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Biomedical subjects

B Murray

Publications and source records attributed to B Murray.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expression, purification and immunological characterization of the transforming protein E7, from cervical cancer-associated human papillomavirus type 16.

E7 is the major oncogenic protein produced in cervical cancer-associated human papillomavirus type 16 (HPV16). This protein was expressed in Escherichia coli as a glutathione-S-transferase (GST) fusion protein. E7-enriched inclusion bodies were collected from bacterial lysates, were solubilized in 10 M urea, and the protein was purified using anion exchange column chromatography. After removal of endotoxin with serial Triton X-114 extractions, material of high purity (about 90%) was obtained, which is suitable for use in a human clinical trial. This material was immunogenic, and when used as a vaccine, protected mice against challenge with an HPV16 E7 DNA transfected tumour cell line. Based on this observation, the E7GST fusion protein is currently being used in a human clinical trial of a vaccine against HPV16-induced cervical cancer. This fusion protein could be cleaved with thrombin to remove the GST fusion part and further purified by preparative SDS gel electrophoresis to obtain free E7 with > 98% purity.

Animals↗
PubMed1999

Implantation metastasis of primary central nervous system lymphoma complicating radiotherapy outcome.

Computed tomography-guided stereotactic biopsy is commonly used in the diagnosis of brain lesions. An uncommonly reported risk of the procedure is the potential of implantation metastasis. This phenomenon has been reported in central nervous system malignancies. Although the role of prophylactic local radiotherapy at biopsy sites is well recognized in solid tumors, it has not been reported to occur after stereotactic biopsy of a brain tumor. The authors report a case of locally progressive primary central nervous system lymphoma at an unsuspiciously underdosed biopsy site complicating radiotherapy outcome.

Adult↗
PubMed1999

The development of target-eye-view maps for selection of coplanar or noncoplanar beams in conformal radiotherapy treatment planning.

Three-dimensional conformal radiotherapy allows the use of tightly conformed, multiple coplanar or noncoplanar beams. However, visualizing the spatial relationships between the target volume and adjacent critical structures is not always obvious or intuitive. Tools such as beam's eye view (BEV) have aided in this process and been very useful. In this study, a target-eye-view (TEV) map is developed as a functional extension of BEVs. The TEV map for a critical structure is created by checking the BEVs for all gantries and table rotations. For each possible BEV, the amount of overlap between the planning target volume (PTV) and the organ at risk (OAR) is determined. This information is presented in a Mercator spherical map, where the color tone indicates the amount of overlap between the PTV and the OAR. A composite TEV map is then created by summing the TEV grading scores for all OARs. The composite map shows beam orientations with the most overlap being light and the least overlap being dark, thus simplifying the selection of appropriate beam angles. The accuracy of the TEV maps has been confirmed separately with corresponding BEVs generated by a three-dimensional treatment planning system.

Algorithms↗
PubMed1999

Effectiveness of nurse executives: measurement of role factors and attitudes.

This article describes the outcome of a survey of 40 nurse executives and 56 influential colleagues. Both groups agreed that leadership was the most important quality for the executive role. The nurses' primary focus was resolution of patient care problems. Influential colleagues stated resource allocation and initiation of change were two qualities needing improvement. The nurses rated themselves high in confidence about their job responsibilities, scored relationships as the most satisfying attribute, and cited provision of quality health care as the greatest advantage of their position. The greatest disadvantage was lack of administrative support. The results suggest the educational preparation needed for nurse executives.

Attitude of Health Personnel↗
PubMed1998

JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension.

MAP kinase (MAPK) cascades are composed of a MAPK, MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK). Despite the existence of numerous components and ample opportunities for crosstalk, most MAPKs are specifically and distinctly activated. We investigated the basis for specific activation of the JNK subgroup of MAPKs. The specificity of JNK activation is determined by the MAPKK JNKK1, which interacts with the MAPKKK MEKK1 and JNK through its amino-terminal extension. Inactive JNKK1 mutants can disrupt JNK activation by MEKK1 or tumor necrosis factor (TNF) in intact cells only if they contain an intact amino-terminal extension. Mutations in this region interfere with the ability of JNKK1 to respond to TNF but do not affect its activation by physical stressors. As JNK and MEKK1 compete for binding to JNKK1 and activation of JNKK1 prevents its binding to MEKK1, activation of this module is likely to occur through sequential MEKK1:JNKK1 and JNKK1:JNK interactions. These results underscore a role for the amino-terminal extension of MAPKKs in determination of response specificity.

