• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 519
  • 207
  • 122
  • 62
  • 58
  • 41
  • 23
  • 11
  • 8
  • 4
  • 3
  • 2
  • 2
  • 2
  • 1
  • Tagged with
  • 1279
  • 220
  • 166
  • 140
  • 138
  • 126
  • 120
  • 118
  • 110
  • 103
  • 102
  • 97
  • 83
  • 83
  • 81
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Slow adaptations within the chemoreflexes regulating breathing in humans

Ren, Xiaohui January 1999 (has links)
No description available.
12

Recombinant human erythropoietin therapy for anaemia in patients maintained by continuous ambulatory peritoneal dialysis (CAPD)

Stevens, Judith Mary January 1990 (has links)
No description available.
13

Cerebral metabolism, calcium and zinc during excitotoxic challenge : a multinuclear magnetic resonance spectroscopy study

Thatcher, Nicola M. January 1995 (has links)
No description available.
14

The synthesis and investigation of novel bioreductive anticancer agents

Hsu, Wen-Chuan January 1999 (has links)
No description available.
15

Hypoxia Suppresses DNA Repair: Implications for Cancer Progression and Treatment

Chan, Norman 14 February 2011 (has links)
Acute and chronic hypoxia exists within the microenvironment of solid tumours and drives therapy resistance, genetic instability and metastasis. Despite its importance in solid tumour progression, very little is known regarding the functional consequences of hypoxia-mediated changes in the expression of DNA repair proteins. I studied the relationship between hypoxia and DNA repair using a prolonged chronic hypoxic gas treatment model in a variety of human tumour cell lines to mimic the dynamic state of proliferation and DNA repair in cells distant from the tumour blood vasculature. I observed decreased expression of homologous recombination (HR) and base excision repair (BER) proteins due to a novel mechanism involving decreased protein synthesis. Error-free HR was suppressed 3-fold under 0.2% O2 as measured by the DR-GFP reporter system and functional BER was impaired as assessed with a functional glycosylase assay. This decrease in protein expression and function resulted in increased sensitivity to the DNA damaging agents MMC, cisplatin, H2O2 and MMS. Additionally, chronically hypoxic cells were relatively radiosensitive (OER = 1.37) when compared to acutely hypoxic or anoxic cells (OER = 1.96 - 2.61). As HR defects are synthetically lethal with poly(ADP-ribose) polymerase 1 (PARP1) inhibition, I evaluated the sensitivity of repair-defective hypoxic cells to PARP inhibition. I observed increased clonogenic killing in HR-deficient hypoxic cells following inhibition or depletion of PARP1. PARP-inhibited hypoxic cells accumulated γH2AX foci consistent with an accumulation of collapsed replication forks. Additionally, tumour xenografts exposed to PARP1 inhibition showed increased γH2AX and cleaved caspase-3 expression in hypoxic subregions with suppressed RAD51 protein expression and decreased ex vivo clonogenic survival. I conclude that persistent down-regulation of DNA repair components by the microenvironment could result in faulty DNA repair with significant implications for therapeutic response and genetic instability in human cancers. Specifically, hypoxic cells may be sensitized to PARP inhibitors and other agents targeting repair pathways down-regulated by hypoxia as a consequence of microenvironment-mediated “contextual synthetic lethality”.
16

The effect of hybridization on metabolism and hypoxia tolerance in sunfish

MATHERS, KATHERINE E 30 August 2013 (has links)
Hybridization between species has the potential to exert pleiotropic effects on metabolism. Reduced fitness in hybrids may arise through incompatibilities between nuclear- and mitochondrial-encoded subunits of the enzyme complexes of oxidative phosphorylation. In my thesis, I examined metabolic properties and hypoxia tolerance of bluegill (Lepomis macrochirus), pumpkinseed (L. gibbosus), and their unidirectional F1 hybrids (male bluegill x female pumpkinseed). Electron transport system (ETS) complex activities were examined in isolated mitochondria of bluegill, pumpkinseed and hybrids. The specific activities (units per mg mitochondrial protein) of complexes I, II, and V were indistinguishable between groups; however, both complex III and IV showed indications of depressed activities in hybrid mitochondria. The nature of sequence differences in complex IV catalytic subunits (CO1, CO2, CO3) were minor, however the mtDNA-encoded subunit of complex III (cytochrome b) showed 8 differences between bluegill and pumpkinseed, several of which could have structural consequences to the multimeric enzyme and contribute to the depressed complex III catalytic activity in hybrids. I next examined hypoxia tolerance in bluegill, pumpkinseed and hybrids to see if metabolic disruption in hybrids would lead to a reduced ability to cope with this stress. Though no difference in critical oxygen concentration (Pcrit) was noted, the time to loss of equilibrium (LOE) in 0.8 mg O2 /ml suggests that hybrids and bluegills have a lower hypoxia tolerance than pumpkinseeds. Hybrids showed a unique independence between size and LOE time. Analysis of tissue metabolite levels during normoxia, after LOE, and after a short-term hypoxia exposure suggest that differences in hypoxia tolerance are not due to differences in starting metabolite levels or differential metabolite use during hypoxia exposure. / Thesis (Master, Biology) -- Queen's University, 2013-08-30 15:08:45.779
17

Investigation of cell death and aerenchyma formation in roots of maize (Zea mays l.)

