Search PubMed⌕ Search

Biomedical subjects

B McDonald

Publications and source records attributed to B McDonald.

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

Flatness characteristics for diagonal scans from Varian and Siemens linear accelerators.

The advent of 3D treatment planning systems whose algorithms utilize diagonal scan data to perform dose calculations has made the collection of diagonal profile data essential. Manufacturers' specifications (MS) on beam flatness and symmetry apply to both the radial and transverse axes of all square field sizes from 10 X 10 cm2 to the largest field available. Beam profile measurements were obtained for both diagonal axes over a range of field sizes and depths for two units, a Varian 2100C and a Siemens KD. In this note the International Electrotechnical Commission (IEC) flatness definition was used to characterize the diagonal flatness of each beam.

Humans↗
PubMed1996

Presynaptic serotonergic markers in community-acquired cases of Alzheimer's disease: correlations with depression and neuroleptic medication.

Presynaptic serotonergic markers, serotonin uptake sites, and concentrations of serotonin and 5-hydroxyindoleacetic acid were studied in the frontal and temporal cortex of 20 community-acquired cases of Alzheimer's disease and 16 controls matched for age, sex, postmortem delay, and storage. Clinical assessments, including behavioural symptoms, of the Alzheimer patients were made at 4-month intervals during life. There was significant reduction in the number of serotonin uptake sites in Alzheimer cases in temporal but not frontal cortex. There was no significant alteration in the concentrations of serotonin or 5-hydroxyindoleacetic acid in either region. Alzheimer patients who had persistent depressive symptoms during life had significantly fewer serotonin uptake sites in both cortical areas compared with Alzheimer patients without these symptoms. In addition, Alzheimer patients who were receiving chronic neuroleptic medication had significantly lower concentrations of serotonin in frontal cortex and 5-hydroxyindoleacetic acid in temporal cortex than those patients not receiving such treatment. These data suggest previous studies that reported uniform serotonergic dysfunction may have been subject to unintentional selection of behaviourally disturbed Alzheimer cases or those receiving chronic neuroleptic medication. This study also provides a basis for the treatment of behaviourally disturbed Alzheimer patients with serotonomimetics.

Age Factors↗
PubMed1996

Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.

Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT2C receptor (pEC50 = 7.80 +/- 0.06) compared with the 5-HT2A receptor (pEC50 = 7.30 +/- 0.08). Activation of the 5-HT2A receptor caused a transient fourfold increase in intracellular Ca2+ concentration. Whole-cell recordings of cells clamped at -50 mV demonstrated a small inward current (2 pA) in response to 10 microM 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT2C receptor, whereas activity at the 5-HT2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.

Adrenergic alpha-Agonists↗
PubMed1996

The palliative care quiz for nursing (PCQN): the development of an instrument to measure nurses' knowledge of palliative care.

This paper describes the process and outcomes of a study to develop a tool to measure nurses' knowledge of palliative care. The development of the palliative care quiz for nursing (PCQN) entailed the convening of an advisory committee, a wide process of consultation, the development of a conceptual framework, determination of format, generating of items and pre-testing, piloting and further testing of the quiz. The PCQN is a 20-item true, false and 'I don't know' test of knowledge that is easily administered and has utility for assessing knowledge, stimulating discussion and identifying misconceptions about palliative care nursing.

Education, Nursing↗
PubMed1995

The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins.

To help account for the variable quality and quantity of RNA in human brain, we have studied the effect of premortem (agonal state) and postmortem factors on the detection of poly(A)+mRNA and eight mRNAs. For comparison, the influence of the same factors upon gene products encoded by the mRNAs was studied immunocytochemically or by receptor autoradiography. Brain pH declined with increasing age at death and was related to agonal state severity, but was independent of postmortem interval and the histological presence of hypoxic changes. By linear regression, pH was significantly associated with the abundance of several of the RNAs, but not with poly(A)+mRNA, immunoreactivities, or binding site densities. Postmortem interval had a limited influence upon mRNA and protein products. Freezer storage time showed no effect. Parallel rat brain studies showed no relationship between postmortem interval (0-48 h) and amounts of total RNA, poly(A)+RNA, or two individual mRNAs; however, RNA content was reduced by 40% at 96 h after death. pH is superior to clinical assessments of agonal state or mode of death in predicting mRNA preservation. It provides a simple means to improve human brain gene expression studies. pH is stable after death and during freezer storage and can be measured either in cerebrospinal fluid or in homogenised tissue.

