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Biomedical subjects

M Doyle

Publications and source records attributed to M Doyle.

At least 73 records · Page 4Linked to original sources

Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor.

A surface plasmon resonance (SPR) biosensor was used to study the interaction of human interleukin-5 (hIL5) with its receptor. IL5 is a major growth factor in the production and activation of eosinophils. The receptor for IL5 is composed of two subunits, alpha and beta. The alpha subunit provides the specificity for IL5 and consists of an extracellular soluble domain, a single transmembrane region and a cytoplasmic tail. We expressed the soluble domain of the human IL5 receptor alpha subunit (shIL5R alpha) and human IL5 (hIL5) in Drosophila. Both hIL5 and shIL5R alpha were immobilized separately through amine groups onto the carboxylated dextran layer of sensor chips of the BIAcore (Pharmacia) SPR biosensor after N-hydroxysuccinimide/carbodiimide activation of the chip surface. Interactions were measured for the complementary macromolecule, either shIL5R alpha or hIL5, in solution. Kinetics of binding of soluble analyte to immobilized ligand were measured and from this the association rate constant, dissociation rate constant and equilibrium dissociation constant (Kd) were derived. With immobilized shIL5R alpha and soluble hIL5, the measured Kd was 2 nM. A similar value was obtained by titration calorimetry. The Kd for Drosophila expressed receptor and IL5 is higher than the values reported for proteins expressed in different systems, likely due to differences in the methods of interaction analysis used or differences in protein glycosylation. Receptor-IL5 binding was relatively pH independent between pH 6.5 and 9.5. Outside this range, the dissociation rate increased with comparatively little increase in association rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adaptive Fourier threshold filtering: a method to reduce noise and incoherent artifacts in high resolution cardiac images.

We introduce an image processing method which reduces white noise and random artifacts in sets of high resolution, time resolved images. At each pixel, the processing consists of: 1) the isolation of a time intensity curve (TIC), 2) Fourier transformation of each TIC, 3) application of a threshold to remove low intensity coefficients, 4) inverse transformation to generate noise reduced TICs which are recombined to form images with improved signal-to-noise ratio (SNR). Noise filtering by Fourier thresholding is demonstrated on a set of cardiac images, resulting in a reduction of the noise energy by approximately 90%.

Artifacts↗

A non-invasive optical technique for intrapartum fetal monitoring: preliminary clinical studies.

A relatively new optical method based on near infra-red spectroscopy was evaluated in preliminary clinical trials for noninvasive intrapartum fetal monitoring. The measurements were performed using mainly the light reflection mode of monitoring. Continuous monitoring of changes in the concentrations of oxygenated and deoxygenated haemoglobin and thus changes in total haemoglobin concentration in the fetal brain was achieved. It was found that uterine contractions can influence in a distinctive manner the near infra-red derived cerebral haemoglobin concentration changes in the fetus. The results indicate that near infra-red spectroscopy could offer a non-invasive real-time monitoring method for in vivo monitoring of blood oxygenation in the fetal brain. We conclude that this technique may be useful for intrapartum fetal monitoring and in predicting fetal cerebral hypoxia.

Brain Chemistry↗

Persistent binocular diplopia following cataract surgery: aetiology and management.

We studied all patients referred to the orthoptic department with binocular diplopia following cataract surgery between January 1991 and June 1993. Persistence of diplopia for a minimum of 3 months after cataract surgery was required for inclusion in the study. Eighty-one patients (2% of all patients who underwent cataract surgery during this time) satisfied the entry criteria. The patients fell into two groups: non-traumatic and traumatic cataracts. Horizontal deviations were seen in 24 patients. Vertical deviations were seen in 8 patients and a combined horizontal and vertical deviation was seen in 49 patients. Fresnel prisms were used to manage the diplopia in 58 patients. Of these, 48 patients in the non-traumatic group regained binocular single vision with this prism while 10 in the traumatic group benefited. Mechanical and sensory causes are discussed.

Adolescent↗

Hypocotyl expression and light downregulation of the soybean tubulin gene, tubB1.

