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Biomedical subjects

D Buckley

Publications and source records attributed to D Buckley.

At least 55 records · Page 3Linked to original sources
PubMed1996

Lung function in premature rabbits treated with recombinant human surfactant protein-C.

We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.

Animals↗
PubMed1996

Murine IL-10 fails to reduce GVHD despite inhibition of alloreactivity in vitro.

Graft-versus-host disease (GVHD) is a serious complication following allogeneic bone marrow transplantation (BMT). Initial immunologic events that are thought to lead to clinical GVHD include allogeneic antigen presentation, CD4+ T cell proliferation and eventually generation of specific cytotoxic lymphocytes. Interleukin-10 (IL-10) has been shown to inhibit the function of antigen presenting cells (APC) and to reduce lymphocyte proliferation. In this study we investigated the possible role of recombinant murine IL-10 (rmIL-10) as prophylactic treatment of GVHD in a murine BMT model involving B10.BR donor mice (H-2k) and AKR recipients (H-2k). In particular, we wished to determine whether early post-BMT administration of IL-10 would suppress GVHD by interfering with macrophage function and inflammatory cytokine production during the proposed "afferent' phase of GVHD. In MLR assays, rmIL-10 significantly inhibited the proliferation of donor spleen cells when stimulated by irradiated recipient spleen cells in a dose-dependent manner. In murine BMT, rmIL-10 was administered exogenously by intraperitoneal injection of 100 U daily in two different dosage schedules, on days-1, 0, 1, 2, 3, 6 to target the early post-BMT phase, and days-1, 0, 3, 5, 7, 10 after BMT, to administer the same total dose throughout the engraftment period. IL-10 injected mice had lower plasma IL-1 alpha levels on day 3 (12 pg/ml vs 64 pg/ml in controls, P < 0.05), suggesting that both macrophage function and inflammatory cytokine production were inhibited. In contrast to the MLR data, no significant improvement in morbidity and mortality from GVHD was observed. Therefore, IL-10 does not appear to be useful in GVHD prophylaxis.

Animals↗
PubMed1996

The prevalence and direct costs of pre-immunization testing for hepatitis A in general practice.

Two hundred and twenty patients in one general practice travelling to destinations where immunization against hepatitis A virus (HAV) is recommended were tested for their HAV immune status before immunization. Age-specific prevalence of prior immunity to HAV was estimated. The relative costs of pre-immunization testing and immediate immunization were compared. The most cost-effective testing method for this practice was found to be total population testing prior to immunization with HAV vaccine. Individual general practices can estimate the optimal age at which to commence testing for HAV in their own practice population.

Adolescent↗
PubMed1995

The angiotensin sensitivity test and low-dose aspirin are ineffective methods to predict and prevent hypertensive disorders in nulliparous pregnancy.

OBJECTIVE: Our purpose was to assess the efficiency of the angiotensin sensitivity test as a predictive test for preeclampsia and the effectiveness of low-dose aspirin to prevent preeclampsia when commenced at 28 weeks' gestation in angiotensin II-sensitive women. STUDY DESIGN: A total of 495 healthy nulliparous women underwent the angiotensin sensitivity test at 28 weeks' gestation. The angiotensin II-sensitive women were randomized to 60 mg of aspirin or placebo as a subset of a large multicenter, randomized, controlled trial of low-dose aspirin therapy in pregnancy. Assessment of the efficiency of the angiotensin sensitivity test and low-dose aspirin in pregnancy was performed after detailed review of case notes after delivery. The Oxford definition of preeclampsia was used. This includes women without proteinuria but requires blood pressure increments that have been validated to bias the selection to primigravid women. RESULTS: Five women had proteinuric preeclampsia in the angiotensin II-sensitive group randomized to aspirin compared with none in the group randomized to placebo. Overall, 11 (25%) of the women randomized to aspirin had preeclampsia compared with four (11%) randomized to placebo (p < 0.05, not significant). The positive and negative predictive values for the angiotensin sensitivity test were 19% and 87%, respectively. CONCLUSION: The angiotensin sensitivity test is not an effective screening test for preeclampsia, and low-dose aspirin does not prevent preeclampsia when commenced at 28 weeks' gestation in angiotensin II-sensitive women.