Acidosis↗
PubMed1995

Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages.

Nitric oxide (NO) is produced by numerous different cell types, and it is an important regulator and mediator of many processes including smooth muscle relaxation, neurotransmission, and murine macrophage-mediated cytotoxicity for microbes and tumor cells. Although murine macrophages produce NO readily after activation, human monocytes and tissue macrophages have been reported to produce only low levels of NO in vitro. The purpose of this study was to determine if stimulated human mononuclear phagocytes produce inducible nitric oxide synthase (iNOS) mRNA, protein, and enzymatic activity. By reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we show that human monocytes can be induced to express iNOS mRNA after treatment with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma). By immunofluorescence and immunoblot analyses, we show monocytes and peritoneal macrophages contain detectable levels of iNOS antigen after stimulations with cytokines in vitro. Control monocytes or those cultured with LPS and/or various cytokines have low levels of NOS functional activity as measured by the ability of cell extracts to convert L-arginine to L-citrulline, and they produce low levels of the NO catabolites nitrite and nitrate. Peritoneal macrophages have significantly enhanced nitrite/nitrate production and NOS activity after treatment with LPS and/or IFN-gamma, whereas monocyte nitrite/nitrate production and NOS activity are not altered by the treatments. Monocytes cultured with various live or heat-killed bacteria, fungi, or human immunodeficiency virus (HIV)-1 do not produce high levels of nitrite/nitrate. Antibodies against transforming growth factor-beta (TGF-beta), a factor known to inhibit iNOS expression and NO production in mouse macrophages, do not enhance NO production in human monocytes or macrophages. Biopterin, an obligate cofactor of iNOS enzymatic activity, is undetectable in freshly isolated or cultured human monocytes and peritoneal macrophages. However, replenishment of intracellular levels of tetrahydrobiopterin by culture with the cell-permeable, nontoxic precursor sepiapterin does not enhance the abilities of the human mononuclear phagocytes to produce NO in vitro. Mixing experiments show no evidence of a functional NOS inhibitor in human mononuclear phagocytes. Thus, we demonstrate that human mononuclear phagocytes can produce iNOS mRNA and protein, and (despite this) their abilities to generate NO are very low.

Amino Acid Oxidoreductases↗
PubMed1995

Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia.

Schizophrenia is associated with a complex pattern of alterations in the glutamatergic system of the brain. Previous studies have shown a reduced density of some hippocampal non-N-methyl-D-aspartate (non-NMDA) receptors which is accompanied by a loss of encoding receptor mRNA. We have extended this work using in situ hybridization histochemistry with oligonucleotide probes specific for two non-NMDA receptor transcripts, GluR1 and GluR2, in right and left medial temporal lobe sections from 9 schizophrenics and 14 matched normal controls. Both mRNAs were found to be decreased bilaterally and to a similar degree in the hippocampal formation in schizophrenia. Analysis of autoradiograms showed a regional loss of GluR1 and GluR2 mRNAs in dentate gyrus, CA4, CA3 and subiculum. GluR2 mRNA was also reduced in parahippocampal gyrus. These reductions ranged from 25% to 70% in terms of 35S nCi/g tissue equivalents. Additionally we measured grain density for the mRNAs over individual pyramidal neurons in each area. GluR1 and GluR2 mRNAs were less abundant per neuron in CA4 and CA3 in schizophrenia than in controls. GluR2 mRNA was also reduced significantly in parahippocampal gyrus neurons, with an increase in the proportion of GluR1 mRNA to GluR2 mRNA in this cell population. No asymmetries in expression of GluR1 and GluR2 were found in normal or schizophrenic brains. These data further the evidence for reduced non-NMDA receptor expression in the medial temporal lobe in schizophrenia. They confirm the decrease in GluR1 mRNA and show that there are similar losses of GluR2 mRNA in the hippocampal formation. The pattern of changes in the two mRNAs suggests a common mechanism which is unknown but which may be a correlate of the neurodevelopmental abnormalities postulated to underlie the disease. The reduction of GluR2 mRNA but not GluR1 mRNA in parahippocampal gyrus neurons in schizophrenia may have functional consequences given the calcium permeability of non-NMDA receptors lacking the GluR2 subunit.