Gunawardena, A. H. L. A. N. January 2000 (has links)
No description available.
18

Hypoxia and the Development of Endothermic Capacity in Chickens (Gallus Gallus)

Neely, Aaron Mackallan 08 1900 (has links)
Adult chickens employ endothermy – internal generation of heat that maintains a constant body temperature (Tb). Prior to hatching, chicken embryos are ectothermic - controlling Tb by external heat sources. Upon hatching, the hatchling transitions from an ectotherm to an endotherm that has been shown to be delayed by hypoxia. In this study, whole animal oxygen consumption () and liver, heart, and skeletal muscle citrate synthase activity (CSA) and were measured during this transition to endothermy in chickens incubated in normoxia and hypoxia (15% O2). The only significant differences in occurred in 48 hour old hatchlings where was lower in normoxic hatchlings. There were no differences in CS activity between age and incubation oxygen levels. Additionally, preliminary 2-D protein gels of embryo and hatchling liver show changes in the proteome upon hatching. Results suggest that hypoxia had no significant effect on CSA and a minimal effect on .
19

Effects of AMPK deletion on the response to hypoxia

Udoh, Utibe-Abasi Sunday January 2016 (has links)
The enzyme adenosine monophosphate activated protein kinase (AMPK), a critical regulator of energy metabolism in the body, is activated by a rise in the cellular AMP: ATP ratio in response to metabolic stresses such as hypoxia. The work in this thesis arises from the recent characterization by Mahmoud, A. (PhD thesis, University of Edinburgh, 2015) of the response to hypoxia of mice lacking the α1 and α2 isoforms of the catalytic subunit of the AMPK molecule. Targeted conditional deletion of the genes encoding the α1 and/or α2 subunits of AMPK in catecholaminergic cells (including cells in the carotid body and the brain) was achieved by crossing mice expressing Cre-recombinase under the control of the tyrosine hydroxylase (TH) promoter, with mice in which either or both α subunits of AMPK were flanked by loxP sequences. AMPKα1/α2-/- mice showed a profoundly abnormal ventilatory response to hypoxia, compared to AMPKα1/α2fl/fl controls. Interestingly however, in vitro recordings from the CSN in isolated carotid body preparations from AMPKα1/α2-/- mice showed that the carotid body afferent response to hypoxia was completely normal in these mice. The abnormal response to hypoxia in AMPKα1/α2-/- mice appears therefore to be due to a deficit in the central, catecholaminergic brainstem neurons involved in respiratory control, where a lack of AMPK activation appears to inhibit the normal hypoxia-induced hyperventilation. While the importance of the peripheral carotid body chemoreceptors in oxygen-sensing has long been established, these findings indicate that the synergistic activation of AMPK in central brainstem neurons by the hypoxic metabolic stress, is also required for the normal response to hypoxia. In this thesis, the responses to hypoxia of AMPKα1/α2-/- mice, AMPKα2-/- mice and AMPKα1/α2fl/fl controls were studied using whole-body plethysmography. The findings showed that AMPKα1/α2-/- mice displayed a respiratory phenotype of longer and increased number of apnoeas coupled with hypoventilation in comparison to both the AMPKα2-/- mice and AMPKα1/α2fl/fl controls confirming the earlier results of Mahmoud (2015). In addition TH immunostaining in the carotid bodies of AMPKα1/α2-/- mice and AMPKα1/α2fl/fl controls was compared to determine if there was any change in the number or density of TH-positive cells in the AMPKα1/α2-/- animals, and the gross result showed a 2-fold decrease in the number of TH- immunopositive cells in the AMPKα1/α2-/- mice as compared to the AMPKα1/α2fl/fl. Intriguingly, if this observation is statistically confirm coupled with the unattenuation of the normal afferent discharge from the carotid bodies of AMPKα1/α2-/- mice then it is plausible that a certain degree of redundancy operates in the physiology of the carotid body with regards to oxygen sensing or the glomus cells type lost may be those not involved in mediating the response to hypoxia. In the main part of this work, c-fos and TH immunohistochemistry were used to investigate the activation of brainstem catecholaminergic neurons by hypoxia, in AMPKα1/α2-/- mice, AMPKα2-/- mice and AMPKα1/α2fl/fl controls. Significant differences in c-fos immunostaining of TH+ve neurons were observed in the SubP region of the NTS, and the C2 region and the A1 region of the ventral respiratory group, implicating these specific regions in the abnormal hypoxic ventilatory response in AMPKα1/α2-/- animals. Catecholaminergic neurons in these brainstem regions are known to play key role in the control of breathing as a loss of these neurons or decrease in their catecholamine content results in severe respiratory abnormalities including respiratory arrhythmias and apnoeas as seen in the Rett syndrome. A significant hyperplasia of the brainstem stem catecholaminergic neurons was also observed in both the AMPKα1/α2-/-and AMPKα2-/- mice consistent with the known inhibitory effects of AMPK activation on cell growth and proliferation. Finally a pilot study was carried out to determine if the respiratory phenotype observed in AMPKα1/α2-/- mice could be replicated using a viral vector to deliver Cre-recombinase to targeted areas in the brainstem in AMPKα1/α2fl/fl mice, to knock out AMPK in specific neuronal subgroups. Although the data obtained from this set of experiments were encouraging, the animals did not show the respiratory phenotype as observed in the conditional knockout mice maybe due to poor targeting of specific brainstem neuronal populations including the SubP region or inadequate transfection of these cells due to low viral titre. One advantage of this pilot work was that responses due to compensatory mechanisms as may be the case in the conditional knock out animals were eliminated. These findings are of interest in understanding the neural control of respiration in hypoxia and acclimatization to altitude, and may also suggest new avenues for therapeutic intervention in breathing disorders such as non-obstructive sleep apnoea. It also raises the possibility that AMPK may be a useful therapeutic tool for disease conditions whose etiology is based on cellular proliferation, such as various forms of cancer and even atherosclerosis.
20