Angiotensin II↗
PubMed1995

Interaction of stereo and texture cues in the perception of three-dimensional steps.

A computational method for calibrating stereo using shape-from-texture is described together with five experiments that tested whether the human visual system implements the method. The experiments all tested the prediction that the perceived size of a step between two planar and slanted real surfaces should be affected by texture slant cues projected on to them that are inconsistent with the disparity cues. The predicted effect was observed but the results could be accounted for by a new phenomenon revealed in control conditions: the perceived size of a step between two slanted planes is in part determined by the size of the slants even when texture and stereo cues are held consistent. We conclude that the hypothesis that human stereo is calibrated by texture is not confirmed.

Adolescent↗
PubMed1995

Relation of activity levels to body fat in infants 6 to 12 months of age.

We examined longitudinally the relation between body fatness and physical activity, adjusting for energy intake, in 31 healthy white infants. Measures of physical activity, dietary intake, and body composition were obtained at 6, 9, and 12 months of age. The percentage of body fat was inversely related to activity level, an association that became stronger with increasing age and remained significant after adjustment for dietary energy intake. The percentage of body fat was not related to energy consumed per lean body mass regardless of high or low activity level, nor was energy consumed related to physical activity. We conclude that the percentage of body fat in infants may be related more to their activity levels than to their energy intake.

Adipose Tissue↗
PubMed1995

Integration of stereo, texture, and outline cues during pinhole viewing of real ridge-shaped objects and stereograms of ridges.

Three experiments are reported in which the possible role of blur cues as a factor needing to be taken into account in cue-integration studies involving conflicts between stereo and texture/outline cues was investigated. The earlier suggestion was tested that uncontrolled blur cues might have caused the quite different patterns of cue integration reported for real ridge-shaped objects oriented vertically and for stereograms depicting similar surfaces. Blur cues were manipulated by pinhole viewing intended to render accommodation open loop. The results for real ridges were as predicted by the blur-cue hypothesis: pinhole viewing strengthened texture/outline cues in vertically oriented ridges, thereby diminishing the pattern of stereo dominance hitherto observed for these stimuli (and as observed here in non-pinhole-viewing control conditions and in horizontally oriented ridges). The results for the stereograms did not conform to predictions: pinhole viewing, assumed to remove blur cues from the cue-integration process, still produced the pattern observed in control conditions in which a texture/outline cue for a shallow ridge overwhelmed stereo cues for a steep ridge. This result is against the hypothesis that perhaps blur cues for the stereogram projection surface differentially favoured the shallow texture/outline cues. A new variant of the blur-cue hypothesis is offered to account for this result. The main conclusion from the study is: beware drawing firm conclusions from stereograms about the pattern of cue integration that can be expected when real objects are being viewed. The two situations can produce very different results as far as cue integration is concerned. This is a conclusion with serious implications for the use of stereograms for studying the integration of stereo with other cues.

Adolescent↗
PubMed1995

Mandibular subluxation as an adjunct to exposure of the distal internal carotid artery in endarterectomy surgery. Technical note.

