A1, cause junctional epidermolysis bullosa (JEB), characterized by chronic trauma-induced skin blistering. Here we exploited a novel naturally occurring COL17A1 mutation, leading to an in-frame lysine duplication within the coiled-coil structure of the juxtamembranous NC16A domain of collagen XVII, which resulted in a mild phenotype of JEB due to reduced membrane-anchored collagen XVII molecules. This mutation causes structural changes in the mutant molecule and interferes with its maturation. The destabilized coiled-coil structure of the mutant collagen XVII unmasks a furin cleavage site that results in excessive and non-physiological ectodomain shedding during its maturation. Furthermore, it decreases its triple-helical stability due to defective coiled-coil oligomerization, which makes it highly susceptible to proteolytic degradation. As a consequence of altered maturation and decreased stability of collagen XVII trimers, reduced collagen XVII is incorporated into the cell membrane, resulting in compromised dermal-epidermal adhesion. Taken together, using this genetic model, we provide the first proof that alteration of the coiled-coil structure destabilizes oligomerization and impairs physiological shedding of collagen XVII in vivo. © The Author 2016. Published by Oxford University Press. All rights reserved. For

  17. Multidetector computed tomography pulmonary angiography in childhood acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun Xiang; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Schoepf, U.J. [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Department of Pediatrics, Charleston, SC (United States); Chowdhury, Shahryar M. [Medical University of South Carolina, Department of Pediatrics, Charleston, SC (United States); Fox, Mary A. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States)

    2015-09-15

    Pulmonary embolism is a life-threatening condition affecting people of all ages. Multidetector row CT pulmonary angiography has improved the imaging of pulmonary embolism in both adults and children and is now regarded as the routine modality for detection of pulmonary embolism. Advanced CT pulmonary angiography techniques developed in recent years, such as dual-energy CT, have been applied as a one-stop modality for pulmonary embolism diagnosis in children, as they can simultaneously provide anatomical and functional information. We discuss CT pulmonary angiography techniques, common and uncommon findings of pulmonary embolism in both conventional and dual-energy CT pulmonary angiography, and radiation dose considerations. (orig.)

  18. The structural alteration and aggregation propensity of glycated lens crystallins in the presence of calcium: Importance of lens calcium homeostasis in development of diabetic cataracts

    Science.gov (United States)

    ZM, Sara Zafaranchi; Khoshaman, Kazem; Masoudi, Raheleh; Hemmateenejad, Bahram; Yousefi, Reza

    2017-01-01

    The imbalance of the calcium homeostasis in the lenticular tissues of diabetic patients is an important risk factor for development of cataract diseases. In the current study, the impact of elevated levels of calcium ions were investigated on structure and aggregation propensity of glycated lens crystallins using gel electrophoresis and spectroscopic assessments. The glycated proteins indicated significant resistance against calcium-induced structural insults and aggregation. While, glycated crystallins revealed an increased conformational stability; a slight instability was observed for these proteins upon interaction with calcium ions. Also, in the presence of calcium, the proteolytic pattern of native crystallins was altered and that of glycated protein counterparts remained almost unchanged. According to results of this study it is suggested that the structural alteration of lens crystallins upon glycation may significantly reduce their calcium buffering capacity in eye lenses. Therefore, under chronic hyperglycemia accumulation of this cataractogenic metal ion in the lenticular tissues may subsequently culminate in activation of different pathogenic pathways, leading to development of lens opacity and cataract diseases.

  19. Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts.

    Science.gov (United States)

    Kim, Gun-Dong; Lee, Seung Eun; Kim, Tae-Ho; Jin, Young-Ho; Park, Yong Seek; Park, Cheung-Seog

    2012-04-01

    Cigarette smoke (CS) causes harmful alterations in the lungs and airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). In addition to COPD, active cigarette smoking causes other respiratory diseases and diminishes health status. Furthermore, recent studies show that, α, β-unsaturated aldehyde acrolein in CS induces the production of interleukin (IL)-8, which is known to be related to bronchitis, rhinitis, pulmonary fibrosis, and asthma. In addition, lung and pulmonary fibroblasts secrete IL-8, which has a chemotactic effect on leukocytes, and which in turn, play a critical role in lung inflammation. On the other hand, melatonin regulates circadian rhythm homeostasis in humans and has many other effects, which include antioxidant and anti-inflammatory effects, as demonstrated by the reduced expressions of iNOS, IL-1β, and IL-6 and increased glutathione (GSH) and superoxide dismutase activities. In this study, we investigated whether melatonin suppresses acrolein-induced IL-8 secretion in human pulmonary fibroblasts (HPFs). It was found that acrolein-induced IL-8 production was accompanied by increased levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK1/2) in HPFs, and that melatonin suppressed IL-8 production in HPFs. These results suggest that melatonin suppresses acrolein-induced IL-8 production via ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs. © 2011 John Wiley & Sons A/S.

  20. Heterologous expression ofa histone-like protein from Streptococcus intermedius in Escherichia coli alters the nucleoid structure and inhibits the growth of E. coli.

    Science.gov (United States)

    Liu, Dali; Yumoto, Hiromichi; Murakami, Keiji; Hirota, Katsuhiko; Kayama, Shizuo; Taniguchi, Tomonori; Yamamoto, Akitake; Ono, Tsuneko; Matsuo, Takashi; Miyake, Yoichiro

    2008-11-01

    Escherichia coli failed to survive after transformation with a Streptococcus intermedius histone-like protein gene (Si-hlp) and its promoter-harbored plasmid. The promoter function of Si-hlp in E. coli was determined using enhanced green fluorescence protein (egfp) gene as a reporter. The inhibitory effect of Si-HLP on E. coli viability was verified by a tetracycline-inducible gene expression system. Further study suggested that Si-HLP may alter the bacterial nucleoid structure, leading to the growth inhibition of E. coli.

  1. Importance of doping, dopant distribution, and defects on electronic band structure alteration of metal oxide nanoparticles: Implications for reactive oxygen species.

    Science.gov (United States)

    Saleh, Navid B; Milliron, Delia J; Aich, Nirupam; Katz, Lynn E; Liljestrand, Howard M; Kirisits, Mary Jo

    2016-10-15

    Metal oxide nanoparticles (MONPs) are considered to have the potency to generate reactive oxygen species (ROS), one of the key mechanisms underlying nanotoxicity. However, the nanotoxicology literature demonstrates a lack of consensus on the dominant toxicity mechanism(s) for a particular MONP. Moreover, recent literature has studied the correlation between band structure of pristine MONPs to their ability to introduce ROS and thus has downplayed the ROS-mediated toxicological relevance of a number of such materials. On the other hand, material science can control the band structure of these materials to engineer their electronic and optical properties and thereby is constantly modulating the pristine electronic structure. Since band structure is the fundamental material property that controls ROS-producing ability, band tuning via introduction of dopants and defects needs careful consideration in toxicity assessments. This commentary critically evaluates the existing material science and nanotoxicity literature and identifies the gap in our understanding of the role of important crystal structure features (i.e., dopants and defects) on MONPs' electronic structure alteration as well as their ROS-generation capability. Furthermore, this commentary provides suggestions on characterization techniques to evaluate dopants and defects on the crystal structure and identifies research needs for advanced theoretical predictions of their electronic band structures and ROS-generation abilities. Correlation of electronic band structure and ROS will not only aid in better mechanistic assessment of nanotoxicity but will be impactful in designing and developing ROS-based applications ranging from water disinfection to next-generation antibiotics and even cancer therapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Molecular and cellular mechanisms of pulmonary fibrosis

    Science.gov (United States)

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  3. Scanning electron microscopy of vascular corrosion casts and histologic examination of pulmonary microvasculature in dogs with dirofilariosis.

    Science.gov (United States)

    Ninomiya, Hiroyoshi; Wakao, Yoshito

    2002-11-01

    To characterize structural changes in pulmonary vessels of dogs with dirofilariosis. 8 dogs with dirofilariosis and 2 unaffected control dogs. Pulmonary artery pressure was measured in affected dogs, and dogs then were euthanatized. Scanning electron microscopy was used to examine vascular corrosion casts of pulmonary vasculature. Tissue sections of pulmonary vasculature were evaluated by use of histologic examination. Pulmonary artery pressure was higher in dogs with severely affected pulmonary vessels. In tissue sections, dilatation, as well as lesions in the tunica intima and proliferative lesions resulting in constriction or obstruction, were frequently observed in branches of the pulmonary artery. Numerous dilated bronchial arteries were observed around affected pulmonary arteries. Hyperplastic venous sphincters were observed in small pulmonary veins and venules. In corrosion casts, affected pulmonary lobar arteries had dilatation, pruning, abnormal tapering, constriction, and obstruction. In small arteries and arterioles, surface structures representing aneurisms and edema were seen. Bronchial arteries were well developed and extremely dilated, and they formed numerous anastomoses with pulmonary arteries at all levels, from the pulmonary trunk to peripheral vessels. Capillaries in the lungs were dilated with little structural change. Small pulmonary veins and venules had irregular annular constrictions that were caused by hyperplastic smooth muscle cells of venous sphincters. Scanning electron microscopy of microvascular casts delineated links between the bronchial and pulmonary circulations in dogs with dirofilariosis. Results of scanning electron microscopy provided a structural explanation for the development of pulmonary circulatory disturbances and pulmonary hypertension in dogs affected by dirofilariosis.

  4. Alterations in archaeological bones thermally treated: structure and morphology; Alteraciones en huesos arqueologicos termicamente tratados: estructura y morfologia

    Energy Technology Data Exchange (ETDEWEB)

    Pijoan, C.M.; Mansilla, J.; Leboreiro, I. [Direccion de Antropologia Fisica, INAH, Gandhi s/n, Polanco, 11560 Mexico D. F. (Mexico); Lara, V.H. [Universidad Autonoma Metropolitana-lztapalapa, Michoacan esquina La Purisima, Apdo.Postal 55-534, Mexico D. F. (Mexico); Bosch, P. [Instituto de Investigaciones en Materiales, UNAM, Circuito Exterior, Ciudad Universitaria, 04510 Mexico D. F. (Mexico)

    2004-07-01

    Archaeological bones found close to Mexico city (Tlatelcomila) have been characterized by X-ray Diffraction, Small Angle X-ray Spectroscopy and Scanning Electron Microscopy. These techniques, which are not conventionally used in archaeological research, provided useful information. The boiled bones were clearly distinguished from grilled bones. The degree of deterioration of the bone structure was quantified through parameters such as gyration radius or fractal dimension. The morphology followed the structural modifications and changes resulting from thermic exposure. (Author) 23 refs., 1 tab., 2 figs.

  5. A chemometric analysis of ligand-induced changes in intrinsic fluorescence of folate binding protein indicates a link between altered conformational structure and physico-chemical characteristics

    DEFF Research Database (Denmark)

    Bruun, Susanne W; Holm, Jan; Hansen, Steen Ingemann

    2009-01-01

    Ligand binding alters the conformational structure and physico-chemical characteristics of bovine folate binding protein (FBP). For the purpose of achieving further information we analyzed ligand (folate and methotrexate)-induced changes in the fluorescence landscape of FBP. Fluorescence excitation...... of folate accords fairly well with the disappearance of strongly hydrophobic tryptophan residues from the solvent-exposed surface of FBP. The PARAFAC has thus proven useful to establish a hitherto unexplained link between parallel changes in conformational structure and physico-chemical characteristics...... of FBP induced by folate binding. Parameters for ligand binding derived from PARAFAC analysis of the fluorescence data were qualitatively and quantitatively similar to those obtained from binding of radiofolate to FBP. Herein, methotrexate exhibited a higher affinity for FBP than in competition...

  6. Alterations in emotion generation and regulation neurocircuitry in depression and eating disorders: A comparative review of structural and functional neuroimaging studies.