Abnormal vascular structure and function in survivors of prematurity

Barnard, Christopher Richard 01 May 2019 (has links)
One in every 10 infants is born premature, with premature being defined as being born before 37 weeks gestation. The immediate concerns of premature birth are fairly well understood, but the long-term consequences are much less known. Previous studies have shown pulmonary insufficiencies in adulthood, but less have looked at hemodynamic variables. None have investigated exercise and hypoxia intolerance in adults who survived prematurity. The goals of this study were to determine exercise capacity and hemodynamic response during exercise and hypoxia in prematurely born adults, as well as deriving pulse wave velocity in normoxia and hypoxia. Preterm (N=10) and term-born, age-matched subjects (N=12) performed incremental exercise in normoxia (21% O2) or hypoxia (12% O2) until volitional maximum was reached. Subjects had arterial and venous catheters collecting blood gas concentration and blood pressure, and breath-by-breath metabolics gathering ventilation data. Preterm and term-born subjects were well matched for anthropometrics, pulmonary, and exercise capacity values. The preterm adults had elevated heart rates, systolic blood pressure, pulse pressure throughout the exercise protocol in normoxia and hypoxia. The preterm group experienced an increased diastolic blood pressure and mean arterial pressure during normoxic exercise, but had a transient decrease in diastolic blood pressure and mean arterial pressure in hypoxia. Additionally, adults born prematurely had an increase aortic pulse wave velocity (aPWV). With these findings, we aimed to determine if aortic stiffness was increased in premature infants at birth with the neonatal intensive care unit (NICU), or if there was a phenotype of premature aging in this population. Prior to beginning the study with the NICU, the effects of simulation on clinicians and researchers was investigated. Simulation is often used for noninvasive teaching or practicing procedures. No one has looked into the effect simulation has on research being done in an intensive care unit setting. Bay 1 and 2 nurses (n=23) in the NICU were surveyed to rate their thoughts of clinical research, comfort with new research, comfort with simulation, and comfort with researchers not from the NICU. Nurses did not know what aspects of the NICU were overwhelming to researchers nor did they agree that researchers could identify infants stress cue. Nurses also reported discomfort communicating with parents about novel research technology. But overall, nurses support research in the NICU and are comfortable with new research knowing the research team participated in a NICU-specific simulation. A questionnaire was also filled out by researchers (n=3), neonatal intensive care unit physicians (n=3) and nurses (n=3) prior to and after completing a research study simulation. Prior to simulation, scientists showed more unfamiliarity with the infants, the NICU setting, and simulation than did the physicians or nurses. Physicians and nurses, however, were not familiar with the technology the researchers used. The simulation alleviated the differences found among the groups. Simulation improves nurses’ opinions of new technology and researchers coming into the NICU and working with patients. Simulation helps researchers familiarize themselves with the NICU and infants, while also improving the clinicians’ comfort with the technology and methods being used.

Page generated in 0.0473 seconds