Animals↗
PubMed1998

Inhibition of the p44/42 MAP kinase pathway protects hippocampal neurons in a cell-culture model of seizure activity.

Excessive release of glutamate and the subsequent influx of calcium are associated with a number of neurological insults that result in neuronal death. The calcium-activated intracellular signaling pathways responsible for this excitotoxic injury are largely unknown. Here, we report that PD098059, a selective inhibitor of the calcium-activated p44/42 mitogen-activated protein kinase (MAP kinase) pathway, reduces neuronal death in a cell-culture model of seizure activity. Dissociated hippocampal neurons grown chronically in the presence of kynurenate, a broad spectrum glutamate-receptor antagonist, and elevated amounts of magnesium exhibit intense seizure-like activity after the removal of these blockers of excitatory synaptic transmission. A 30-min removal of the blockers produced extensive neuronal death within 24 h as assayed by the uptake of trypan blue and the release of lactate dehydrogenase. Phospho-p44/42 MAP kinase immunoreactivity after 30 min of seizure-like activity was present in many neuronal somata and dendrites as well as some synaptic terminals, consistent with both the presynaptic and postsynaptic effects of this pathway. The addition of PD098059 (40 microM; EC50 = 10 microM) during a 30-min washout of synaptic blockers inhibited the phosphorylation of p44/42 MAP kinase and reduced both the trypan-blue staining (n = 13) and the release of lactate dehydrogenase (n = 16) by 73% +/- 18% and 75% +/- 19% (mean +/- SD), respectively. The observed neuroprotection could be caused by an effect of PD098059 on seizure-like events or on downstream signaling pathways activated by the seizure-like events. Either possibility suggests a heretofore unknown function for the p44/42 MAP kinase pathway in neurons.

Animals↗
PubMed1998

An audit of pancreatic pseudocyst management and the role of endoscopic pancreatography.

BACKGROUND: A rational algorithm for the management of symptomatic pancreatic pseudocysts is necessary with the increasing availability of radiological, surgical and endoscopic methods of treatment. METHODS: A retrospective audit of the management and outcome of all patients who presented with symptomatic pancreatic pseudocysts to the Auckland Hospital over a 9-year period (1988-96) was made. RESULTS: There were 44 patients (28 men, 16 women; median age 50; range 18-81) in this series. Initial management was not based on pseudocyst size, duration, location, wall thickness, the patients' symptoms and comorbidity, or the aetiology of pancreatitis. Of the 27 patients who had initial conservative management, 15 pseudocysts (56%) completely resolved. Of the 17 patients who were initially or subsequently treated with percutaneous catheter drainage (PCD), 10 pseudocysts (59%) completely resolved without additional treatment. Of the 13 patients initially or subsequently treated by surgery, all but one completely resolved after the first procedure. Two patients were successfully treated with endoscopic pancreatic stent placement. Complications arose in eight patients treated with PCD (47%) and four patients treated with surgery (31%). There was no mortality. The decision for active treatment was not preceded by delineation of the pancreatic duct by ERCP (endoscopic retrograde cholangiopancreatography) in 60% of patients. CONCLUSIONS: More than one-third of all patients with symptomatic pancreatic pseudocysts can be managed conservatively. Surgery yields excellent results but PCD has a high failure rate in patients with an underlying pancreatic duct stricture. A rational management algorithm is presented, based on pre-intervention ERCP, which should improve patient selection and outcome.

Adolescent↗
PubMed1998

Studies of the continuing susceptibility of group A streptococcal strains to penicillin during eight decades.

BACKGROUND: In view of the widespread use of penicillin for >50 years for the treatment of group A streptococcal infections, we examined the question of whether there has been a change in susceptibility to penicillin in group A streptococcal strains collected during a span of 80 years (1917 to 1997). METHODS: One hundred thirty-three group A streptococcal strains collected during 80 years were tested for changes in penicillin susceptibility. Three tests were used: (1) the microtiter broth minimal inhibitory concentration (MIC); (2) the minimal bactericidal concentration (MBC); and (3) the penicillin E strip MIC. RESULTS: The results indicate there has been no change in the susceptibility to penicillin in these group A streptococci during the past 80 years. The microtiter broth MIC90 for the oldest strains (0.032 microg/ml) was not significantly different from those collected most recently (0.032 microg/ml); there is no statistical difference between the raw MIC data for the four collection periods (P=0.468, analysis of variance on ranks). CONCLUSIONS: There has been no change in the susceptibility of group A streptococci during this time in spite of well-documented cases of penicillin resistance in other Gram-positive organisms and despite recognized resistance of group A streptococci to other antibiotics.