    Science.gov (United States)

    Donofry, Shannon D; Roecklein, Kathryn A; Wildes, Jennifer E; Miller, Megan A; Erickson, Kirk I

    2016-09-01

    Major depression and eating disorders (EDs) are highly co-morbid and may share liability. Impaired emotion regulation may represent a common etiological or maintaining mechanism. Research has demonstrated that depressed individuals and individuals with EDs exhibit impaired emotion regulation, with these impairments being associated with changes in brain structure and function. The goal of this review was to evaluate findings from neuroimaging studies of depression and EDs to determine whether there are overlapping alterations in the brain regions known to be involved in emotion regulation, evidence of which would aid in the diagnosis and treatment of these conditions. Our review of the literature suggests that depression and EDs exhibit common structural and functional alterations in brain regions involved in emotion regulation, including the amygdala, ventral striatum and nucleus accumbens, anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. We present preliminary support for a shared etiological mechanism. Future studies should consider manipulating emotion regulation in a sample of individuals with depression and EDs to better characterize abnormalities in these brain circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Alterations in collagen structure in hypermobility and Ehlers-Danlos syndromes detected by Raman spectroscopy in vivo

    Science.gov (United States)

    Johansson, Carina K.; Gniadecka, Monika; Ullman, Susanne; Halberg, Poul; Kobayasi, Takasi; Wulf, Hans Christian

    2000-11-01

    Patients with hypermobility syndrome (HS) and Ehlers-Danlos syndrome (EDS) were investigated by means of in vivo near- infrared Fourier-transform Raman spectroscopy. HS is a benign and common condition (up to 5 percent of the population of the Western World). EDS is a rare, inherited connective tissue disease characterized by joint hypermobility, skin hyperextensibility, and other, occasionally serious, organ changes. EDS and HS may be related disorders. We investigated 13 patients with HS, 8 patients with EDS, and 24 healthy volunteers by means of in vivo Raman spectroscopy. The patients were classified according to Beighton and Holzberg et al. No difference in age between the three groups was found (HS 41 (33-49), EDS 36 (25-47), controls 37 (31-42); mean, 95% confidence intervals, respectively). Spectral differences were found in the intensity of the amide-III bands around 1245 and 1270 cm-1 in HS and EDS compared with healthy skin (Kruskal-Wallis, p equals 0,02 for intensity ratios (I1245/I1270) between the investigated groups). To elucidate the character of the alterations in the amide-III bands a curve fitting procedure was applied. In conclusion, Raman spectroscopy may aid in the diagnosis of HS and EDS. Moreover the technique may be useful for analyzing the molecular changes occurring in these syndromes.

  8. Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead to changes in mouse tendon structure

    DEFF Research Database (Denmark)

    Nielsen, R H; Clausen, N M; Schjerling, P

    2014-01-01

    RNA expression (targets: GAPDH, RPLP0, IGF-IEa, IGF-IR, COL1A1, COL3A1, TGF-β1, TGF-β2, TGF-β3, versican, scleraxis, tenascin C, fibronectin, fibromodulin, decorin) in the Achilles tendon, and the mRNA expression was also measured in calf muscle (same targets as tendon plus IGF-IEb, IGF-IEc). We found that GHR......The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is an important stimulator of collagen synthesis in connective tissue, but the effect of chronically altered GH/IGF-I levels on connective tissue of the muscle-tendon unit is not known. We studied three groups of mice; 1) giant......-/- mice had significantly lower collagen fibril volume fraction in Achilles tendon, as well as decreased mRNA expression of IGF-I isoforms and collagen types I and III in muscle compared to CTRL. In contrast, the mRNA expression of IGF-I isoforms and collagens in bGH mice was generally high in both tendon...

  9. Management of Pulmonary Nodules

    OpenAIRE

    Arvin Aryan

    2010-01-01

    Pulmonary nodule characterization is currently being redefined as new clinical, radiological and pathological data are reported, necessitating a reevaluation of the clinical management."nIn approach to an incidentally detected pulmonary nodule, we should consider that there are different risk situations, different lesion morphologies, and different sizes with various management options."nIn this session we will review the different risk situations for patients with pulmonary nodules...

  10. Pulmonary valvuloplasty for pulmonary atresia-restrictive ventricular septal defect.

    Science.gov (United States)

    Reshmi, Liza Jose; Gadhinglajkar, Shrinivas; Mathew, Thomas; Venkateshwaran, Subramanian; Sreedhar, Rupa; Dharan, Baiju

    2016-02-01

    Pulmonary atresia with restrictive ventricular septal defect is a rare congenital cardiac anomaly. A Blalock-Taussig shunt and surgical perforation of the atretic pulmonary valve is often performed as the initial palliation. We present our experience of utilizing both transesophageal and epicardial echocardiography during surgical pulmonary valvuloplasty in a 22-day-old neonate with pulmonary atresia with restrictive ventricular septal defect. The atretic pulmonary valve was perforated using a sheath introduced through the pulmonary artery. © The Author(s) 2014.

  11. Climate change alters the structure of arctic marine food webs due to poleward shifts of boreal generalists

    Science.gov (United States)

    Kortsch, Susanne; Primicerio, Raul; Fossheim, Maria; Dolgov, Andrey V.; Aschan, Michaela

    2015-01-01

    Climate-driven poleward shifts, leading to changes in species composition and relative abundances, have been recently documented in the Arctic. Among the fastest moving species are boreal generalist fish which are expected to affect arctic marine food web structure and ecosystem functioning substantially. Here, we address structural changes at the food web level induced by poleward shifts via topological network analysis of highly resolved boreal and arctic food webs of the Barents Sea. We detected considerable differences in structural properties and link configuration between the boreal and the arctic food webs, the latter being more modular and less connected. We found that a main characteristic of the boreal fish moving poleward into the arctic region of the Barents Sea is high generalism, a property that increases connectance and reduces modularity in the arctic marine food web. Our results reveal that habitats form natural boundaries for food web modules, and that generalists play an important functional role in coupling pelagic and benthic modules. We posit that these habitat couplers have the potential to promote the transfer of energy and matter between habitats, but also the spread of pertubations, thereby changing arctic marine food web structure considerably with implications for ecosystem dynamics and functioning. PMID:26336179

  12. DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a

    Science.gov (United States)

    Walters, Kylie J.; Lech, Patrycja J.; Goh, Amanda M.; Wang, Qinghua; Howley, Peter M.

    2003-01-01

    The Rad23 family of proteins, including the human homologs hHR23a and hHR23b, stimulates nucleotide excision repair and has been shown to provide a novel link between proteasome-mediated protein degradation and DNA repair. In this work, we illustrate how the proteasomal subunit S5a regulates hHR23a protein structure. By using NMR spectroscopy, we have elucidated the structure and dynamic properties of the 40-kDa hHR23a protein and show it to contain four structured domains connected by flexible linker regions. In addition, we reveal that these domains interact in an intramolecular fashion, and by using residual dipolar coupling data in combination with chemical shift perturbation analysis, we present the hHR23a structure. By itself, hHR23a adopts a closed conformation defined by the interaction of an N-terminal ubiquitin-like domain with two ubiquitin-associated domains. Interestingly, binding of the proteasomal subunit S5a disrupts the hHR23a interdomain interactions and thereby causes it to adopt an opened conformation. PMID:14557549

  13. Climate change alters the structure of arctic marine food webs due to poleward shifts of boreal generalists.

    Science.gov (United States)

    Kortsch, Susanne; Primicerio, Raul; Fossheim, Maria; Dolgov, Andrey V; Aschan, Michaela

    2015-09-07

    Climate-driven poleward shifts, leading to changes in species composition and relative abundances, have been recently documented in the Arctic. Among the fastest moving species are boreal generalist fish which are expected to affect arctic marine food web structure and ecosystem functioning substantially. Here, we address structural changes at the food web level induced by poleward shifts via topological network analysis of highly resolved boreal and arctic food webs of the Barents Sea. We detected considerable differences in structural properties and link configuration between the boreal and the arctic food webs, the latter being more modular and less connected. We found that a main characteristic of the boreal fish moving poleward into the arctic region of the Barents Sea is high generalism, a property that increases connectance and reduces modularity in the arctic marine food web. Our results reveal that habitats form natural boundaries for food web modules, and that generalists play an important functional role in coupling pelagic and benthic modules. We posit that these habitat couplers have the potential to promote the transfer of energy and matter between habitats, but also the spread of pertubations, thereby changing arctic marine food web structure considerably with implications for ecosystem dynamics and functioning. © 2015 The Authors.

  14. Disconnect between alcohol-induced alterations in chromatin structure and gene transcription in a mouse embryonic stem cell model of exposure.

    Science.gov (United States)

    Veazey, Kylee J; Wang, Haiqing; Bedi, Yudhishtar S; Skiles, William M; Chang, Richard Cheng-An; Golding, Michael C

    2017-05-01

    Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program. To address this question, we examined the impact of ethanol exposure in mouse embryonic stem cells cultured under 2i conditions, where the transcriptional program is rigidly enforced through the use of small molecule inhibitors. We find that ethanol-induced changes in post-translational histone modifications are dose-dependent, unique to the chromatin modification under investigation, and that the extent and direction of the change differ between the period of exposure and the recovery phase. Similar to in vivo models, we find post-translational modifications affecting histone 3 lysine 9 are the most profoundly impacted, with the signature of exposure persisting long after alcohol has been removed. These changes in chromatin structure associate with dose-dependent alterations in the levels of transcripts encoding Dnmt1, Uhrf1, Tet1, Tet2, Tet3, and Polycomb complex members Eed and Ezh2. However, in this model, ethanol-induced changes to the chromatin template do not consistently associate with changes in gene transcription, impede the process of differentiation, or affect the acquisition of monoallelic patterns of expression for the imprinted gene Igf2R. These findings question the inferred universal relevance of epigenetic changes induced by drugs of abuse and suggest that changes

  15. Discriminating the drivers of edge effects on nest predation: forest edges reduce capture rates of ship rats (Rattus rattus), a globally invasive nest predator, by altering vegetation structure.

    Science.gov (United States)

    Ruffell, Jay; Didham, Raphael K; Barrett, Paul; Gorman, Nic; Pike, Rhonda; Hickey-Elliott, Andrée; Sievwright, Karin; Armstrong, Doug P

    2014-01-01

    Forest edges can strongly affect avian nest success by altering nest predation rates, but this relationship is inconsistent and context dependent. There is a need for researchers to improve the predictability of edge effects on nest predation rates by examining the mechanisms driving their occurrence and variability. In this study, we examined how the capture rates of ship rats, an invasive nest predator responsible for avian declines globally, varied with distance from the forest edge within forest fragments in a pastoral landscape in New Zealand. We hypothesised that forest edges would affect capture rates by altering vegetation structure within fragments, and that the strength of edge effects would depend on whether fragments were grazed by livestock. We measured vegetation structure and rat capture rates at 488 locations ranging from 0-212 m from the forest edge in 15 forest fragments, seven of which were grazed. Contrary to the vast majority of previous studies of edge effects on nest predation, ship rat capture rates increased with increasing distance from the forest edge. For grazed fragments, capture rates were estimated to be 78% lower at the forest edge than 118 m into the forest interior (the farthest distance for grazed fragments). This relationship was similar for ungrazed fragments, with capture rates estimated to be 51% lower at the forest edge than 118 m into the forest interior. A subsequent path analysis suggested that these 'reverse' edge effects were largely or entirely mediated by changes in vegetation structure, implying that edge effects on ship rats can be predicted from the response of vegetation structure to forest edges. We suggest the occurrence, strength, and direction of edge effects on nest predation rates may depend on edge-driven changes in local habitat when the dominant predator is primarily restricted to forest patches.