The location of the carotid artery bifurcation and the distance atherosclerotic disease extends distally in the internal carotid artery (ICA) are two factors that contribute to the technical difficulty of carotid endarterectomy. When the bifurcation is high (above C-3) or the disease extends distally, standard approaches may not provide adequate exposure for dissection of plaque or for arteriotomy repair. A simple method of mandibular subluxation is described for added exposure of the distal carotid artery. The criteria for use of this method include: a carotid bifurcation at or above C-2; disease extending to within 2 cm of the skull base; and a small-caliber distal ICA lumen with the expectation of a patch graft extending close to the skull base. In dentulous patients, the mandible is subluxed by attaching an intradental wire from the ipsilateral mandibular bicuspid to an intradental wire around the contralateral maxillary bicuspid. In edentulous patients, a wire is placed around the ipsilateral mandible and secured to a wire placed through the anterior nasal spine. The entire preoperative subluxation requires 10 to 15 minutes under anesthesia and an additional 1 to 2 minutes postoperatively to remove the wires. A single skin suture and an absorbable intraoral suture were placed in some edentulous patients. This technique has been evaluated over a 15-month reference period during which 115 carotid endarterectomies were performed. The criteria stated above were met in seven cases (six patients, 6%) and jaw subluxation was performed preoperatively. An additional 1 to 2 cm of distal exposure was obtained by using this technique and endarterectomy proceeded without complication. A slight "shift" of the standard anatomical landmarks occurred due to the movement of the mandible, which was easily recognized. There were no significant postoperative complaints related to the subluxation; specifically, no temporomandibular joint pain, no other postoperative pain, and no tooth damage were encountered. It is concluded that this relatively simple approach to mandibular subluxation provided significant added exposure to the distal ICA without notably increasing operative time. In addition, there was no morbidity and little additional care was needed when compared with other more radical approaches to high carotid artery exposure.

Aged↗
PubMed1994

Major degradation products of basic fibroblast growth factor: detection of succinimide and iso-aspartate in place of aspartate.

The degradation products of basic fibroblast growth factor (bFGF) were isolated by ion exchange HPLC (HP-IEC) and characterized. The predominant product at pH 5 was a succinimide in place of aspartate15 as determined by LC/MS, N-terminal sequencing, and susceptibility to degradation at pH > 6.5. The rate of appearance of the succinimidyl-bFGF at 22 degrees C was comparable to that reported for small peptides, consistent with a high flexibility predicted for asp15-gly. Tryptic mapping together with [3H]-methylation indicated that iso-aspartate was formed at the position of asp15. Size exclusion HPLC indicated the presence of intact and truncated dimers and trimers which associated through disulfide linkages. Two truncated monomer forms were found that co-eluted by HP-IEC; the cleavages were determined to be at asp28-pro and asp15-gly using LC/MS and N-terminal sequencing. These degradation products which occurred at sites that are away from receptor or heparin binding domains of bFGF remained bioactive in a cell proliferation assay.

Amino Acid Sequence↗
PubMed1994

Lightness perception can be affected by surface curvature from stereopsis.

It is demonstrated that lightness perception can be affected by shape from stereopsis. The starting point was a report by Knill and Kersten that the perceived lightness of a monocularly viewed surface can be affected by outline-contour cues indicating that the surface is three-dimensional (3-D). In that study stimuli consisted of two equally sized abutting regions each having the same vertical linear-intensity ramp, so that the horizontal abutting boundary of the two patches created a sharp change in intensity. When this version of the Craik-O'Brien-Cornsweet stimulus has a rectangular outline, it exhibits the standard simultaneous contrast illusion: equivalent patches in the top and bottom regions appear to have different brightness despite having the same luminance. Knill and Kersten replicated this phenomenon with stimuli whose outline-contour cues were consistent with a flat (planar) surface. They found, however, that the illusion was greatly reduced in stimuli with outlines consistent with two abutting 3-D quarter cylinders, for which equivalent regions in the two halves appeared of similar lightness. Knill and Kersten interpreted this effect in terms of surface-lightness computations that took into account 3-D surface shape to achieve an integrated interpretation of the luminance and shape data. In the present report three experiments are described for which these earlier findings were taken as the starting point. In the first experiment the results were replicated by the use of a different methodology. In the second experiment it was shown that shape-from-stereo can produce similar effects on lightness perception to that caused by shape-from-contour. Real 3-D objects with curved surfaces, luminance profiles of the Knill and Kersten type, and carefully controlled outline-contour cues were used so that the objects appeared flat when viewed monocularly but curved in 3-D when seen binocularly. The third experiment was a control confirming that the stereo effect was not simply due to differences caused by monocular versus binocular viewing. It is concluded that the human visual system uses stereo cues, as well as outline-contour cues, in the interpretation of luminance data to recover surface lightness.

Adult↗
PubMed1993

Interaction of stereo, texture and outline cues in the shape perception of three-dimensional ridges.