The tubB1 beta-tubulin gene of Glycine max (previously named s beta 1) is highly expressed only in rapidly elongating regions of etiolated seedling hypocotyls and this expression is strongly downregulated when the seedlings are exposed to light. Primer extension demonstrated that the gene was transcribed in these tissues and contained two sites of transcriptional initiation. To determine the mechanism regulating tubB1 expression, a chimeric reporter gene was constructed by fusing 5' upstream regions of tubB1 to a promoterless beta-glucuronidase (GUS) gene and these constructs were introduced into protoplasts by electroporation. Strong transient expression of the reporter gene was obtained after electroporation of chimeric constructs containing 1 kb of tubB1 5' upstream sequence into tobacco protoplasts. Deletion of the distal most 300 bp from the 5' sequence of tubB1 enhanced expression, suggesting the possibility of a negative transcriptional regulator in this region. Additional deletions of the 5' sequence reduced expression substantially. Constructs containing a tubB1 3' terminus were expressed at much lower levels than those containing a nopaline synthase (NOS) 3' terminus. The tubB1-GUS chimeric gene also was introduced into tobacco by Agrobacterium-mediated Ti plasmid transformation and the organ-specific expression pattern of the chimeric gene was determined in seedlings of the transgenic plants. Hypocotyls exhibited strong GUS activity when the seedlings were germinated in darkness, but lacked the GUS enzyme when the seedlings were germinated in the light.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Coronary artery imaging in multiple 1-sec breath holds.

The act of breathing results in considerable bulk cardiac motion, thus breath holding is usually required to image the coronary arteries. Normally, breath hold periods of about 15 sec are required, which can be difficult to sustain over several minutes. We introduce a breath holding strategy that only requires a 1-sec breath hold in every 4 sec. A set of cross-sectional images is acquired in approximately 10 min, and 3-dimensional renderings of the coronary tree are produced from these.

Artifacts↗

Study of human immunodeficiency virus resistance to 2'-3'-dideoxyinosine and zidovudine in sequential isolates from pediatric patients on long-term therapy.

Resistance to zidovudine (3'-azido-3'-deoxythymidine) and 2',3'-dideoxyinosine (ddI) has been reported for human immunodeficiency virus (HIV) isolates from adults, but little is known about these drugs in children. A new micrococulture assay was developed for evaluation of drug susceptibility using single-passage HIV isolates cocultured with peripheral blood mononuclear cells from healthy donors. HIV isolates from children treated with zidovudine or ddI were evaluated to define the emergence of resistance to these antiretroviral agents. Four patients were treated with ddI and 3 with zidovudine for > 15 months. There was a > or = 20-fold decrease in susceptibility to ddI for sequential isolates of HIV recovered from 4 patients treated with ddI for 22-31 months and a 4- to 10-fold decrease in susceptibility to zidovudine in 3 patients. HIV isolates from 3 patients treated with ddI or zidovudine alone showed a minor amount of cross-resistance to the other antiretroviral agent. Results indicate the importance of monitoring antiretroviral drug susceptibility of HIV isolates when assessing clinical deterioration in children treated for > 1 year.

Child↗

Role of radiation therapy in management of pulmonary Kaposi's sarcoma.

Although the incidence of AIDS-related Kaposi's sarcoma (KS) has been declining in recent years, the uncommon and unfortunate progression to symptomatic pulmonary KS still represents a significant therapeutic challenge. Pulmonary KS generally occurs in the late stages of the disease. Review of the literature and of the experience of the Walter Reed Army Medical Center Radiation Oncology Service suggests that early intervention with radiation therapy may provide palliation of the often distressing symptoms that herald KS-induced respiratory failure and may have a favorable impact on quality of life and survival time.

AIDS-Related Opportunistic Infections↗

A randomised prospective study comparing the new vacuum extractor policy with forceps delivery.

OBJECTIVE: To compare assisted vaginal delivery by forceps with delivery by vacuum extractor, where a new vacuum extractor policy was employed which dictated the cup to be used in specific situations. DESIGN: Multicentre randomised controlled trial. SETTING: Four district general hospitals in the West Midlands. SUBJECTS: Six hundred-seven women requiring assisted vaginal delivery, of whom 296 were allocated to vacuum extractor delivery and 311 to forceps. MAIN OUTCOME MEASURES: Delivery success rate, maternal perineal and vaginal injuries, maternal anaesthetic requirements, neonatal scalp and facial injuries. RESULTS: Of the vacuum extractor group, 85% were delivered by the allocated instrument compared to 90% in the forceps group (odds ratio (OR) 0.64; 95% confidence intervals (CI) 0.4-1.04). However, more women in the vacuum extractor group were delivered vaginally (98%) than in the forceps group (96%). There were significantly fewer women with anal sphincter damage or upper vaginal extensions in the vacuum extractor group (11% vs 17%, OR 0.6; 95% CI, 0.38-0.97). There were significantly fewer women in the vacuum extractor group requiring epidural or spinal anaesthetics (25.4% vs 32.7%, OR 0.69; 95% CI 0.49-0.99) or general anaesthetics (1% vs 4%, OR 0.17; 95% CI 0.04-0.76). Although there were significantly more babies in the vacuum extractor group with cephalhaematomata (9% vs 3%, OR 3.3; 95% CI 1.4-7.4) there were fewer babies in the vacuum extractor group with other facial injuries. There were three babies in the forceps group with unexplained neonatal convulsions. CONCLUSIONS: Assisted vaginal delivery using the new vacuum extractor policy is associated with significantly less maternal trauma than with forceps. Further studies are required to assess neonatal morbidity adequately.