  16. Pulmonary Hypertension in Scleroderma

    Science.gov (United States)

    ... to improve exercise capacity, pulmonary artery pressure, and functional class in patients with PAH. Potential side effects include flushing, dyspepsia, visual changes, and nosebleeds. Tadalafil ...

  17. Pulmonary alveolar proteinosis

    Science.gov (United States)

    PAP; Alveolar proteinosis; Pulmonary alveolar phospholipoproteinosis; Alveolar lipoproteinosis phospholipidosis ... PAP is unknown. In others, it occurs with lung infection or an immune problem. It also can ...

  18. Pulmonary vasculitis: imaging features

    International Nuclear Information System (INIS)

    Seo, Joon Beom; Im, Jung Gi; Chung, Jin Wook; Goo, Jin Mo; Park, Jae Hyung; Yeon, Kyung Mo; Song, Jae Woo

    1999-01-01

    Vasculitis is defined as an inflammatory process involving blood vessels, and can lead to destruction of the vascular wall and ischemic damage to the organs supplied by these vessels. The lung is commonly affected. A number of attempts have been made to classify and organize pulmonary vasculitis, but because the clinical manifestations and pathologic features of the condition overlap considerably, these afforts have failed to achieve a consensus. We classified pulmonary vasculitis as belonging to either the angitiis-granulomatosis group, the diffuse pulmonary hemorrhage with capillaritis group, or 'other'. Characteristic radiographic and CT findings of the different types of pulmonary vasculitis are illustrated, with a brief discussion of the respective disease entities

  19. Neurogenic Pulmonary Edema.

    Science.gov (United States)

    Busl, Katharina M; Bleck, Thomas P

    2015-08-01

    Neurogenic pulmonary edema is an underrecognized and underdiagnosed form of pulmonary compromise that complicates acute neurologic illness and is not explained by cardiovascular or pulmonary pathology. This review aims to provide a concise overview on pathophysiology, epidemiology, clinical characteristics, impact on outcome and treatment of neurogenic pulmonary edema, and considerations for organ donation. Database searches and a review of the relevant medical literature. Selected studies included English-language articles concerning neurogenic pulmonary edema using the search terms "neurogenic" with "pulmonary oedema" or "pulmonary edema," "experimental neurogenic pulmonary edema," "donor brain death," and "donor lung injury." Selected studies were reviewed by both authors, and data extracted based on author consensus regarding relevance for this review. Existing evidence is organized to address: 1) pathophysiology, 2) epidemiology and association with different neurologic diseases, 3) clinical presentation, 4) impact on outcome, 5) treatment, and 6) implications for organ donation after brain death. Neurogenic pulmonary edema occurs as a complication of acute neurologic illness and may mimic acute lung injury of other etiology. Its presence is important to recognize in patients due to its impact on clinical course, prognosis, and treatment strategies.

  20. Radiological diagnosis of pulmonary edema in chronic renal failure

    International Nuclear Information System (INIS)

    Tret'yakov, A.E.

    1983-01-01

    Pulmonary edema has been revealed in 132 patients (51.6 %) during radiologic examination of 256 patients with chronic renal failure. The performance of anterio-posterior chest radiographs was in most cases necessary and quite sufficient for making diagnostic conclusions. Follow up study of patients with pulmonary edema and analysis of radiologic picture of the alterations permitted physicians to distinguish approximately 3 stages of the process development, which transit from one into another. Stage 1 involves early disorders and prodromes of pulmonary edema; Stage 2 interstitial lung edema; Stage 3 alveolar edema. The circulation enforcement of the upper lobar vessels has been the main feature of stage 1. Radiogramometry provided additional information for the pulmonary edema diagnosis. For instance, cardioradiometric data are useful for pulmonary edema diagnosis and evidence in favour of its close connection with heart disorders

  1. Diagnosis and treatment of pulmonary hypertension in infancy

    Science.gov (United States)

    Steinhorn, Robin H.

    2013-01-01

    Normal pulmonary vascular development in infancy requires maintenance of low pulmonary vascular resistance after birth, and is necessary for normal lung function and growth. The developing lung is subject to multiple genetic, pathological and/or environmental influences that can adversely affect lung adaptation, development, and growth, leading to pulmonary hypertension. New classifications of pulmonary hypertension are beginning to account for these diverse phenotypes, and or pulmonary hypertension in infants due to PPHN, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). The most effective pharmacotherapeutic strategies for infants with PPHN are directed at selective reduction of PVR, and take advantage of a rapidly advancing understanding of the altered signaling pathways in the remodeled vasculature. PMID:24083892

  2. [Pulmonary hypertension in hemodialysis patients: Prevalence and associated factors].

    Science.gov (United States)

    Reque, Javier; Quiroga, Borja; Ruiz, Caridad; Villaverde, Maria Teresa; Vega, Almudena; Abad, Soraya; Panizo, Nayara; López-Gómez, J Manuel

    2016-02-19

    Pulmonary hypertension (PH) is a progressive disorder that can be caused by several underlying conditions or an intrinsic alteration of the pulmonary vasculature. Chronic increased pressure in the pulmonary vasculature leads to changes in the architecture of the vessels that can perpetuate PH and produce right ventricular dysfunction. These structural and functional alterations can decrease survival and quality of life of patients on hemodialysis; however, there is a lack of evidence about this problem in this population. The aim of this study is to establish the prevalence of PH in patients on hemodialysis and its association with specific factors related to this patient population. We included 202 prevalent patients on hemodialysis for at least 6 months and who were clinically stable. We collected demographic data, routine laboratory parameters and data of 2D Doppler-echocardiography. PH was defined as a systolic pulmonary artery pressure (SPAP) estimated by Doppler ultrasound above 35mmHg. Hydration status was assessed by determining the plasma concentration of N-terminal pro brain natriuretic peptide (Nt-proBNP). PH prevalence was 37.1% (75 patients). The average SPAP in the entire study population was 32±12mmHg and in the group with PH it was 45±11mmHg. We found a direct and statistically significant correlation between the presence of PH and age (P=.001), time on renal replacement therapy (P=.04), the presence of systolic dysfunction (P=.007), diastolic dysfunction (P= 01), mitral valve disease (P=.01) and double mitral and aortic disease (P=.007). Volume overload was closely associated with PH, as demonstrated by the correlation between the SPAP and Nt-proBNP levels (P=.001). We conclude that prevalence of PH in hemodialysis patients is high. And one of the most important associated factors is volume overload. More studies are needed to establish the impact of PH on morbidity and mortality of patients and to assess whether a better volume control improves

  3. Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders.

    Science.gov (United States)

    Perez, David L; Matin, Nassim; Barsky, Arthur; Costumero-Ramos, Victor; Makaretz, Sara J; Young, Sigrid S; Sepulcre, Jorge; LaFrance, W Curt; Keshavan, Matcheri S; Dickerson, Bradford C

    2017-06-01

    Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas. This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects. Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume. This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017

  4. Athermal alterations in the structure in the canalicular membrane and ATPase activity induced by thermal levels of microwave radiation

    International Nuclear Information System (INIS)

    Phelan, A.M.; Neubauer, C.F.; Timm, R.; Neirenberg, J.; Lange, D.G.

    1994-01-01

    Sprague-Dawley rats (200-250 g) were exposed 30 min/day for 4 days to thermogenic levels (rectal temperature increase of 2.2 degrees C) of microwave radiation [2.45 GHz, 80 mW/cm 2 , continuous-wave mode (CW)] or to a radiant heat source resulting in an equivalent increase in body temperature of 2.2 degrees C. On the fifth day the animals were sacrificed and their livers removed. The canalicular membranes were isolated and evaluated for adenosinetriphosphatase (ATPase) activity, total fatty acid composition and membrane fluidity characteristics. Mg ++ -ATPase activity (V max ) decreased by 48.5% in the group exposed to microwave radiation, with no significant change in the group exposed to radiant heat. The decrease in Mg ++ -ATPase was partially compensated by a concomitant increase in Na + /K + -ATPase activity (170% increase in V max over control) in animals exposed to microwave radiation, while no change occurred in the group exposed to radiant heat. This alteration in ATPase activity in the group exposed to microwave radiation is associated with a large decrease in the ratio of saturated to unsaturated fatty acids. Conversely, the group exposed to radiant heat had an increase in the ratio of saturated to unsaturated fatty acids. The most dramatic changes were found in the levels of arachidonic acid. Finally, the electron paramagnetic resonance (EPR) spin label technique used to measure the fluidity of the canalicular membranes of the animals in the three groups (sham, microwave radiation and radiant heat) indicated that the results were different in the three groups, reflecting the changes found in their fatty acid composition. The physiological response to open-quotes equivalentclose quotes thermal loads in rats is expressed differently for different types of energy sources. Possible mechanisms producing these divergent thermogenic responses are discussed. 34 refs., 3 figs., 2 tabs

  5. 3-Deoxyglucosone: a potential glycating agent accountable for structural alteration in H3 histone protein through generation of different AGEs.

    Directory of Open Access Journals (Sweden)

    Jalaluddin M Ashraf

    Full Text Available Advanced glycation end-products (AGEs are heterogeneous group of compounds, known to be implicated in diabetic complications. One of the consequences of the Maillard reaction is attributed to the production of reactive intermediate products such as α-oxoaldehydes. 3-deoxyglucosone (3-DG, an α-oxoaldehyde has been found to be involved in accelerating vascular damage during diabetes. In the present study, calf thymus histone H3 was treated with 3-deoxyglucosone to investigate the generation of AGEs (Nε-carboxymethyllysine, pentosidine, by examining the degree of side chain modifications and formation of different intermediates and employing various physicochemical techniques. The results clearly indicate the formation of AGEs and structural changes upon glycation of H3 by 3-deoxyglucosone, which may hamper the normal functioning of H3 histone, that may compromise the veracity of chromatin structures and function in secondary complications of diabetes.

  6. Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

    Science.gov (United States)

    Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

    2016-11-01

    Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (Pbulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

  7. STRUCTURAL AND CONNECTOMIC NEUROIMAGING FOR THE PERSONALIZED STUDY OF LONGITUDINAL ALTERATIONS IN CORTICAL SHAPE, THICKNESS AND CONNECTIVITY AFTER TRAUMATIC BRAIN INJURY

    Science.gov (United States)

    Irimia, A.; Goh, S.-Y. M.; Torgerson, C. M.; Vespa, P. M.; Van Horn, J. D.

    2014-01-01

    The integration of longitudinal brain structure analysis with neurointensive care strategies continues to be a substantial difficulty facing the traumatic brain injury (TBI) research community. For patient-tailored case analysis, it remains challenging to establish how lesion profile modulates longitudinal changes in cortical structure and connectivity, as well as how these changes lead to behavioral, cognitive and neural dysfunction. Additionally, despite the clinical potential of morphometric and connectomic studies, few analytic tools are available for their study in TBI. Here we review the state of the art in structural and connectomic neuroimaging for the study of TBI and illustrate a set of recently-developed, patient-tailored approaches for the study of TBI-related brain atrophy and alterations in morphometry as well as inter-regional connectivity. The ability of such techniques to quantify how injury modulates longitudinal changes in cortical shape, structure and circuitry is highlighted. Quantitative approaches such as these can be used to assess and monitor the clinical condition and evolution of TBI victims, and can have substantial translational impact, especially when used in conjunction with measures of neuropsychological function. PMID:24844173

  8. Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

    Science.gov (United States)

    Dechow, Paul C.; Wang, Qian; Peterson, Jill

    2011-01-01

    Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which

  9. Are changes in the phytoplankton community structure altering the flux of CO2 in regions of the North Atlantic?

    Science.gov (United States)

    Ostle, C.; Landschutzer, P.; Johnson, M.; Schuster, U.; Watson, A. J.; Edwards, M.; Robinson, C.

