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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 73 records · Page 4Linked to original sources
PubMed1998

Recruitment of octamer transcription factors to DNA by glucocorticoid receptor.

Glucocorticoid receptor (GR) and octamer transcription factors 1 and 2 (Oct-1/2) interact synergistically to activate the transcription of mouse mammary tumor virus and many cellular genes. Synergism correlates with cooperative DNA binding of the two factors in vitro. To examine the molecular basis for these cooperative interactions, we have studied the consequences of protein-protein binding between GR and Oct-1/2. We have determined that GR binds in solution to the octamer factor POU domain. Binding is mediated through an interface in the GR DNA binding domain that includes amino acids C500 and L501. In transfected mammalian cells, a transcriptionally inert wild-type but not an L501P GR peptide potentiated transcriptional activation by Oct-2 100-fold above the level that could be attained in the cell by expressing Oct-2 alone. Transcriptional activation correlated closely with a striking increase in the occupancy of octamer motifs adjacent to glucocorticoid response elements (GREs) on transiently transfected DNAs. Intriguingly, GR-Oct-1/2 binding was interrupted by the binding of GR to a GRE. We propose a model for transcriptional cooperativity in which GR-Oct-1/2 binding promotes an increase in the local concentration of octamer factors over glucocorticoid-responsive regulatory regions. These results reveal transcriptional cooperativity through a direct protein interaction between two sequence-specific transcription factors that is mediated in a way that is expected to restrict transcriptional effects to regulatory regions with DNA binding sites for both factors.

Animals↗
PubMed1998

Treatment of traumatic false aneurysm of the thoracic aorta with endoluminal grafts.

PURPOSE: Traumatic false aneurysms of the thoracic aorta presenting at a time remote from the original injury are a rare but complex problem. The treatment of a traumatic false aneurysm by endovascular techniques may offer many advantages over conventional open surgery. METHODS AND RESULTS: Two male patients presented with traumatic false aneurysm of the thoracic aorta after being treated emergently for visceral injuries from a gunshot wound in one and an automobile accident in the other. In both cases, the aneurysm was situated so that only the T11 intercostal artery would be sacrificed by endoluminal exclusion. Commercially available endoluminal stent-grafts (Talent) were deployed successfully. Recovery in both patients was rapid and uneventful with no neurological sequelae. Spiral computed tomographic scans at 1 year indicated sustained aneurysm exclusion and satisfactory endograft position. CONCLUSIONS: A customized endoluminal stent-graft can be used with great accuracy to exclude thoracic false aneurysms, avoiding the potential complexity and morbidity of an open thoracic approach.

Adult↗
PubMed1997

Novel "restoration of function" mutagenesis strategy to identify amino acids of the delta-opioid receptor involved in ligand binding.

A novel "restoration of function" mutagenesis strategy was developed to identify amino acid sequence combinations necessary to restore the ability to bind delta-selective ligands to an inactive delta/mu receptor chimera in which 10 amino acids of the third extracellular loop of the delta receptor were replaced by the corresponding amino acids from the mu receptor (delta/mu291-300). This chimera binds a nonselective opioid ligand but is devoid of affinity for delta-selective ligands. A library of mutants was generated in which some of the 10 amino acids of the mu sequence of delta/mu291-300 were randomly reverted to the corresponding delta amino acid. Using a ligand binding assay, we screened this library to select mutants with high affinity for delta-selective ligands. Sequence analysis of these revertants revealed that a leucine at position 300, a hydrophobic region (amino acids 295-300), and an arginine at position 291 of the human delta-opioid receptor were present in all revertants. Single and double point mutations were then introduced in delta/mu291-300 to evaluate the contribution of the leucine 300 and arginine 291 residues for the binding of delta-selective ligands. An increased affinity for delta-selective ligands was observed when the tryptophan 300 (mu residue) of delta/mu291-300 was reverted to a leucine (delta residue). Further site-directed mutagenesis experiments suggested that the presence of a tryptophan at position 300 may block the access of delta-selective ligands to their docking site.

Amino Acid Sequence↗
PubMed1997

Muscle metabolism changes with training in the nonamputated limb after vascular amputation: interest of phosphorus 31 NMR spectroscopy.