Adult↗

Slice thickness reduction by partial overlapping presaturation.

We present a new approach to slice thickness reduction that does not require strengthening the selection gradient or increasing the RF pulse duration. The basis of the approach is to employ a thick slice and suppress a portion of its width, thereby forming a thin slice. Two distinct implementations of the technique are introduced and demonstrated by imaging slice profiles in a phantom and generating images of a volunteer's knee.

Humans↗

The relationship between relative's Expressed Emotion and schizophrenic relapse: an Australian replication.

We report a predictive study, carried out in Sydney Australia, investigating the association between the Expressed Emotion (EE) status of the household to which the patient is discharged and schizophrenic relapse. Expressed Emotion was not related to illness severity either at admission or discharge, but was related to variables reflecting chronicity and employment history. There was a significant association between returning to a high EE household and both re-hospitalisation and relapse. The significant association between EE and relapse held only for: patients not on medication, males, and those patients in high contact with their relatives. A discriminant function analysis found that decline in occupational status and the number of critical comments expressed by the relative were the strongest predictors of relapse. The results presented here are consistent with the majority of published reports on EE and relapse and contradict the negative findings of a recently published but smaller study also carried out in Sydney.

Adult↗

The Sydney intervention trial: a controlled trial of relatives' counselling to reduce schizophrenic relapse.

The result of a psychosocial intervention which aimed to reduce schizophrenic relapse through relatives' counselling is presented. Thirty-six schizophrenic patients living in high Expressed Emotion (EE) parental households were randomly allocated to an intervention or control group. The parents of patients allocated to the intervention were offered ten weekly sessions of counselling. The patient was not included in these sessions. Patients in both groups received standard after-care of medication and support. Relapses in the intervention group, although fewer, were not significantly different from the control group. Given the impressive evidence in favour of family interventions in reducing relapse rates in schizophrenic patients possible reasons for this result are discussed. Aspects of the intervention described here, exclusion of the patient, no control over the patients' medication or involvement with their management, short duration of intervention and lack of individual assessment, could explain this finding. This negative result is important in indicating what factors should be included in an effective psychosocial intervention.

Adult↗

Non-invasive optical monitoring of cerebral blood oxygenation in the foetus and newborn: preliminary investigation.

Near infra-red spectroscopy was applied as a non-invasive and continuous technique for the in vivo monitoring of blood and tissue oxygenation in human neonates. Monitoring of cerebral blood oxygenation in the wavelength range 775-904 nm was carried out on preterm infants after inducing a transient mild hypoxic change; the measurements were performed either by the transmission or reflection (backscattering) mode of monitoring. The results of these investigations were used to assess the application of the technique to foetal monitoring. A series of foetal monitoring studies was performed to investigate the influence of maternal contractions on foetal cerebral blood oxygenation. Although only changes in haemoglobin concentration can be monitored at present, the results suggest that near infra-red monitoring could provide a non-invasive, real-time monitoring method in intensive neonatal and intrapartum care.

Brain↗

Outflow refreshment angiography: a bright blood, bright static tissue technique.

A new "bright blood" strategy, outflow refreshment imaging, is introduced in which a number of overlapping slices are excited in rapid succession. Flowing spins that refresh each overlapped slice portion contribute a bright signal. Additionally, static tissue in each non-overlapped slice portion also yields a bright signal. However, the flow/static contrast is comparable to that produced in inflow refreshment images, and angiograms can be generated by conventional maximum intensity projection processing. The dual ability to visualize angiograms and static tissue images is a major benefit of the strategy. Computer simulations of flow sensitivities and in vivo results are presented which compare the outflow and inflow refreshment imaging strategies.

Blood Flow Velocity↗