    2016-02-01

    The North Atlantic Ocean is a globally important sink of carbon dioxide (CO2). However, the strength of the sink varies temporally and regionally. This study uses a neural network method to map the surface ocean pCO2 (partial pressure of CO2) and flux of CO2from the atmosphere to the ocean alongside measurements of plankton abundance collected from the Continuous Plankton Recorder (CPR) survey to determine the relationship between regional changes in phytoplankton community structure and regional differences in carbon flux. Despite increasing sea surface temperatures, the Grand Banks of Newfoundland show a decrease in sea surface pCO2 of -2 µatm yr-1 from 1993 to 2011. The carbon flux in the North Sea is variable over the same period. This is in contrast to most of the open ocean within the North Atlantic, where increases in sea surface pCO2 follow the trend of increasing CO2 in the atmosphere, i.e. the flux or sink remains constant. The increasing CO2 sink in the Grand Banks of Newfoundland and the variable sink in the North Sea correlate with changes in phytoplankton community composition. This study investigates the biogeochemical and oceanographic mechanisms potentially linking increasing sea surface temperature, changes in phytoplankton community structure and the changing carbon sink in these two important regions of the Atlantic Ocean. The use of volunteer ships to concurrently collect these datasets demonstrates the potential to investigate relationships between plankton community structure and carbon flux in a cost-effective way. These results not only have implications for plankton-dynamic biogeochemical models, but also likely influence carbon export, as different phytoplankton communities have different carbon export efficiencies. Extending and maintaining such datasets is critical to improving our understanding of and monitoring carbon cycling in the surface ocean and improving climate model accuracy.

  10. The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

    Science.gov (United States)

    Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

    2016-01-01

    The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

  11. Bamboo thickets alter the demographic structure of Euterpe edulis population: A keystone, threatened palm species of the Atlantic forest

    Science.gov (United States)

    Rother, Débora Cristina; Rodrigues, Ricardo Ribeiro; Pizo, Marco Aurélio

    2016-01-01

    The rapid spread of bamboos can strongly affect forest structure by interfering plant regeneration and reducing local biodiversity. Considering that bamboos exert a negative influence on the plant community, our main goal was to investigate how this influence manifests at the population level. We compared the demographic structure of the threatened palm Euterpe edulis between bamboo and non-bamboo dominated patches within the Atlantic forest. In the study site, the native bamboo Guadua tagoara has created a marked patchiness and heterogeneity in the vegetation. Plots were set up randomly in bamboo and non-bamboo patches and the heights of all E. edulis individuals were measured. Data from canopy openness and litter depth were collected for both patches. Greater number of E. edulis was recorded in bamboo patches. However, frequency distribution of the height classes differed between patches revealing a predominance of seedling and sapling I classes in bamboo patches, in comparison to a more evenly distribution of height classes in non-bamboo patches. The canopy in bamboo patches was more open and the litter depth was thicker. Our analyses evidenced G. tagoara is functioning as a demographic bottleneck of natural population of E. edulis by arresting its later stages of regeneration and in high densities that bamboos may limit recruitment of this palm species.

  12. Structural brain alterations in bipolar disorder II: a combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study.

    Science.gov (United States)

    Ambrosi, Elisa; Rossi-Espagnet, Maria Camilla; Kotzalidis, Georgios D; Comparelli, Anna; Del Casale, Antonio; Carducci, Filippo; Romano, Andrea; Manfredi, Giovanni; Tatarelli, Roberto; Bozzao, Alessandro; Girardi, Paolo

    2013-09-05

    Brain structural changes have been described in bipolar disorder (BP), but usually studies focused on both I and II subtypes indiscriminately and investigated changes in either brain volume or white matter (WM) integrity. We used combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to track changes in the grey matter (GM) and WM in the brains of patients affected by BPII, as compared to healthy controls. Using VBM and DTI, we scanned 20 DSM-IV-TR BPII patients in their euthymic phase and 21 healthy, age- and gender-matched volunteers with no psychiatric history. VBM showed decreases in GM of BPII patients, compared to controls, which were diffuse in nature and most prominent in the right middle frontal gyrus and in the right superior temporal gurus. DTI showed significant and widespread FA reduction in BPII patients in all major WM tracts, including cortico-cortical association tracts. The small sample size limits the generalisability of our findings. Reduced GM volumes and WM integrity changes in BPII patients are not prominent like those previously reported in bipolar disorder type-I and involve cortical structures and their related association tracts. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Altered hippocampal arteriole structure and function in a rat model of preeclampsia: Potential role in impaired seizure-induced hyperemia.

    Science.gov (United States)

    Johnson, Abbie C; Cipolla, Marilyn J

    2017-08-01

    We investigated the effect of experimental preeclampsia on hyperemia during seizure in the hippocampus and vascular function and structure of hippocampal arterioles using Sprague Dawley rats (n = 14/group) that were nonpregnant, pregnant (d20), or had experimental preeclampsia (induced by a high cholesterol diet d7-20). Hyperemia was measured via hydrogen clearance basally and during pentylenetetrazol-induced seizure (40-130 mg/kg i.v.). Reactivity of isolated and pressurized hippocampal arterioles to KCl, nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester and the nitric oxide donor sodium nitroprusside were investigated. Capillary density was quantified via immunohistochemistry. Cerebral blood flow increased during seizure vs. baseline in pregnant (118 ± 14 vs. 87 ± 9 mL/100 g/min; p  0.05), suggesting impaired seizure-induced hyperemia in preeclampsia. Hippocampal arterioles from preeclamptic rats had less basal tone, and dilated less to 15 mM KCl (9 ± 8%) vs. pregnant (61 ± 27%) and nonpregnant rats (20 ± 11%). L-NAME had no effect on hippocampal arterioles in any group, but dilation to sodium nitroprusside was similar. Structurally, hippocampal arterioles from preeclamptic rats underwent inward hypotrophic remodeling and capillary rarefaction. Impaired seizure-induced hyperemia, vascular dysfunction, and limited vasodilatory reserve of hippocampal arterioles could potentiate hippocampal injury in preeclampsia especially during eclampsia.

  14. Inhibition of methane and natural gas hydrate formation by altering the structure of water with amino acids

    Science.gov (United States)

    Sa, Jeong-Hoon; Kwak, Gye-Hoon; Han, Kunwoo; Ahn, Docheon; Cho, Seong Jun; Lee, Ju Dong; Lee, Kun-Hong

    2016-08-01

    Natural gas hydrates are solid hydrogen-bonded water crystals containing small molecular gases. The amount of natural gas stored as hydrates in permafrost and ocean sediments is twice that of all other fossil fuels combined. However, hydrate blockages also hinder oil/gas pipeline transportation, and, despite their huge potential as energy sources, our insufficient understanding of hydrates has limited their extraction. Here, we report how the presence of amino acids in water induces changes in its structure and thus interrupts the formation of methane and natural gas hydrates. The perturbation of the structure of water by amino acids and the resulting selective inhibition of hydrate cage formation were observed directly. A strong correlation was found between the inhibition efficiencies of amino acids and their physicochemical properties, which demonstrates the importance of their direct interactions with water and the resulting dissolution environment. The inhibition of methane and natural gas hydrate formation by amino acids has the potential to be highly beneficial in practical applications such as hydrate exploitation, oil/gas transportation, and flow assurance. Further, the interactions between amino acids and water are essential to the equilibria and dynamics of many physical, chemical, biological, and environmental processes.

  15. Reach-scale stream restoration in agricultural streams of southern Minnesota alters structural and functional responses of macroinvertebrates

    Science.gov (United States)

    Dolph, Christine L.; Eggert, Susan L.; Magner, Joe; Ferrington, Leonard C.; Vondracek, Bruce C.

    2015-01-01

    Recent studies suggest that stream restoration at the reach scale may not increase stream biodiversity, raising concerns about the utility of this conservation practice. We examined whether reach-scale restoration in disturbed agricultural streams was associated with changes in macroinvertebrate community structure (total macroinvertebrate taxon richness, total macroinvertebrate density, Ephemeroptera, Plecoptera, Trichoptera [EPT] taxon richness, % abundance of EPT taxa) or secondary production (macroinvertebrate biomass over time). We collected macroinvertebrate samples over the course of 1 y from restored and unrestored reaches of 3 streams in southern Minnesota and used generalized least-square (GLS) models to assess whether measures of community structure were related to reach type, stream site, or sampling month. After accounting for effects of stream site and time, we found no significant difference in total taxon richness or % abundance of EPT taxa between restored and unrestored reaches. However, the number of EPT taxa and macroinvertebrate density were significantly higher in restored than in unrestored reaches. We compared secondary production estimates among study reaches based on 95th-percentile confidence intervals generated via bootstrapping. In each study stream, secondary production was significantly (2–3×) higher in the restored than in the unrestored reach. Higher productivity in the restored reaches was largely a result of the disproportionate success of a few dominant, tolerant taxa. Our findings suggest that reach-scale restoration may have ecological effects that are not detected by measures of total taxon richness alone.

  16. Cardio-Pulmonary Response to Shock.

    Science.gov (United States)

    1981-02-01

    cardiopulnonary abnormalities of pulmonary embolism and in reversing lethal endotoxemia . Towever, PG12 was without benefit in treating acid...vessel i0 - -- - 5. PGI2 reversal of lethal endotoxemia in dogs 6. Thromboxane response to PGI2 and aspirin treatment in lethal endotoxemia D. Platelet...unstable hemodynamics during lung perfusion (5) Pressure breathing alters prostaglandin (PG) metabolism which may in part be responsible for the

  17. A hypertension-associated mitochondrial DNA mutation introduces an m1G37 modification into tRNAMet, altering its structure and function.

    Science.gov (United States)

    Zhou, Mi; Xue, Ling; Chen, Yaru; Li, Haiying; He, Qiufen; Wang, Bibin; Meng, Feilong; Wang, Meng; Guan, Min-Xin

    2018-01-26

    Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A→G mutation in mitochondrial tRNA Met The m.4435A→G mutation affected a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m.4435A→G mutation introduced an m 1 G37 modification of tRNA Met , altering its structure and function. Primer extension and methylation activity assays indeed confirmed that the m.4435A→G mutation created a tRNA methyltransferase 5 (TRMT5)-catalyzed m 1 G37 modification of tRNA Met We found that this mutation altered the tRNA Met structure, indicated by an increased melting temperature and electrophoretic mobility of the mutated tRNA compared with the wildtype molecule. We demonstrated that cybrid cell lines carrying the m.4435A→G mutation exhibited significantly decreased efficiency in aminoacylation and steady-state levels of tRNA Met , as compared with those of control cybrids. The aberrant tRNA Met metabolism resulted in variable decreases in mitochondrial DNA (mtDNA)-encoded polypeptides in the mutant cybrids. Furthermore, we found that the m.4435A→G mutation caused respiratory deficiency, markedly diminished mitochondrial ATP levels and membrane potential, and increased the production of reactive oxygen species in mutant cybrids. These results demonstrated that an aberrant m 1 G37 modification of mitochondrial tRNA Met affected the structure and function of its tRNA and consequently altered mitochondrial function. Our findings provide critical insights into the pathophysiology of maternally inherited hypertension, which is manifested by the deficient tRNA nucleotide modification. © 2018 by The American Society for Biochemistry and

  18. pulmonary tuberculosis, jimma hospital

    African Journals Online (AJOL)

    and National Tuberculosis and Leprosy Control Program manual. RESULTS: A total of 112 extra pulmonary ... Key words: Clinical audit; extra pulmonary Tuberculosis; National Tuberculosis and. Leprosy Control manual. "Addis Ababa ..... intern influence drug regimen selection. Compliance to the 1997 NTLCP inanual is.