OBJECTIVE: To determine by 31P nuclear magnetic resonance (NMR) spectroscopy the efficacy of training in improving aerobic metabolism of calf muscle in nonamputated limb after recent vascular amputation; to assess the possible associated microcirculatory changes; and to evaluate the need for noninvasive monitoring techniques during training in the nonamputated limb after recent vascular amputation. DESIGN: Prospective study, before and after training. Subjects served as their own controls and were compared with a control group. SETTING: Rehabilitation center of a university hospital. PATIENTS: Ten unilateral vascular amputated patients were included with ankle systolic index between 0.5 and 0.8 in the nonamputated limb, and 10 control subjects without cardiovascular disease or risk factors of atherosclerosis with ankle systolic index of >.95. INTERVENTION: Walking with prosthesis at self-selected velocity over increasing walking distance, arm training at a workload of 60% of a maximal arm test, and analytical exercises of the nonamputated leg (dynamic contractions against low resistance). Subjects received training as inpatients, 5 days a week. MAIN OUTCOME MEASURES: Before and after training, ankle systolic index, forefoot transcutaneous oxygen tension (TcPO2) and veno-arteriolar reflex, and digital plethysmography of the second toe with reactive hyperemia test were studied. Changes in calf muscle pH, phosphocreatine (PCr), and inorganic phosphate (Pi) were measured by 31P NMR spectroscopy at rest and during a plantar flexion-type incremental protocol. RESULTS: There was no significant difference in ankle systolic index (.63 +/- .10 vs .64 + .07) or in TcPO2 (42 +/- 11 vs 44 +/- 10mmHg), and there was reappearance of veno-arteriolar reflex in 3 cases, of a plethysmographic signal in 2 cases, and of the positivity of the reactive hyperemia test in 3 cases. No differences were found with 31P NMR spectroscopy at rest before and after training. At the same workload (1 watt) the difference of the ratio (PCr/(PCr + Pi)) of rest to effort (PCr depletion) was significantly increased in the amputated patients (.423 +/- .159 vs .145 +/- .058; p < .01). This difference of ratio was lower after training (.360 +/- .158 vs .423 +/- .159; p < .05). The pH was less acid between the two periods. CONCLUSION: Vascular monitoring with systolic index and TcPO2 is necessary to follow and to prevent serious ischemia of the nonamputated limb. Claudication is often not detected because of early exhaustion during walking. Training after recent vascular amputation improves the skeletal muscle oxidative capacity.

Amputation, Surgical↗
PubMed1997

Rupture of an abdominal aortic aneurysm causes priming of phagocytic oxidative burst.

PURPOSE: The purpose of this investigation was to determine whether rupture and repair of an abdominal aortic aneurysm induced activation of phagocyte oxidant burst, reflecting a systemic inflammatory state, when compared with elective abdominal aortic aneurysm (AAA) repair. METHODS: Blood samples were harvested from 22 patients with elective AAA and 15 patients with ruptured AAA. Phagocyte oxidant activity was measured in response to a panel of activators with luminol and lucigenin as chemiluminescent substrates. Activity of the complement pathways was measured with plasma levels of C3a des arg. RESULTS: Elective AAA repair resulted in significant elevation in phagocyte count and oxidative activity after surgery in response to maximal dose phorbol myristate acetate (PMA) when compared with the baseline sample. In patients with ruptured AAA the oxidative activity of phagocytes was significantly increased in response to both unopsonized zymosan (899.8 +/- 192 ruptured vs 300 +/- 40 elective, p < 0.01) and maximal dose PMA (8769 +/- 2011 vs 3508 +/- 382, p < 0.01) compared with elective cases at the initial sampling. Phagocyte priming has occurred by way of two distinct pathways: receptor-mediated (unopsonized zymosan, CR3 receptor) and receptor-independent (PMA, protein kinase c). CONCLUSIONS: Rupture of an AAA resulted in priming of the phagocyte oxidant capacity before operative repair compared with elective AAA. Phagocyte activation is a critical component of the systemic inflammatory response that may contribute to the high incidence of systemic organ dysfunction and death in this patient group.

Acridines↗
PubMed1997

Severe opioid toxicity and somatization of psychosocial distress in a cancer patient with a background of chemical dependence.