Adult↗
PubMed1995

Myelinated axon number in the optic nerve is unaffected by Alzheimer's disease.

AIMS/BACKGROUND: Visual symptoms are a common but not invariable feature of Alzheimer's disease (AD) and such symptoms appear to become more pronounced as the severity of the dementia increases. Pathology in both the pregeniculate and cortical parts of the visual system has been suggested to underlie the visual deficits in AD. In order to investigate the former possibility, the effect of AD on the optic nerve was investigated. METHODS: Intraorbital segments of optic nerve were taken at autopsy from nine patients with AD and seven patients with no history of psychiatric or neurological disease and no abnormal neuropathology. All patients had functional vision before death and appeared free of retinal, optic nerve, or microvascular disease. The optic nerves were processed into resin, semi-thin sections cut perpendicular to the long axis of each optic nerve, and stained with paraphenylenediamine. The sections were then investigated using an image analysis system and standard morphometric techniques. RESULTS: There was no significant difference in the mean cross sectional neural area of AD compared with control optic nerves. Neither were there any significant differences between myelinated axon surface density, total axon number, or mean cross sectional axon area in AD compared with control optic nerves. CONCLUSION: These results indicate that optic nerve degeneration is not a feature of AD and suggest that the visual deficits in the disease result from cortical dysfunction. This view is supported by the fact that visuospatial dysfunction appears to be the most common visual problem in AD.

Aged↗
PubMed1995

Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease.

The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Poor eyesight contributes to the severity but not the persistence of the hallucinations.

Aged↗
PubMed1994

Rapidly progressing atrophy of medial temporal lobe in Alzheimer's disease.

The symptoms of Alzheimer's disease are associated with pathological change and loss of neurons in the medial temporal lobe. By yearly temporal-lobe-oriented computed tomograms the average rate of atrophy of the medial temporal lobe was 15.1% per year (95% CI 10.0, 20.2) in 20 patients with histopathologically, confirmed Alzheimer's disease and 1.5% (0.2, 2.8) in 47 healthy ageing controls. Such excessive atrophy presumably reflects the vulnerability of the medial temporal lobe to a catastrophic event, probably a pathological cascade process. Thus, Alzheimer's disease may not be due simply to an acceleration of normal ageing but, rather, is the consequence of a true disease process.

Aged↗
PubMed1994

Comparison of the phosphorylation of microtubule-associated protein tau by non-proline dependent protein kinases.

Microtubule-associated protein tau from Alzheimer brain has been shown to be phosphorylated at several ser/thr-pro and ser/thr-X sites (Hasegawa, M. et al., J. Biol. Chem. 267, 17047-17054, 1992). Several proline-dependent protein kinases (PDPKs) (MAP kinase, cdc2 kinase, glycogen synthase kinase-3, tubulin-activated protein kinase, and 40 kDa neurofilament kinase) are implicated in the phosphorylation of the ser-thr-pro sites. The identity of the kinase(s) that phosphorylate the ser/thr-X sites are unknown. To identify the latter kinase(s) we have compared the phosphorylation of bovine tau by several brain protein kinases. Stoichiometric phosphorylation of tau was achieved by casein kinase-1, calmodulin-dependent protein kinase II, Gr kinase, protein kinase C and cyclic AMP-dependent protein kinase, but not with casein kinase-2 or phosphorylase kinase. Casein kinase-1 and calmodulin-dependent protein kinase II were the best tau kinases, with greater than 4 mol and 3 mol 32P incorporated, respectively, into each mol of tau. With the sequential addition of these two kinases, 32P incorporation approached 6 mol. Peptide mapping revealed that the different kinases largely phosphorylate different sites on tau. After phosphorylation by casein kinase-1, calmodulin-dependent protein kinase II, Gr kinase, cyclic AMP-dependent protein kinase and casein kinase-2, the mobility of tau isoforms as detected by SDS-PAGE was decreased. Protein kinase C phosphorylation did not produce such a mobility shift. Our results suggest that one or more of the kinases studied here may participate in the hyperphosphorylation of tau in Alzheimer disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Synaptophysin gene expression in human brain: a quantitative in situ hybridization and immunocytochemical study.