Anti-Bacterial Agents↗
PubMed1997

Muscle patterning, differentiation and vascularisation in the chick wing bud.

Adult muscle is highly vascularised, with blood vessels being essential for adequate oxygenation of the tissue and for supporting increased metabolic demands. Whether this is the case during muscle development has not been examined. Resin histology was used to map the muscle splitting process and conventional transmission electron microscopy to examine early muscle differentiation at the midlimb level or later at the mid radius/ulna level in the chick wing bud from stages 24 (4.5 d) to 36 (10 d) (Hamburger & Hamilton, 1951). Microinjection of India Ink into the extra-embryonic vasculature was used to visualise the patent muscle microcirculation. The results showed that the premuscle masses are present at stage 24 and initial splitting of the muscle masses commences at stage 28. The final muscle pattern is not established until stage 36. At stage 26 the cells within the premuscle masses exhibited a mesenchymal morphology, but at stage 28 overt muscle differentiation was evident with myofibrils present within myoblasts. Undifferentiated mononucleated cells were interspersed with the differentiating myoblasts. The ratio of mononucleated cells:myoblasts decreased and the myoblasts became plumper and increasingly packed with myofibrils with age. There was no evidence of secondary myotube formation at any of the stages examined. Vascular invasion of the limb occurred at stage 35 just prior to the establishment of the final muscle pattern. This was surprising as it was assumed that myogenic differentiation would be both oxygen and nutrient dependent. The results of this study provide descriptions of the splitting of the premuscle masses through to the establishment of the final muscle pattern at the midlimb or mid radius/ulna level of the chick wing bud together with the differentiation of the myogenic cells within the developing muscles. However, the relationship between muscle patterning at the tissue level and muscle differentiation at the cellular level with vascularisation remains unclear. It is hoped that the results of the study may provide the basis for future investigations into mechanisms involved in muscle patterning and the signalling mechanisms for vascular invasion.

Animals↗
PubMed1997

Establishing a programme for continuous ambulatory infusion chemotherapy.

BACKGROUND: The development of venous access devices (VADs) and portable infusion pumps has enabled chemotherapy to be administered continuously within the home environment. AIM: The objective of this study was to describe the experience of establishing an ambulatory chemotherapy programme for patients receiving protracted infusions (PVIs) of 5-fluorouracil (5-FU). METHODS: The files of all patients receiving PVI 5-FU as a component of their treatment for gastrointestinal malignancy were reviewed. The types of VADs, infusion pump systems and their management were documented. Information packages and education programmes were developed for patients. RESULTS: Seventy-four patients with gastrointestinal cancer were studies. At the end of the period the Portacath was the preferred VAD, while both pumps used were found to have advantages and disadvantages. The choice of pump was decided more by patient preference than systematic differences in performance of the pumps. CONCLUSIONS: The findings in this review confirm that, with close attention to the potential pitfalls of ambulatory chemotherapy, an acceptable service can be provided.

Adult↗
PubMed1997

Linear accelerator photon beam quality at off-axis points.

Transmitted intensity through water was measured in a narrow-beam geometry for different energy x-ray beams from commercial accelerators. In order to accurately obtain the attenuation coefficient of the incident beam using transmission data, a novel formula was developed based on consideration of beam hardening in phantom. The value of the attenuation coefficient obtained by fitting transmission data to this formula was found to be independent of the absorber thickness used in experiments, whereas the attenuation coefficient obtained from the traditional formula, I(x) = I0 exp(-mux), changed by up to 7% with absorber thickness for a given beam. The beam hardening coefficient obtained from our formula indicates that the attenuation coefficient in water changes by about 0.33% per cm near the surface for the high-energy photon beams studied. Variations in beam quality with off-axis distance were subsequently investigated using the new formula. Results show that the attenuation coefficient at the water surface increased by about 15% for 15 and 18 MV beams, and by 11%-13% for 6 MV beams, when the off-axis distance at 100 cm from the source was changed from 0 to 18 cm. Consideration of the physics of bremsstrahlung production suggests that these variations should be mainly determined by the shape of the flattening filter, i.e., by the path length of rays traversing the filter in different directions. This expectation was confirmed by observing that the attenuation coefficient at the phantom surface can be related to the ray path of the beam in the flattening filter using the new transmission formula.

Biophysical Phenomena↗
PubMed1996

Physiological measures of conduction velocity and refractory period for putative reward-relevant MFB axons arising in the rostral MFB.