A case of severe opioid toxicity is described in a 52-year-old cancer patient. The patient presented with classical clinical features of central hyperexcitability associated with opioid toxicity: delirium, myoclonus, hallucinations, hyperalgesia, and a possible seizure. This patient had a background of severe psychosocial distress and somatization in addition to a history of benzodiazepine dependence and alcohol abuse. The occurrence of opioid toxicity in this patient highlights the risks of a unidimensional approach to cancer pain, which ignores the non-organic components of pain, such as psychosocial distress, which will not respond to escalating doses of opioid medication.

Alcoholism↗
PubMed1997

Bifurcated stent-graft for abdominal aortic aneurysm.

The purpose of this study was to examine bifurcated stent-graft implantation for abdominal aortic aneurysm. Fifty-seven patients were treated and followed with serial computed tomography scans for up to 3 years. Patients were allocated to three groups (first 20, second 20, last 17) according to when the repair was performed. Successful treatment is defined as exclusion of the aneurysm from the circulation, based on contrast computed tomography. Success rates in the three groups were 55%, 70% and 100%. Perigraft leak (endoleak) was present on initial assessment in 4/20, 2/20 and 1/17. Two of these aneurysms ruptured early in the postoperative period. Thereafter, leaks were sought and treated aggressively. Kinking and thrombosis occurred in six of the first 20 patients, but did not occur in any of the last 37 patients, in whom the graft limbs were routinely stent-supported throughout. Infrarenal implantation in very a short neck (< 10 mm), or a thrombus-lined neck was associated with proximal stent migration. In conclusion, changes in patient selection and technique have led to a steady rise in the short-term success rate of the stent-grafted implantation.

Aneurysm, Ruptured↗
PubMed1997

Actinomycosis oto-mastoiditis.

Actinomycosis of the temporal bone is uncommon. There have only been 24 cases previously reported in the English literature. The responsible organism is Actinomyces israelii, an anaerobic filamentous Gram positive bacterium. While the cervico-facial region is the most common site of the disease, involvement of the temporal bone is rare. The diagnosis can sometimes be made clinically by identification of sulphur granules in a glue-like substrate but in all cases involving the temporal bone, the diagnosis has been made at histopathology. Effective therapy consists of surgery followed by the long-term administration of penicillin.

Actinomycosis↗
PubMed1997

Ventilation tube duration versus site of placement.

BACKGROUND: The duration a ventilation tube remains in the tympanic membrane is thought to be related to the design of the ventilating tube, and to the site of placement of the ventilation tube into the tympanic membrane. Theoretically a ventilating tube placed superiorly should remain longer than one placed inferiorly. METHODS: A prospective study was designed to test the hypothesis that ventilation tubes placed into the antero-superior quadrant of the tympanic membrane remained longer than those placed into the antero-inferior quadrant. RESULTS: In 106 children no statistically significant difference in duration was identified using three designs of ventilation tube. CONCLUSIONS: Ventilating tubes placed antero-superiorly into the tympanic membrane do not have a longer duration than those placed antero-inferiorly.

Child↗
PubMed1997

Computer-aided cognitive rehabilitation: possible application to the attentional deficit of schizophrenia, a report of negative results.

The cognitive deficits associated with schizophrenia commonly include impairment in attention, which may contribute to difficulties with learning, memory, and executive function. This study evaluated the effectiveness of computer-aided training of attentional skills in schizophrenia. Two groups of schizophrenic subjects (9 men and 1 woman) were matched for age, estimated premorbid IQ, and positive and negative symptom scores. Both groups were assessed using a battery of attentional tests. Subjects then received either six 1-hr. computer-aided cognitive rehabilitation sessions (experimental condition) or six sessions of graphics-based computer games (control condition). Both groups were reassessed with attentional measures. There was significant improvement on only one test, a letter-cancellation task. This improvement was evident in both groups suggesting that this was a practise effect. Apart from the letter-cancellation test, subjects undertaking the computer-aided rehabilitation treatment did not show significant improvement on any attentional tasks.

Adult↗
PubMed1997

The representation of nonstructural information in visual memory: evidence from image combination.