We report five psychophysical experiments that employed a cue conflict paradigm to investigate integration by the human visual system of surface shape information from stereo, texture and outline cues. The experiments used convex parabolic and triangular three-dimensional ridge stimuli, with amplitudes (base to peak) in the range 3-9 cm, viewed from 57 cm. The observers' task was to judge ridge amplitude using a scale of two-dimensional drawings of ridge profiles. Cue integration was studied using both vertically and horizontally oriented ridges and both real ridges and stereograms of ridges. The main findings were: (a) stereo strongly dominated all horizontal ridge stereograms; (b) texture and outline cues strongly dominated low (3-6 cm) but not high (9 cm) amplitude vertical ridge stereograms; (c) stereo strongly dominated all real ridge stimuli. These results are evidence against explanations of the vertical/horizontal stereo anisotropy which propose that it derives from stereo mechanisms being tuned only to disparity cues with non-zero second-order spatial derivatives or to disparity discontinuities. They also show that radically different results can be obtained when stereo mechanisms are explored using stereograms and real surfaces and possible reasons for this are discussed.

Adult↗
PubMed1993

Noninvasive assessment of the maternal cerebral circulation by transcranial Doppler ultrasound during angiotensin II infusion.

OBJECTIVE: To examine the relationship between experimentally induced increments in blood pressure and maternal middle cerebral artery flow velocity patterns measured by transcranial Doppler ultrasound (TCD). DESIGN: Prospective experimental study. SETTING: John Radcliffe Maternity Hospital, Oxford. INTERVENTION: Middle cerebral artery flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the temporal cranial approach at 28 weeks gestation before, during and 10 min following an angiotensin II infusion. SUBJECTS: 101 normotensive primiparous women at 28 weeks gestation. RESULTS: A significant rise in blood pressure and fall in heart rate were demonstrated between pre-infusion and maximum angiotensin II infusion (maximum blood pressure) recordings. Simultaneous changes were observed in all flow velocity indices, shown as a decrease in systolic velocity and pulsatility index, and an increase in diastolic and mean velocity (P < 0.0001). These values all returned to baseline levels 10 min post infusion (P < 0.0001). Statistical analysis suggested that the change in flow velocity is related to the rise in blood pressure rather than the direct effect of angiotensin II on the cerebral circulation. CONCLUSION: Transcranial Doppler can detect changes in the cerebral circulation associated with alterations in blood pressure during pregnancy. The technique needs to be evaluated further in hypertensive disease.

Adult↗
PubMed1993

Second trimester ambulatory blood pressure in nulliparous pregnancy: a useful screening test for pre-eclampsia?

OBJECTIVE: To assess the effectiveness of second trimester 24-hour ambulatory blood pressure measurement as a screening test for pre-eclampsia. DESIGN: Prospective interventional study. SETTING: John Radcliffe Maternity Hospital, Oxford, and Queen Charlotte's and Chelsea Hospital, London. SUBJECTS: One hundred and sixty-two normotensive nulliparous women recruited at hospital booking clinics. INTERVENTION: Ambulatory blood pressure was measured at 18 and 28 weeks gestation using the TM2420 monitor. MAIN OUTCOME MEASURE: The development of pre-eclampsia. RESULTS: Awake systolic and mean arterial pressures were significantly increased (P < 0.02) at 18 weeks in those who later developed pre-eclampsia. Those differences were more apparent at 28 weeks at which time the diastolic pressure was also increased (P < 0.01). At both stages of gestation the higher readings were sustained during sleep so that the awake-sleep differences were similar in relation to each outcome. The group with incipient pre-eclampsia had a significantly faster heart rate at both 18 and 28 weeks (P < 0.002) The sensitivity in predicting pre-eclampsia for a mean arterial pressure of 85 mmHg or greater at 28 weeks was 65%, with a positive predictive value of 31%. The sensitivity and positive predictive value for a test combining a mean arterial pressure of 85 mmHg or greater and a heart rate of 90 bpm or greater were 53% and 45%, respectively. CONCLUSION: Although second trimester ambulatory blood pressure is significantly increased in women who later develop pre-eclampsia, the predictive values for blood pressure alone are low. The efficiency of the test is increased by combining the awake ambulatory heart rate and blood pressure measurement together. If an effective method for preventing pre-eclampsia becomes available (commencing at 28 weeks gestation), then awake ambulatory blood pressure and heart rate may have some clinical value as a screening test.