Extracellular recordings were obtained, in urethane-anesthetized rats, from 44 neurons in the rostral bed nuclei of the medial forebrain bundle (MFB). These cells were antidromically activated by stimulation of MFB sites that typically support self-stimulation. Recording sites included the magnocellular preoptic nucleus, substantia innominata, ventral pallidum, olfactory tubercle, and horizontal limb of the diagonal band. Refractory period estimates ranged from 0.35 to 1.20 ms (mean +/- SD = 0.72 +/- 0.30 ms, n = 15) for stimulation sites in the lateral hypothalamic and ventral tegmental areas when using currents of twice threshold and procedures designed to estimate excitability at or near the site of stimulation. Interelectrode conduction velocity estimates ranged from 1.48 to 20.0 m/s (mean +/- SD = 9.26 +/- 7.22 m/s, n = 11) and were obtained by dividing the interelectrode distance by the difference in the response latency from the two MFB stimulation sites. The refractory period and conduction velocity estimates for these neurons overlap the psychophysically derived estimates for MFB reward neurons. These data are consistent with the hypothesis that neurons arising in the rostral bed nucleus of the MFB compose at least part of the directly activated substrate for MFB self-stimulation.

Animals↗
PubMed1996

Attenuation of medical forebrain bundle reward by anterior lateral hypothalamic lesions.

Psychophysical data consistent with rostro-caudal conduction along reward-relevant neurons linking the lateral hypothalamus (LH) and ventral tegmental area (VTA) have lead to the hypothesis that some of the directly activated neurons responsible for medial forebrain bundle (MFB) self-stimulation arise anterior to the level of the LH. This hypothesis has been challenged on the grounds that lesions to the anterior LH (ALH) often fail to degrade the rewarding value of stimulating more posterior MFB sites. The present study was aimed at investigating the effect of lesion location and stimulation current on the efficacy of ALH lesions in an effort to account for the inconsistencies in the earlier data. Self-stimulation thresholds were obtained for LH and VTA sites by estimating the number of pulses per stimulation train required for half-maximal responding at each of 3 currents. Electrolytic lesions (anodal, 1.0 mA for 10 s) were then made to the ALH at varying medial-lateral coordinates. In 7 of the 14 rats with MFB stimulation sites, lesions to the ALH produced increases in threshold which often declined over the next several days to weeks; in 5 cases thresholds remained elevated by 0.1 to 0.25 log10 units above baseline up to end of testing. In all but one case, the effective lesions were centered in the lateral ALH. Increases in threshold were more likely to be detected when stimulating at low currents; at low currents fewer neurons are recruited and the lesion can have a greater proportional effect on threshold. These data support the hypothesis that cell bodies, terminals, or fibers of passage in the ALH contribute to the rewarding effect of stimulating more posterior MFB sites.

Animals↗
PubMed1996

Activated protein C resistance--low incidence in glaucomatous optic disc haemorrhage and central retinal vein occlusion.

PURPOSE: Activated protein C (APC) resistance has recently been reported as conferring a sevenfold increase in the risk of venous thrombosis. It is linked to a genetic mutation in the factor V gene which occurs commonly (about 2% to 4% of the community have the mutation). Glaucoma patients with nerve fibre layer (NFL) haemorrhages on the optic disc and patients with central retinal vein occlusion (CRVO) were tested for APC resistance to determine if there was an association. METHODS: Twenty-three patients with glaucomatous NFL haemorrhages and 23 patients with CRVO were tested. The CRVO cases included 11 with relatively young age of onset (mean 45.1 +/- 6.9 years) without conventional vascular risk factors. Eighty randomly selected Red Cross blood donor samples and 33 staff members were tested as controls. Clotting times with and without exogenous APC were recorded and an APC ratio determined. Cases with APC resistance were tested to confirm that they had the factor V Leiden gene. RESULTS: No cases of APC resistance were identified in the glaucoma patients and only one of the younger CRVO patients tested positive, but four of 113 controls tested positive. The difference in prevalence between groups is not significant. The mean APC ratios for the three groups were very similar: NFL haemorrhages 5.46(+/- 1.62), CRVO 5.70(+/- 1.56), controls 5.34 ( +/- 1.19) p > 0.5. CONCLUSION: There was not clear association detected between glaucomatous NFL haemorrhages or CRVO and APC resistance in this sample of patients. This negative finding is important due its known association with venous thrombosis elsewhere in the body.

Adult↗