  19. Bilateral meandering pulmonary veins

    Energy Technology Data Exchange (ETDEWEB)

    Thupili, Chakradhar R.; Udayasankar, Unni [Pediatric Imaging, Imaging Institute Cleveland Clinic, Cleveland, OH (United States); Renapurkar, Rahul [Imaging Institute Cleveland Clinic, Thoracic Imaging, L10, Cleveland, OH (United States)

    2015-06-15

    Meandering pulmonary veins is a rare clinical entity that can be mistaken for more complex congenital syndromes such as hypogenetic lung syndrome. We report imaging findings in a rare incidentally detected case of bilateral meandering pulmonary veins. We briefly discuss the role of imaging in diagnosing this condition, with particular emphasis on contrast-enhanced CT. (orig.)

  20. The role of dual-energy computed tomography in the assessment of pulmonary function

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Jeon [Department of Radiology, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do 431-796 (Korea, Republic of); Hoffman, Eric A. [Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, 200 Hawkins Dr, CC 701 GH, Iowa City, IA 52241 (United States); Lee, Chang Hyun; Goo, Jin Mo [Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of); Levin, David L. [Department of Radiology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905 (United States); Kauczor, Hans-Ulrich [Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Seo, Joon Beom, E-mail: seojb@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap 2-dong, Songpa-ku, Seoul, 05505 (Korea, Republic of)

    2017-01-15

    Highlights: • The dual-energy CT technique enables the differentiation of contrast materials with material decomposition algorithm. • Pulmonary functional information can be evaluated using dual-energy CT with anatomic CT information, simultaneously. • Pulmonary functional information from dual-energy CT can improve diagnosis and severity assessment of diseases. - Abstract: The assessment of pulmonary function, including ventilation and perfusion status, is important in addition to the evaluation of structural changes of the lung parenchyma in various pulmonary diseases. The dual-energy computed tomography (DECT) technique can provide the pulmonary functional information and high resolution anatomic information simultaneously. The application of DECT for the evaluation of pulmonary function has been investigated in various pulmonary diseases, such as pulmonary embolism, asthma and chronic obstructive lung disease and so on. In this review article, we will present principles and technical aspects of DECT, along with clinical applications for the assessment pulmonary function in various lung diseases.

  1. Ab initio van der waals interactions in simulations of water alter structure from mainly tetrahedral to high-density-like

    DEFF Research Database (Denmark)

    Møgelhøj, Andreas; Kelkkanen, Kari André; Wikfeldt, K Thor

    2011-01-01

    The structure of liquid water at ambient conditions is studied in ab initio molecular dynamics simulations in the NVE ensemble using van der Waals (vdW) density-functional theory, i.e., using the new exchange-correlation functionals optPBE-vdW and vdW-DF2, where the latter has softer nonlocal...... protocol could cause the deviation. An O-O PCF consisting of a linear combination of 70% from vdW-DF2 and 30% from low-density liquid water, as extrapolated from experiments, reproduces near-quantitatively the experimental O-O PCF for ambient water. This suggests the possibility that the new functionals...... shows some resemblance with experiment for high-density water ( Soper , A. K. and Ricci , M. A. Phys. Rev. Lett. 2000 , 84 , 2881 ), but not directly with experiment for ambient water. Considering the accuracy of the new functionals for interaction energies, we investigate whether the simulation...

  2. Altering F-Actin Structure of C17.2 Cells using Single-Walled Carbon Nanotubes

    Science.gov (United States)

    Magers, Jay; Gillette, Nathan L. D.; Rotkin, Slava V.; Jedlicka, Sabrina; Pirbhai, Massooma; Lehigh Univesity Collaboration; Susquehanna University Collaboration

    Advancements in nanotechnology have become fundamental to the delivery of drugs to treat various diseases. One such advancement is that of carbon nanotubes and their possible implications on drug delivery. Single-walled carbon nanotubes (SWCNTs) have great potential in the biomedical field as a means to deliver materials such as drugs and genes into the human body due to their size and chemistry. However, the effects of the nanotubes on cells they interact with are still unknown. Previous studies have shown that a low dosage of SWCNTs can affect differentiation of C17.2 neural stem cells. In this experiment, we investigate how the tubes affect the structure of the cells. Specifically, we determined the impact on the cell by examining the actin filament length, protrusions along the edge of the cells, and actin distribution. Presenter/Author 1.

  3. T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

    Science.gov (United States)

    Beausang, John F; Wheeler, Amanda J; Chan, Natalie H; Hanft, Violet R; Dirbas, Frederick M; Jeffrey, Stefanie S; Quake, Stephen R

    2017-11-28

    Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment. Copyright © 2017 the Author(s). Published by PNAS.

  4. Altering the Structure of Carbohydrate Storage Granules in the Cyanobacterium Synechocystis sp. Strain PCC 6803 through Branching-Enzyme Truncations

    Science.gov (United States)

    Welkie, David G.; Lee, Byung-Hoo

    2015-01-01

    ABSTRACT Carbohydrate storage is an important element of metabolism in cyanobacteria and in the chloroplasts of plants. Understanding how to manipulate the metabolism and storage of carbohydrate is also an important factor toward harnessing cyanobacteria for energy production. While most cyanobacteria produce glycogen, some have been found to accumulate polysaccharides in the form of water-insoluble α-glucan similar to amylopectin. Notably, this alternative form, termed “semi-amylopectin,” forms in cyanobacterial species harboring three branching-enzyme (BE) homologs, designated BE1, BE2, and BE3. In this study, mutagenesis of the branching genes found in Synechocystis sp. strain PCC 6803 was performed in order to characterize their possible impact on polysaccharide storage granule morphology. N-terminal truncations were made to the native BE gene of Synechocystis sp. PCC 6803. In addition, one of the two native debranching enzyme genes was replaced with a heterologous debranching enzyme gene from a semi-amylopectin-forming strain. Growth and glycogen content of mutant strains did not significantly differ from those of the wild type, and ultrastructure analysis revealed only slight changes to granule morphology. However, analysis of chain length distribution by anion-exchange chromatography revealed modest changes to the branched-chain length profile. The resulting glycogen shared structure characteristics similar to that of granules isolated from semi-amylopectin-producing strains. IMPORTANCE This study is the first to investigate the impact of branching-enzyme truncations on the structure of storage carbohydrates in cyanobacteria. The results of this study are an important contribution toward understanding the relationship between the enzymatic repertoire of a cyanobacterial species and the morphology of its storage carbohydrates. PMID:26668264

  5. A Voxel-Based Morphometry Study Reveals Local Brain Structural Alterations associated With Ambient Fine Particles in older women

    Directory of Open Access Journals (Sweden)

    Ramon Casanova

    2016-10-01

    Full Text Available Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters <2.5µm has been linked with cognitive deficits in older adults. Using fine-grained voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure.Methods: Brain MRI data were obtained from 1,365 women (aged 71-89 in the Women’s Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space. Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM and white matter (WM maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked WM decreased volumes to PM2.5 air pollution, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.

  6. Pediatric postprimary pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Shewchuk, Jason R.; Reed, Martin H.

    2002-01-01

    Heading AbstractBackground. Postprimary pulmonary tuberculosis (TB) is not commonly seen in children.Objective. The purpose of this study was to determine the radiographic findings and patient characteristics of pediatric postprimary pulmonary TB.Materials and methods. We reviewed the clinical charts and chest radiographs in six patients.Results. The radiographic findings of pediatric postprimary pulmonary TB include upper-lobe consolidation and cavitation, multifocal ill-defined airspace opacities, evidence of prior pulmonary TB, and apical pleural thickening. Pleural effusions and lymphadenopathy are not commonly present. Although postprimary disease typically does not affect young children, five of the children in this series were less than ten years of age at the time of presentation.Conclusion The possibility of postprimary TB should be considered in pediatric patients at risk for this disease who present with upper-lobe pulmonary consolidation and cavitation. These patients are highly infectious and early recognition and treatment can limit transmission of TB. (orig.)

  7. Nutrition Therapy in Elderly with Chronic Obstructive Pulmonary Disease (COPD

    Directory of Open Access Journals (Sweden)

    Minidian Fasitasari

    2013-06-01

    Full Text Available Nutrition is an important health element for elderly people and influence aging process. Malnutrition prevalence is increasing in this population. Chronic Obstructive Pulmonary Disease (COPD is one of the chronic diseases in elderly that is related to malnutrition. The association between malnutrition and pulmonary disease (including COPD has been known for a long time. Malnutrition has negative impacts on pulmonary structure, elasticity, and function, strength and endurance of respiratory muscles, pulmonary immunity defense mechanism, and breath control. Inversely, pulmonary disease (including COPD will increase energy need and may reduce dietary intake. Nutrition intervention in COPD patient is intended for regulating anorexia, improving pulmonary function, and controlling weight loss. Nutrient requirements will be calculated according to the results of nutrition assessment. This article will discuss about nutrition therapy in elderly with COPD. It describes respiratory system in aging, association COPD and nutrition, and nutrition assessment, as well as nutrition intervention in elderly people with COPD.

  8. Retrograde pulmonary embolectomy in massive pulmonary embolism.

    Science.gov (United States)

    Zarrabi, Khalil; Yarmohammadi, Hooman; Ostovan, Mohammad Ali

    2005-12-01

    The purpose of this study was introduction and evaluation of efficacy and safety of retrograde thromboembolectomy in acute massive pulmonary emboli. The method is described in a 56-year-old woman with acute massive pulmonary thromboemboli. Postoperative course was uneventful. The described surgical technique is not a panacea and definitely not the whole answer, but is a big part of the solution and may be accompanied with less adverse effects. Additionally, there is a need of being reviewed further in large experimental studies and measurements before it could be used safely as a new technique.

  9. Optical techniques in pulmonary medicine. SPIE photonics West.

    Science.gov (United States)

    Suter, Melissa J; Lam, Stephen; Brenner, Matthew

    2012-04-01

    There is ongoing interest in the emerging field of pulmonary photonic-based diagnostics. Potential clinical need areas that are being actively investigated at this time include airway and peripheral lung cancer diagnostics, pulmonary parenchymal and interstitial disorders, alveolar structure function, inhalation injury, ciliary function analysis, asthma and obstructive lung diseases.

  10. 3D pulmonary nodules detection using fast marching segmentation ...

    African Journals Online (AJOL)

    This paper proposes an automated computer aided diagnosis system for detection of pulmonary nodules based on three dimensional (3D) structures. Lung ... The proposed detection methodology can give the accuracy of 92%. Keywords: lung cancer; pulmonary nodule; fast marching; 3D features; random forest classifier.

  11. Mechanical valves in the pulmonary position : An international retrospective analysis

    NARCIS (Netherlands)

    Pragt, Hanna; van Melle, Joost P.; Javadikasgari, Hoda; Seo, Dong Man; Stulak, John M.; Knez, Igor; Hoerer, Juergen; Munoz-Guijosa, Christian; Dehaki, Mahyar G.; Shin, Hong Ju; Dearani, Joseph A.; Dehaki, Maziar G.; Pieper, Petronella G.; Eulenburg, Christine; Dos, Laura; Ebels, Tjark

    2017-01-01

    Objective: Life expectancy of patients with congenital heart disease has improved over the past decades, increasing the need for a durable pulmonary prosthetic valve. Biological valves in various forms have become the valve of choice for pulmonary valve replacement (PVR), but structural valve

  12. Long-term carbon exclusion alters soil microbial function but not community structure across forests of contrasting productivity

    Science.gov (United States)

    Hart, S. C.; Dove, N. C.; Stark, J.