Two experiments investigated the differential representation of the figure and ground of a picture in visual short-term and long-term memory. It is known (Hitch, Brandimonte, & Walker, 1995) that subjects find it more difficult to combine mental images of two separately presented pictures in order to identify a novel form when the two pictures are incongruent in color (i.e., when a black-on-white line drawing has to be combined with a white-on-black drawing). In the present experiments, the figures were depicted in solid form to allow color congruity to be varied independently for figure and ground. Results showed a clear impairment in image combination when the to-be-combined figures were incongruent in color (black-on-gray and white-on-gray) but not when their grounds were incongruently colored (gray-on-black and gray-on-white). In this way, image combination was seen to be supported by a representation of the object depicted in the picture rather than by a literal representation of the picture itself (i.e., a pictorial code). In line with previous findings, the same representation was seen to support image combination based on short-term memory (Experiment 1) and long-term memory (Experiment 2), provided that in the latter case verbal recoding was precluded. When verbal recoding was allowed, image combination based on long-term memory was insensitive to color congruity, implying the involvement of a more abstract structural representation.

Adolescent↗
PubMed1997

[Study of myocardial viability after myocardial infarction. Value and limits of magnetic resonance imaging compared with myocardial scintigraphy].

The aim of this study was to compare myocardial thickness measured by magnetic resonance imaging and quantified fixation of thallium. Twenty-one patients 61.2 +/- 11 years were investigated after myocardial infarction of the anterior wall in 8 cases, inferior in 10 cases, lateral in 2 cases and apical in one case. The mean angiographic ejection fraction was 46.5 +/- 19%. Myocardial scintigraphy was performed after an exercise or pharmacological stress test and followed by a study of redistribution. The data was analysed by a quantitative method. Magnetic resonance imaging was performed with vertical and horizontal long axis views in systole and diastole with division of the left ventricle into the same 12 regions. Three groups were defined according to fixation during redistribution. Group I: regions with fixation > 80% (n = 155); group II: 60 to 80% (n = 78); group III: fixation < 60% (n = 19). All measurement of myocardial thickness were correlated (p < 0.01) with the fixation of thallium during redistribution. Systolic thickening, was significantly greater in group I (3.80 +/- 3.1 mm) than in groups II (2.20 +/- 3.8 mm) and III (1.56 +/- 2.4 mm) in which it was comparable. Regions in group III had systolic (8.61 +/- 3.53) and diastolic (6.89 +/- 3.3 mm) thicknesses significantly inferior to those in groups I (13.79 +/- 4.4 mm: 9.95 +/- 2.8 mm) and II (11.59 +/- 5.5 mm: 9.38 +/- 2.9 mm). Ninety per cent of regions with a systolic thickness of over 10 mm had fixation during redistribution of more than 60%. This study shows that myocardial thickness is correlated to scintigraphic data. The systolic thickness over 10 mm would confirm the viability of a given region.

Adult↗
PubMed1996

Effects of hormone replacement therapy on the circadian pattern of atherothrombotic risk factors.

Onset of acute atherothrombotic events (acute myocardial infarction, unstable angina, ischemic stroke) exhibit a circadian pattern that parallels the diurnal pattern of endogenous fibrinolytic activity. Hormone replacement therapy in postmenopausal women has been shown to enhance fibrinolytic capacity by lowering plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator inhibitor (tPA) antigen values. We evaluated the impact of 4 weeks of estrogen alone (Premarin 0.625 mg/day) and 2 weeks of estrogen plus progesterone (Provera 2.5 mg/day) on PAI-1 and tPA in 17 postmenopausal women at multiple time points to assess hormone impact on the diurnal pattern of fibrinolytic potential. At baseline, both PAI-1 and tPA exhibited circadian variability. Estrogen alone selectively lowered 8 A.M. PAI-1 (35.8 +/- 7.1 ng/ml at baseline, 19.8 +/- 3.7 ng/ml on estrogen; p = 0.0002 vs baseline). There was no significant change in the noon or 4 P.M. values, and the diurnal pattern was attenuated. The 8 A.M. PAI-1 remained low at 17.1 +/- 3.6 ng/ml (p = 0.0001 vs baseline) with total loss of the circadian rhythm. Estrogen supplementation reduced tPA antigen at all time points, and the diurnal pattern, although blunted, persisted. Addition of progesterone to estrogen did not reverse effects of the estrogen alone phase of either PAI-1 or tPA values. This hormone-associated reduction of PAI-1 was observed despite increased triglycerides, a known inducer of PAI-1 levels. These observations suggest that hormone replacement therapy may protect postmenopausal women from excess early morning acute ischemic events.

Circadian Rhythm↗