Synaptophysin is a presynaptic vesicle protein. Its quantitative detection has become established as a molecular marker of synaptic density. We have studied synaptophysin messenger RNA in the neocortex, hippocampus and cerebellum using in situ hybridization histochemistry to see if the encoding transcript can be detected in post mortem human brain and to investigate factors which might influence its abundance. Synaptophysin was also measured immunocytochemically in the hippocampus. The level of synaptophysin messenger RNA expression was uniform in all neocortical areas examined. Strong correlations were found for the amount of synaptophysin messenger RNA between individual regions and between homologous areas in the two hemispheres. Synaptophysin messenger RNA declined with increasing age and prolonged post mortem interval. Synaptophysin immunoreactivity also reduced with age, as well as with duration of formalin fixation but not post mortem interval. Synaptophysin immunoreactivity correlated with the abundance of the messenger RNA in neurons within, and projecting to, each hippocampal subfield. Significantly greater synaptophysin immunoreactivity was seen in the left than the right CA4 and CA1 regions. These data show that quantitative detection of synaptophysin messenger RNA as well as synaptophysin itself can reliably be carried out in post mortem human brain sections. They are in keeping with other findings that synaptic density is relatively uniform through the neocortex and decreases with age. They also suggest a possible asymmetry of hippocampal synaptophysin expression. The level of synaptophysin messenger RNA paralleled that of synaptophysin immunoreactivity, indicating that changes in gene expression contribute to variations in the latter observed in aging and other situations. Detection of synaptophysin messenger RNA broadens the range of methods by which synaptic protein gene products can be studied and used as markers of synaptic density and synaptic involvement during physiological and pathological processes in human brain.

Adult↗
PubMed1994

Providing palliative care to older adults: context and challenges.

This paper presents the findings of a study aimed at understanding more fully the work of nurses who provide care to older adults who are dying at home. The method employed was qualitative in nature and involved the use of focus groups for data collection. Data were gathered from a total of 40 community-based nurses during four sessions lasting approximately two hours each. Analysis revealed that the provision of care occurred within a context of aging and dying characterized by clients' awareness of impending death, the presence of multiple pathologies, diminishing social support, and a lack of control. Challenges to providing care stemmed from an ethic of high expectation and a health care system experienced as fragmented, bureaucratic, and driven by cost efficiency. Challenges included working in isolation, achieving closure, securing personal support, working collaboratively with others, and keeping up to date. Findings from this study have implications for both education and practice.

Aged↗
PubMed1993

Glyceraldehyde-3-phosphate dehydrogenase is required for the transport of nitric oxide in platelets.

Nitric oxide (NO) or NO-generating compounds like sodium nitroprusside (SNP) increase cellular levels of cGMP and produce S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase [GAPDH; D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12]. In search of a reagent that could discriminate between these two effects, we used the sesquiterpene antibiotic koningic acid, which binds to GAPDH at the Cys-149 of the active site. Koningic acid inhibited basal and sodium nitroprusside-stimulated NAD-dependent covalent modification of purified rabbit muscle GAPDH in a dose-dependent manner. Furthermore, we tested the effect of koningic acid on human platelets. Approximately 90% of GAPDH is present in the cytosol of human platelets, and the exposure of platelet cytosol to koningic acid inhibited GAPDH activity, while the soluble guanylyl cyclase (basal and sodium nitroprusside-stimulated) activity remained unaltered. Pretreatment of intact platelets with koningic acid slowed the rate of aggregation induced by a submaximal concentration of thrombin. In addition, the antibiotic also inhibited the cGMP increases triggered by SNP, S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosyndomidine (SIN-1) but failed to prevent an increase in cGMP caused by nitrosylated albumin. Under the same conditions, koningic acid also inhibited basal and SNP- SNAP-, and SIN-1-stimulated NAD-dependent modification of GAPDH and its enzymatic activity. These results suggest that the mechanism of delivery of NO from SNP, SNAP, and SIN-1 to platelets may require the active form of GAPDH. When NO is delivered by nitrosylated albumin, active GAPDH was not necessary.

Biological Transport↗