    2017-12-01

    While it is well-documented that distinct heterotrophic microbial communities emerge under different conditions of carbon (C) availability, the response of soil microbial communities and their function to long-term conditions of C exclusion in situ has yet to be investigated. We evaluated the role of C in controlling soil microbial communities and function by experimentally excluding plant C inputs for nine years at four forest sites along a productivity gradient in Oregon, USA. Carbon exclusion treatments were implemented by root trenching to a depth of 30 cm using 25-cm diameter steel pipe, and minimizing aboveground inputs as plant litter by covering the pipe with a 1-mm mesh screen. After nine years, we measured rates of gross and net nitrogen (N) transformations and microbial respiration in situ in the upper 15-cm of mineral soil in both C excluded plots and undisturbed control soils. We measured the soil total C and N concentration and potential extracellular enzyme activities. We used phospholipid fatty acid (PLFA) analysis to determine potential changes in the microbial community structure. Nine years of C exclusion reduced soil total C by about 20%, except at the highest productivity site where no statistically significant change was observed. Although PLFA community structure and microbial C were unchanged, microbial respiration was reduced by 15-45% at all sites. Similarly, specific extracellular enzyme activities for all enzymes increased at these sites with C exclusion, suggesting that the microbial communities were substrate-limited. Although gross N mineralization decreased under C exclusion, decreases in gross N immobilization were greater, resulting in increased net N mineralization rates in all but the lowest productivity site. Furthermore, C exclusion only increased net nitrification in the highest productivity site. Although these field-based results are largely consistent with previous laboratory studies indicating a strong coupling between C

  13. Exposure of tropoelastin to peroxynitrous acid gives high yields of nitrated tyrosine residues, di-tyrosine cross-links and altered protein structure and function

    DEFF Research Database (Denmark)

    Degendorfer, Georg; Chuang, Christine Yu-Nung; Mariotti, Michele

    2018-01-01

    Elastin is an abundant extracellular matrix protein in elastic tissues, including the lungs, skin and arteries, and comprises 30–57% of the aorta by dry mass. The monomeric precursor, tropoelastin (TE), undergoes complex processing during elastogenesis to form mature elastic fibres. Peroxynitrous......-damaged extracellular matrix implicated in lesion rupture. We demonstrate that TE is highly sensitive to ONOOH, with this resulting in extensive dimerization, fragmentation and nitration of Tyr residues to give 3-nitrotyrosine (3-nitroTyr). This occurs with equimolar or greater levels of oxidant and increases in a dose...... with lipid deposits. These data suggest that exposure of TE to ONOOH gives marked chemical and structural changes to TE and altered matrix assembly, and that such damage accumulates in human arterial tissue during the development of atherosclerosis....

  14. Structural alteration of industry of region as pre-condition of steady development of national economy (on the example of the Dnepropetrovsk area

    Directory of Open Access Journals (Sweden)

    V. E. Vlasiuk

    2014-02-01

    Full Text Available An economic analysis is conducted in the production sphere of the Dnepropetrovsk area in a period development and in the process of transformation production to the sector of the national economic system. In particular, an analysis of the actual state of socio ­economic development of the Dnipropetrovsk region in the late XX century and its current state in order to find trends change attributes of manifestation and impact on living standards . The analysis of individual industries Dnipropetrovsk region. It is shown that the basis of the regional industry ­ metallurgy. Comparative analysis of the sectoral structure of industrial production Dnipropetrovsk Oblast major types of products that characterize its economy in 1997 and 2012. This analysis revealed the changes in the structural transformation of the regional industry . The basic indicators of socio­ economic development of the Dnipropetrovsk region. In particular , it was found that the dynamics of socio ­economic development of the region by major figures exceeded the average values in Ukraine , and the main results of 2011 was a steady growth in key sectors of the Dnipropetrovsk region. Were clarified problems of the region’s economy and its future prospects . The factors of forming of regional economic policy and principles of structural alteration of industry are considered.

  15. Structural and molecular alterations of primary afferent fibres in the spinal dorsal horn in vincristine-induced neuropathy in rat.

    Science.gov (United States)

    Thibault, Karine; Rivals, Isabelle; M'Dahoma, Saïd; Dubacq, Sophie; Pezet, Sophie; Calvino, Bernard

    2013-11-01

    Vincristine is one of the most common anti-cancer drug therapies administered for the treatment of many types of cancer. Its dose-limiting side effect is the emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. This study sought to understand the mechanisms underlying the development of neuropathic pain by vincristine-induced neurotoxicity. We focused on signs of functional changes and revealed that deep layers of the spinal cord (III-IV) experience increased neuronal activity both in the absence of peripheral stimulation and, as a result of tactile mechanical stimulations. These laminae and superficial laminae I-II were also subject to structural changes as evidenced by an increase in immunoreactivity of Piccolo, a marker of active presynaptic elements. Further investigations performed, using DNA microarray technology, describe a large number of genes differentially expressed in dorsal root ganglions and in the spinal dorsal horn after vincristine treatment. Our study describes an important list of genes differentially regulated by vincristine treatment that will be useful for future studies and brings forward evidence for molecular and anatomical modifications of large diameter sensory neurons terminating in deep dorsal horn laminae, which could participate in the development of tactile allodynia.

  16. Persistent expression of activated notch in the developing hypothalamus affects survival of pituitary progenitors and alters pituitary structure.

    Science.gov (United States)

    Aujla, Paven K; Bogdanovic, Vedran; Naratadam, George T; Raetzman, Lori T

    2015-08-01

    As the pituitary gland develops, signals from the hypothalamus are necessary for pituitary induction and expansion. Little is known about the control of cues that regulate early signaling between the two structures. Ligands and receptors of the Notch signaling pathway are found in both the hypothalamus and Rathke's pouch. The downstream Notch effector gene Hes1 is required for proper pituitary formation; however, these effects could be due to the action of Hes1 in the hypothalamus, Rathke's pouch, or both. To determine the contribution of hypothalamic Notch signaling to pituitary organogenesis, we used mice with loss and gain of Notch function within the developing hypothalamus. We demonstrate that loss of Notch signaling by conditional deletion of Rbpj in the hypothalamus does not affect expression of Hes1 within the posterior hypothalamus or expression of Hes5. In contrast, expression of activated Notch within the hypothalamus results in ectopic Hes5 expression and increased Hes1 expression, which is sufficient to disrupt pituitary development and postnatal expansion. Taken together, our results indicate that Rbpj-dependent Notch signaling within the developing hypothalamus is not necessary for pituitary development, but persistent Notch signaling and ectopic Hes5 expression in hypothalamic progenitors affects pituitary induction and expansion. © 2015 Wiley Periodicals, Inc.

  17. Local structures of mesoporous bioactive glasses and their surface alterations in vitro: inferences from solid-state nuclear magnetic resonance

    Science.gov (United States)

    Gunawidjaja, Philips N.; Mathew, Renny; Lo, Andy Y. H.; Izquierdo-Barba, Isabel; García, Ana; Arcos, Daniel; Mattias Edén, María Vallet-Regí

    2012-01-01

    We review the benefits of using 29Si and 1H magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy for probing the local structures of both bulk and surface portions of mesoporous bioactive glasses (MBGs) of the CaO–SiO2−(P2O5) system. These mesoporous materials exhibit an ordered pore arrangement, and are promising candidates for improved bone and tooth implants. We discuss experimental MAS NMR results from three MBGs displaying different Ca, Si and P contents: the 29Si NMR spectra were recorded either directly by employing radio-frequency pulses to 29Si, or by magnetization transfers from neighbouring protons using cross polarization, thereby providing quantitative information about the silicate speciation present in the pore wall and at the MBG surface, respectively. The surface modifications were monitored for the three MBGs during their immersion in a simulated body fluid (SBF) for intervals between 30 min and one week. The results were formulated as a reaction sequence describing the interconversions between the distinct silicate species. We generally observed a depletion of Ca2+ ions at the MBG surface, and a minor condensation of the silicate-surface network over one week of SBF soaking. PMID:22349247

  18. Water-limiting conditions alter the structure and biofilm-forming ability of bacterial multispecies communities in the alfalfa rhizosphere.

    Directory of Open Access Journals (Sweden)

    Pablo Bogino

    Full Text Available Biofilms are microbial communities that adhere to biotic or abiotic surfaces and are enclosed in a protective matrix of extracellular compounds. An important advantage of the biofilm lifestyle for soil bacteria (rhizobacteria is protection against water deprivation (desiccation or osmotic effect. The rhizosphere is a crucial microhabitat for ecological, interactive, and agricultural production processes. The composition and functions of bacterial biofilms in soil microniches are poorly understood. We studied multibacterial communities established as biofilm-like structures in the rhizosphere of Medicago sativa (alfalfa exposed to 3 experimental conditions of water limitation. The whole biofilm-forming ability (WBFA for rhizospheric communities exposed to desiccation was higher than that of communities exposed to saline or nonstressful conditions. A culture-dependent ribotyping analysis indicated that communities exposed to desiccation or saline conditions were more diverse than those under the nonstressful condition. 16S rRNA gene sequencing of selected strains showed that the rhizospheric communities consisted primarily of members of the Actinobacteria and α- and γ-Proteobacteria, regardless of the water-limiting condition. Our findings contribute to improved understanding of the effects of environmental stress factors on plant-bacteria interaction processes and have potential application to agricultural management practices.

  19. Erythritol and Lufenuron Detrimentally Alter Age Structure of Wild Drosophila suzukii (Diptera: Drosophilidae) Populations in Blueberry and Blackberry.

    Science.gov (United States)

    Sampson, B J; Marshall, D A; Smith, B J; Stringer, S J; Werle, C T; Magee, D J; Adamczyk, J J

    2017-04-01

    We report on the efficacy of 0.5 M (61,000 ppm) erythritol (E) in Truvia Baking Blend, 10 ppm lufenuron (L), and their combination (LE) to reduce egg and larval densities of wild populations of Drosophila suzukii (Matsumura) infesting fields of rabbiteye blueberries (Vaccinium virgatum) and blackberries (Rubus sp.). Formulations included the active ingredients (lufenuron, erythritol, or both), sugar (in control and erythritol treatments), and Dawn hand-soap applied to plants with pressurized 3-gallon garden spray tanks. The three chemical treatments (E, L, and LE) had no effect on D. suzukii ovipositing in blackberry and blueberry fruit, but they did reduce larval infestation by 75%, particularly densities of first and second instars. Erythritol and lufenuron were equally efficacious compounds as a D. suzukii ovicide and larvicide, but they did not display additive or synergistic activity. Extremely high larval mortality in control fruits show an age structure heavily skewed toward egg output. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by a US Government employee and is in the public domain in the US.

  20. HISTOPATOLOGICAL ALTERATIONS IN LUNGS OF DOGS WITH PULMONARY DIROFILARIASIS IN THE STATE OF RIO DE JANEIRO, BRASIL ALTERAÇÕES HISTOPATOLÓGICAS EM PULMÕES DE CÃES PORTADORES DE DIROFILARIOSE PULMONAR NO ESTADO DO RIO DE JANEIRO, BRASIL

    Directory of Open Access Journals (Sweden)

    Rodrigo Caldas Menezes

    2008-12-01

    Full Text Available The analysis, at light microscopy, of lungs histopathological alterations associated with the infection for Dirofilaria immitis in 33 (thirty three dogs proceeding from Niteroi City, Rio de Janeiro, was carried out. A great diversity in number and intensity of lesions was observed. The most frequent pulmonary parenchyma changes had been interstitial pneumonia, interalveolar septa thickening and infartation, and the less had been focal fibrotic pleurisia and haemorrhage. Yet, in pulmonary artery and branches, the most frequent had been thrombosis and intimal proliferation to the lumen and the less had been pseudoaneurism and sclerosis. It was registered that in the presence of microfilariae in parenchyma, the infiltrates was predominantely formed for mononuclear cells, and in the destruction of the vessel wall, frequently for mixing or mononuclear cells. We concluded that more studies are necessary to the knowledge of the etiology and pathogenesis of Dirofilariasis, after recent studies that consider a bacterium endosymbionts of arthropods, Wolbachia, as the third variable, instead of the classic duality of  host–parasite  relationship.