Adolescent↗
PubMed1991

Umbilical artery resistance index as a screening test for fetal well-being. II: Randomized feasibility study.

To determine whether the time taken for fetal assessment could safely be reduced by preliminary screening with Doppler ultrasound, 897 women having fetal assessment in the high-risk unit of the John Radcliffe Hospital, Oxford, were randomly allocated to two groups. In the Doppler group, preliminary assessment was by umbilical artery resistance estimation, and in the fetal heart rate (FHR) group by computerized FHR analysis. To minimize the risk of failing to recognize fetal distress, the criteria for using the nonallocated method as well were deliberately conservative. Thus, 66% of the 1869 Doppler studies done in the Doppler group and 39% of the 2069 FHR tests done in the FHR group needed to be followed by the nonallocated tests. Trained nursing staff performed the Doppler studies as part of their routine duties. Doppler studies were unsuccessful in obtaining a result on 26% of the occasions. Under the above clinical circumstances, preliminary Doppler screening did not reduce the time taken for fetal assessment. There were no significant differences in perinatal outcome between the groups, except that emergency as opposed to elective cesareans were less frequent in the Doppler group. As this finding was not predicted by previous hypothesis, it needs to be confirmed.

Adult↗
PubMed1990

Isotretinoin therapy for acne vulgaris: results in an Irish population.

The results of treatment of cystic and antibiotic-resistant acne vulgaris in 96 consecutive patients with the oral retinoid isotretinoin (13-cis-retinoic acid; Roacentane) are reported retrospectively. The results show that the drug, while toxic in the short term, is highly effective in clearing acne.

Acne Vulgaris↗
PubMed1990

Effects of insulin on diacylglycerol-protein kinase C signaling in rat diaphragm and soleus muscles and relationship to glucose transport.

Insulin was found to provoke rapid increases in diacylglycerol (DAG) content and [3H]glycerol incorporation into DAG and other lipids during incubations of rat hemidiaphragms and soleus muscles. Insulin also rapidly increased phosphatidic acid and total glycerolipid labeling by [3H]glycerol, suggesting that insulin increases DAG production at least partly through stimulation of the de novo pathway. Increased DAG production may activate protein kinase C (PKC) as reported previously in the rat diaphragm. We also observed apparent insulin-induced translocation of PKC from cytosol to membrane in the rat soleus muscle. The importance of insulin-induced increases in DAG-PKC signaling in the stimulation of glucose transport in rat diaphragm and soleus muscles was suggested by 1) PKC activators phorbol esters and phospholipase C stimulation of [3H]-2-deoxyglucose (DOG) uptake and 2) PKC inhibitors staurosporine and polymixin B inhibition of insulin effects on [3H]-2-DOG uptake. Although phorbol ester was much less effective than insulin in the diaphragm, phospholipase C provoked increases in [3H]-2-DOG uptake that equaled or exceeded those of insulin. In the soleus muscle, phorbol ester, like phospholipase C, was only slightly but not significantly less effective than insulin. Similar variability in effectiveness of phorbol ester has also been noted previously in rat adipocytes (weak) and BC3H1 myocytes (strong), whereas DAG, added exogenously or generated by phospholipase C treatment, stimulates glucose transport to a degree that is quantitatively more comparable to that of insulin in each of the four tissues. Differences in effectiveness of phorbol ester and DAG could not be readily explained by postulating that the latter acts independently of PKC, because DAG provoked the apparent translocation of the enzyme from cytosol to membranes in rat adipocytes, and effects of DAG on [3H]-2-DOG uptake were blocked by inhibitors of PKC in both rat adipocytes and BC3H1 myocytes. Collectively, our findings provide further support for the hypothesis that insulin increases DAG production and PKC activity, and these processes are important in the stimulation of glucose transport in rat skeletal muscle and other tissues.

Adipose Tissue↗