    KEY WORDS: Dogs, Dirofilaria immitis, histopathological alterations, lungs, pulmonary artery. Foi realizada a análise, à microscopia óptica, das alterações histopatológicas de pulmões associadas à infecção por Dirofilaria immitis em trinta e três cães provenientes do Município de Niterói, Rio de Janeiro. Observou-se uma grande diversidade em número e intensidade de lesões. As alterações mais freqüentes do parênquima pulmonar foram pneumonia intersticial, espessamento do septo alveolar e infarto, enquanto as menos observadas foram pleurisia fibrosa focal e hemorragia. Das alterações mais freqüentes evidenciadas na artéria pulmonar e suas ramificações, citem-se trombose e projeções da íntima para o lúmen, sendo pseudoaneurisma e esclerose pouco evidenciadas. Registraram

  1. Active sites of the cytochrome p450cam (CYP101) F87W and F87A mutants. Evidence for significant structural reorganization without alteration of catalytic regiospecificity.

    Science.gov (United States)

    Tuck, S F; Graham-Lorence, S; Peterson, J A; Ortiz de Montellano, P R

    1993-01-05

    Ferricyanide oxidation of the aryl-iron complexes formed by the reaction of cytochrome P450 enzymes with arylhydrazines causes in situ migration of the aryl group from the iron to the porphyrin nitrogen atoms. The regiochemistry of this migration, defined by the ratio of the four possible N-arylprotoporphyrin IX isomers, provides a method for mapping the topologies of cytochrome P450 active sites. The method has been validated by using it to examine the active site of cytochrome P450cam (CYP101), for which a crystal structure is available. In agreement with the crystal structure, reaction with phenylhydrazine gives a 5:25:70 ratio of the NA:NC:ND (subscript indicates pyrrole ring) N-phenylprotoporphyrin IX isomers. Naphthylhydrazine, however, yields exclusively the NC regioisomer and 4-(phenyl)phenylhydrazine the NA:NC:ND isomers in a 14:40:46 ratio. These isomer ratio differences are readily explained by topological differences between the upper and lower reaches of the active site. Having validated the aryl-iron shift as a topological probe, we used it to investigate the structural changes caused by mutation of Phe-87, a residue that provides the ceiling over pyrrole ring D in the crystal structure of cytochrome P450cam. Mutation of Phe-87 to a tryptophan causes no detectable change in the regiochemistry of camphor hydroxylation and only minor changes in the N-aryl isomer ratios. However, mutation of Phe-87 to an alanine, which was expected to open up the region above pyrrole ring D, severely decreased the proportion of the ND in favor of the NA isomer. Less rather than more space is therefore available over pyrrole ring D in the F87A mutant despite the fact that the regiochemistry of camphor hydroxylation remains unchanged. These results provide evidence for significant structural reorganization in the upper regions of the substrate binding site without alteration of the camphor hydroxylation regiospecificity in the F87A mutant.

  2. Structural brain alterations associated with schizophrenia preceded by conduct disorder: a common and distinct subtype of schizophrenia?

    Science.gov (United States)

    Schiffer, Boris; Leygraf, Norbert; Müller, Bernhard W; Scherbaum, Norbert; Forsting, Michael; Wiltfang, Jens; Gizewski, Elke R; Hodgins, Sheilagh

    2013-09-01

    Conduct disorder (CD) prior to age 15 is a precursor of schizophrenia in a minority of cases and is associated with violent behavior through adulthood, after taking account of substance misuse. The present study used structural magnetic imaging to examine gray matter (GM) volumes among 27 men with schizophrenia preceded by CD (SZ+CD), 23 men with schizophrenia but without CD (SZ-CD), 27 men with CD only (CD), and 25 healthy (H) men. The groups with schizophrenia were similar in terms of age of onset and duration of illness, levels of psychotic symptoms, and medication. The 2 groups with CD were similar as to number of CD symptoms, lifelong aggressive behavior, and number of criminal convictions. Men with SZ+CD, relative to those with SZ-CD, displayed (1) increased GM volumes in the hypothalamus, the left putamen, the right cuneus/precuneus, and the right inferior parietal cortex after controlling for age, alcohol, and drug misuse and (2) decreased GM volumes in the inferior frontal region. Men with SZ+CD (relative to the SZ-CD group) and CD (relative to the H group) displayed increased GM volumes of the hypothalamus and the inferior and superior parietal lobes, which were not associated with substance misuse. Aggressive behavior, both prior to age 15 and lifetime tendency, was positively correlated with the GM volume of the hypothalamus. Thus, among males, SZ+CD represents a distinct subtype of schizophrenia. Although differences in behavior emerge in childhood and remain stable through adulthood, further research is needed to determine whether the differences in GM volumes result from abnormal neural development distinct from that of other males developing schizophrenia.

  3. Two and three dimensional characterization of Zucchini Yellow Mosaic Virus induced structural alterations in Cucurbita pepo L. plants.

    Science.gov (United States)

    Zellnig, Günther; Pöckl, Michael Herbert; Möstl, Stefan; Zechmann, Bernd

    2014-05-01

    Infection of plants by Zucchini Yellow Mosaic Virus (ZYMV) induces severe ultrastructural changes. The aim of this study was to investigate ultrastructural changes during ZYMV-infection in Cucurbita pepo L. plants on the two and three dimensional (2D and 3D) level and to correlate these changes with the spread of ZYMV throughout the plant by transmission electron microscopy (TEM) and image analysis. This study revealed that after inoculation of the cotyledons ZYMV moved into roots [3 days post inoculation (dpi)], then moved upwards into the stem and apical meristem (5 dpi), then into the first true leaf (7 dpi) and could finally be found in all plant parts (9 dpi). ZYMV-infected cells contained viral inclusion bodies in the form of cylindrical inclusions (CIs). These CIs occurred in four different forms throughout the cytosol of roots and leaves: scrolls and pinwheels when cut transversely and long tubular structures and bundles of filaments when cut longitudinally. 3D reconstruction of ZYMV-infected cells containing scrolls revealed that they form long tubes throughout the cytosol. The majority has a preferred orientation and an average length and width of 3 μm and 120 nm, respectively. Image analysis revealed an increased size of cells and vacuoles (107% and 447%, respectively) in younger ZYMV-infected leaves leading to a similar ratio of cytoplasm to vacuole (about 1:1) in older and younger ZYMV-infected leaves which indicates advanced cell growth in younger tissues. The collected data advances the current knowledge about ZYMV-induced ultrastructural changes in Cucurbita pepo. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Independence of protein kinase C-delta activity from activation loop phosphorylation: structural basis and altered functions in cells.

    Science.gov (United States)

    Liu, Yin; Belkina, Natalya V; Graham, Caroline; Shaw, Stephen

    2006-04-28

    Activation loop phosphorylation plays critical regulatory roles for many kinases. Unlike other protein kinase Cs (PKC), PKC-delta does not require phosphorylation of its activation loop (Thr-507) for in vitro activity. We investigated the structural basis for this unusual capacity and its relevance to PKC-delta function in intact cells. Mutational analysis demonstrated that activity without Thr-507 phosphorylation depends on 20 residues N-terminal to the kinase domain and a pair of phenylalanines (Phe-500/Phe-527) unique to PKC-delta in/near the activation loop. Molecular modeling demonstrated that these elements stabilize the activation loop by forming a hydrophobic chain of interactions from the C-lobe to activation loop to N-terminal (helical) extension. In cells PKC-delta mediates both apoptosis and transcription regulation. We found that the T507A mutant of the PKC-delta kinase domain resembled the corresponding wild type in mediating apoptosis in transfected HEK293T cells. But the T507A mutant was completely defective in AP-1 and NF-kappaB reporter assays. A novel assay in which the kinase domain of PKC-delta and its substrate (a fusion protein of PKC substrate peptide with green fluorescent protein) were co-targeted to lipid rafts revealed a major substrate-selective defect of the T507A mutant in phosphorylating the substrate in cells. In vitro analysis showed strong product inhibition on the T507A mutant with particular substrates whose characteristics suggest it contributes to the substrate selective defect of the PKC-delta T507A mutant in cells. Thus, activation loop phosphorylation of PKC-delta may regulate its function in cells in a novel way.

  5. Overexpression of the OsERF71 Transcription Factor Alters Rice Root Structure and Drought Resistance1

    Science.gov (United States)

    Jang, Geupil; Jeong, Jin Seo; Kim, Youn Shic; Ha, Sun-Hwa

    2016-01-01

    Plant responses to drought stress require the regulation of transcriptional networks via drought-responsive transcription factors, which mediate a range of morphological and physiological changes. AP2/ERF transcription factors are known to act as key regulators of drought resistance transcriptional networks; however, little is known about the associated molecular mechanisms that give rise to specific morphological and physiological adaptations. In this study, we functionally characterized the rice (Oryza sativa) drought-responsive AP2/ERF transcription factor OsERF71, which is expressed predominantly in the root meristem, pericycle, and endodermis. Overexpression of OsERF71, either throughout the entire plant or specifically in roots, resulted in a drought resistance phenotype at the vegetative growth stage, indicating that overexpression in roots was sufficient to confer drought resistance. The root-specific overexpression was more effective in conferring drought resistance at the reproductive stage, such that grain yield was increased by 23% to 42% over wild-type plants or whole-body overexpressing transgenic lines under drought conditions. OsERF71 overexpression in roots elevated the expression levels of genes related to cell wall loosening and lignin biosynthetic genes, which correlated with changes in root structure, the formation of enlarged aerenchyma, and high lignification levels. Furthermore, OsERF71 was found to directly bind to the promoter of OsCINNAMOYL-COENZYME A REDUCTASE1, a key gene in lignin biosynthesis. These results indicate that the OsERF71-mediated drought resistance pathway recruits factors involved in cell wall modification to enable root morphological adaptations, thereby providing a mechanism for enhancing drought resistance. PMID:27382137

  6. Conventional tillage decreases the abundance and biomass of earthworms and alters their community structure in a global meta-analysis.

    Science.gov (United States)

    Briones, María Jesús I; Schmidt, Olaf

    2017-10-01

    The adoption of less intensive soil cultivation practices is expected to increase earthworm populations and their contributions to ecosystem functioning. However, conflicting results have been reported on the effects of tillage intensity on earthworm populations, attributed in narrative reviews to site-dependent differences in soil properties, climatic conditions and agronomic operations (e.g. fertilization, residue management and chemical crop protection). We present a quantitative review based on a global meta-analysis, using paired observations from 165 publications performed over 65 years (1950-2016) across 40 countries on five continents, to elucidate this long-standing unresolved issue. Results showed that disturbing the soil less (e.g. no-tillage and conservation agriculture [CA]) significantly increased earthworm abundance (mean increase of 137% and 127%, respectively) and biomass (196% and 101%, respectively) compared to when the soil is inverted by conventional ploughing. Earthworm population responses were more pronounced when the soil had been under reduced tillage (RT) for a long time (>10 years), in warm temperate zones with fine-textured soils, and in soils with higher clay contents (>35%) and low pH (earthworm population responses to RT. Additional meta-analyses confirmed that epigeic and, more importantly, the bigger-sized anecic earthworms were the most sensitive ecological groups to conventional tillage. In particular, the deep burrower Lumbricus terrestris exhibited the strongest positive response to RT, increasing in abundance by 124% more than the overall mean of all 13 species analysed individually. The restoration of these two important ecological groups of earthworms and their burrowing, feeding and casting activities under various forms of RT will ensure the provision of ecosystem functions such as soil structure maintenance and nutrient cycling by "nature's plough." © 2017 John Wiley & Sons Ltd.

  7. Suppression of the phytoene synthase gene (EgcrtB) alters carotenoid content and intracellular structure of Euglena gracilis.

    Science.gov (United States)

    Kato, Shota; Soshino, Mika; Takaichi, Shinichi; Ishikawa, Takahiro; Nagata, Noriko; Asahina, Masashi; Shinomura, Tomoko

    2017-07-17

    susceptibility of cells to light stress. Our results indicate that suppression of EgcrtB causes a significant decrease in carotenoid and chlorophyll content in E. gracilis accompanied by changes in intracellular structures, suggesting that Dtx (de-epoxidized form of diadinoxanthin cycle pigments) contributes to photoprotection of this alga during the long-term acclimation to light-induced stress.

  8. Pulmonary vascular imaging

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    Fedullo, P.F.; Shure, D.

    1987-03-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques.

  9. Pulmonary vascular imaging

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Shure, D.

    1987-01-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques

  10. Intravascular pulmonary metastases

    International Nuclear Information System (INIS)

    Shepard, J.A.O.; Moore, E.H.; Templeton, P.A.; McLoud, T.C.

    1988-01-01

    The diagnosis of intravascular metastatic tumor emboli to the lungs is rarely made. The authors present a characteristic radiographic finding of intravascular lung metastases that they observed in four patients with diagnoses or right atrial myoxoma, invasive renal cell carcinoma, invasive pelvic osteosarcoma, and recurrent pelvic chondrosarcoma. Substantiation of intravascular pulmonary metastases was achieved by means of autopsy, pulmonary artery biopsy, and surgical documentation of tumor invasion of the inferior vena cava or pelvic veins. In all four cases, chest computed tomography (CT) demonstrated branching, beaded opacities extending from the hila into the periphery of the lung in the distribution of pulmonary arteries. In one case, similar findings were observed in magnetic resonance (MR) images of the chest. Follow-up studies in three cases showed progressive enlargement and varicosity of the abnormal pulmonary artery consistent with proliferation of intravascular tumor. In the case of metastatic osteosarcoma, intraluminal ossification was also observed at CT. In three of four cases, pulmonary infarction was demonstrated in the distribution of the abnormal pulmonary arteries seen at CT as small, peripheral, wedge-shaped opacities. The demonstration of progressively dilated and beaded pulmonary arteries in patients with extrathoracic malignancies is suggestive of intravascular lung metastases, particularly when accompanied by peripheral infarction

  11. Shatter cone and microscopic shock-alteration evidence for a post-Paleoproterozoic terrestrial impact structure near Santa Fe, New Mexico, USA

    Science.gov (United States)

    Fackelman, Siobhan P.; Morrow, Jared R.; Koeberl, Christian; McElvain, Thornton H.

    2008-06-01

    Field mapping, morphologic description, and petrographic analysis of recently discovered shatter cones within Paleoproterozoic crystalline rocks exposed over an area > 5 km 2, located ˜ 8 km northeast of Santa Fe, New Mexico, USA, give robust evidence of a previously unrecognized terrestrial impact structure. Herein, we provisionally name this the "Santa Fe impact structure". The shatter cones are composed of nested sub-conical, curviplanar, and flat joint surfaces bearing abundant curved and bifurcating striations that strongly resemble the multiply striated joint surfaces (MSJS) documented from shatter cones at Vredefort dome. The cones occur as a penetrative feature in intrusive igneous and supracrustal metamorphic rocks, are unusually large (up to 2 m long and 0.5 m wide at the base), display upward-pointing apices, and have subvertical, northeastward-plunging axes that crosscut regional host-rock fabrics. Key characteristics of superficially similar, but non-shock-generated conical and striated features are inconsistent with the properties of the Santa Fe cones. In thin section, sub-millimeter-scale, dark, semi-opaque to isotropic veneers on cone surfaces and veinlets within cone interiors closely resemble previously described shock-induced melt features. Microscopic grain alteration, restricted generally to within 1 mm of the cone surfaces, includes random fractures, fluid micro-inclusions, sericite replacement in feldspar, rare kink bands in mica, optical mosaicism, and decorated planar fractures (PFs) and planar deformation features (PDFs) in quartz. The PFs and PDFs are dominated by a basal (0001) crystallographic orientation, which indicate a peak shock pressure of ˜ 5-10 GPa that is consistent with shatter cone formation. Regional structural and exhumation models, together with anomalous breccia units that overlie and crosscut the shatter cone-bearing rocks, may provide additional age constraints for the impact event. The observed shatter cone outcrop

  12. Pulmonary manifestations of leptospirosis

    Directory of Open Access Journals (Sweden)

    Sameer Gulati

    2012-01-01

    Full Text Available Leptospirosis has a spectrum of presentation which ranges from mild disease to a severe form comprising of jaundice and renal failure. Involvement of the lung can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome. Of late, it has been identified that leptospirosis can present atypically with predominant pulmonary manifestations. This can delay diagnosis making and hence optimum treatment. The purpose of this review is to bring together all the reported pulmonary manifestations of leptospirosis and the recent trends in the management.

  13. IDIOPATHIC PULMONARY HEMOSIDEROSIS

    Science.gov (United States)

    Yettra, Maurice; Goldenberg, Erwin; Weiner, Herman

    1960-01-01

    Idiopathic pulmonary hemosiderosis is a rare condition manifested by recurrent pulmonary hemorrhage of unknown cause, diffuse radiologic abnormalities, cough, hemoptysis and moderate to severe hypochromic anemia. Diagnosis can be confirmed by iron stains of the sputum or lung aspiration or by biopsy. Prolonged spontaneous remission may occur without the use of corticosteroid therapy. Studies here reported indicated that the anemia is hypochromic and microcytic anemia of blood loss and iron deficiency, in spite of the presence of large amounts of iron in the pulmonary tissue. Correction of the anemia by intensive iron therapy and transfusion is considered an important part of therapy. ImagesFigure 1.Figure 2.Figure 3. PMID:13787318

  14. Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

    Science.gov (United States)

    González-Guerra, José Luis; Castilla-Cortazar, Inma; Aguirre, Gabriel A; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E; García-Villalón, Ángel Luis

    2017-01-01

    Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

  15. Structural Connectivity Alterations Along the Alzheimer’s Disease Continuum: Reproducibility Across Two Independent Samples and Correlation with Cerebrospinal Fluid Amyloid-β and Tau

    Science.gov (United States)

    Tucholka, Alan; Grau-Rivera, Oriol; Falcon, Carles; Rami, Lorena; Sánchez-Valle, Raquel; Lladó, Albert; Gispert, Juan Domingo; Molinuevo, José Luis

    2018-01-01

    Background: Gray matter changes associated with the progression of Alzheimer’s disease (AD) have been thoroughly studied. However, alterations in white matter tracts have received less attention, particularly during early or preclinical stages of the disease. Objective: To identify the structural connectivity changes across the AD continuum. Methods: We performed probabilistic tractography in a total of 183 subjects on two independent samples that include control (n = 68) and preclinical AD individuals (n = 28), patients diagnosed with mild cognitive impairment (MCI) due to AD (n = 44), and AD patients (n = 43). We compared the connectivity between groups, and with CSF Aβ42 and tau biomarkers. Results: We observed disconnections in preclinical individuals, mainly located in the temporal lobe. This pattern of disconnection spread to the parietal and frontal lobes at the MCI stage and involved almost all the brain in AD. These findings were not driven by gray matter atrophy. Discussion: Using tractography, we were able to identify white matter changes between subsequent disease stages and, notably, also in preclinical AD. Therefore, this method may be useful for detecting early and specific brain structural changes during preclinical AD stage. PMID:29376852

  16. Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype: therapeutic implications for pulmonary hypertension (2015 Grover Conference series).

    Science.gov (United States)

    Pullamsetti, Soni S; Perros, Frédéric; Chelladurai, Prakash; Yuan, Jason; Stenmark, Kurt

    2016-12-01

    Pulmonary hypertension (PH) is a complex and multifactorial disease involving genetic, epigenetic, and environmental factors. Numerous stimuli and pathological conditions facilitate severe vascular remodeling in PH by activation of a complex cascade of signaling pathways involving vascular cell proliferation, differentiation, and inflammation. Multiple signaling cascades modulate the activity of certain sequence-specific DNA-binding transcription factors (TFs) and coregulators that are critical for the transcriptional regulation of gene expression that facilitates PH-associated vascular cell phenotypes, as demonstrated by several studies summarized in this review. Past studies have largely focused on the role of the genetic component in the development of PH, while the presence of epigenetic alterations such as microRNAs, DNA methylation, histone levels, and histone deacetylases in PH is now also receiving increasing attention. Epigenetic regulation of chromatin structure is also recognized to influence gene expression in development or disease states. Therefore, a complete understanding of the mechanisms involved in altered gene expression in diseased cells is vital for the design of novel therapeutic strategies. Recent technological advances in DNA sequencing will provide a comprehensive improvement in our understanding of mechanisms involved in the development of PH. This review summarizes current concepts in TF and epigenetic control of cell phenotype in pulmonary vascular disease and discusses the current issues and possibilities in employing potential epigenetic or TF-based therapies for achieving complete reversal of PH.

  17. Pulmonary Complications Resulting from Genetic Cardiovascular Disease in Two Rat Models

    Science.gov (United States)

    Underlying cardiovascular disease (CVD) has been considered a risk factor for exacerbation of air pollution health effects. Therefore, rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Pulmonary complications and altered iron homeost...

  18. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    Science.gov (United States)

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  19. Centrosome structure and function is altered by chloral hydrate and diazepam during the first reproductive cell cycles in sea urchin eggs

    Science.gov (United States)

    Schatten, H.; Chakrabarti, A.

    1998-01-01

    This paper explores the mode of action of the tranquillizers chloral hydrate and diazepam during fertilization and mitosis of the first reproductive cell cycles in sea urchin eggs. Most striking effects of these drugs are the alteration of centrosomal material and the abnormal microtubule configurations during exposure and after recovery from the drugs. This finding is utilized to study the mechanisms of centrosome compaction and decompaction and the dynamic configurational changes of centrosomal material and its interactions with microtubules. When 0.1% chloral hydrate or 350-750 microM diazepam is applied at specific phases during the first cell cycle of sea urchin eggs, expanded centrosomal material compacts at distinct regions and super-compacts into dense spheres while microtubules disassemble. When eggs are treated before pronuclear fusion, centrosomal material aggregates around each of the two pronuclei while microtubules disappear. Upon recovery, atypical asters oftentimes with multiple foci are formed from centrosomal material surrounding the pronuclei which indicates that the drugs have affected centrosomal material and prevent it from functioning normally. Electron microscopy and immunofluorescence studies with antibodies that routinely stain centrosomes in sea urchin eggs (4D2; and Ah-6) depict centrosomal material that is altered when compared to control cells. This centrosomal material is not able to reform normal microtubule patterns upon recovery but will form multiple asters around the two pronuclei. When cells are treated with 0.1% chloral hydrate or 350-750 microM diazepam during mitosis, the bipolar centrosomal material becomes compacted and aggregates into multiple dense spheres while spindle and polar microtubules disassemble. With increased incubation time, the smaller dense centrosome particles aggregate into bigger and fewer spheres. Upon recovery, unusual irregular microtubule configurations are formed from centrosomes that have lost their

  20. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells

    International Nuclear Information System (INIS)

    Carter, Charleata A.; Hamm, Jonathan T.

    2009-01-01

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-κB (NF-κB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-α and NF-κB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30 μg/ml CSC significantly activated PKC-α, while CSC doses above 20 μg/ml CSC significantly activated NF-κB. As NF-κB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30 μg/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30 μg/ml also induced significant concurrent changes in cell func