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Biomedical subjects

A MacKinnon

Publications and source records attributed to A MacKinnon.

At least 19 recordsLinked to original sources

Direct observation of stimulated-Brillouin-scattering detuning by a velocity gradient.

We report the first direct evidence of detuning of stimulated Brillouin scattering (SBS) by a velocity gradient, which was achieved by directly measuring the frequency shift of the SBS-driven acoustic wave relative to the local resonant acoustic frequency. We show that in the expanding part of the plasma, ion-acoustic waves are driven off resonance which leads to the saturation of the SBS instability. These measurements are well reproduced by fluid simulations that include the measured flow.

Journal Article↗

Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder.

OBJECTIVES: The purpose of this study was to determine whether there are changes in the density of ionotropic glutamate receptors in the hippocampus of subjects with bipolar disorder. METHODS: Using in situ radioligand binding with semiquantitative autoradiography, we measured the density of [3H]MK-801, [3H]CGP39653, [3H]AMPA and [3H]kainate binding in hippocampi, obtained postmortem, from eight subjects with type 1 bipolar disorder and 8 age- and sex-matched controls. RESULTS: In subjects with bipolar disorder there were significant decreases in the density of [3H]MK-801 binding in the Cornu Ammonis (CA) 3 (mean +/- SEM; 108.8 +/- 12.2 versus 166.2 +/- 18.0 fmol/mg ETE, p < 0.005) as well as the pyramidal (102.8 +/- 9.2 versus 136.6 +/- 11.2 fmol/mg ETE, p < 0.05) and polymorphic (21.73 +/- 6.5 versus 53.26 +/- 11.6 fmol/mg ETE, p < 0.05) layers of the subiculum. In addition, two-way analysis of variance (ANOVA) revealed a decrease in the density of [3H]CGP39653 binding across the hippocampal formation in bipolar subjects, which did not reach significance in any subregion. There were no changes in the densities of [3H]AMPA or [3H]kainate binding in these subjects. CONCLUSIONS: [3H]CGP39653 and [3H]MK-801 bind to the glutamate binding site and open ion channel of the n-methyl-d-aspartate (NMDA) receptor, respectively. Therefore, these data suggest that there is a decrease in the number of open ion channels associated with no significant change in the apparent density of NMDA receptors in regions of the hippocampus from subjects with bipolar disorder.

Adult↗

Intense high-energy proton beams from Petawatt-laser irradiation of solids.

An intense collimated beam of high-energy protons is emitted normal to the rear surface of thin solid targets irradiated at 1 PW power and peak intensity 3x10(20) W cm(-2). Up to 48 J ( 12%) of the laser energy is transferred to 2x10(13) protons of energy >10 MeV. The energy spectrum exhibits a sharp high-energy cutoff as high as 58 MeV on the axis of the beam which decreases in energy with increasing off axis angle. Proton induced nuclear processes have been observed and used to characterize the beam.

Journal Article↗

Evaluation of predictive factors for neurocognitive dysfunction in patients with inactive systemic lupus erythematosus.

OBJECTIVE: To determine predictive factors associated with the cognitive dysfunction in patients with inactive systemic lupus erythematosus (SLE). METHODS: Consecutive patients followed at the Lupus Clinic with inactive SLE (SLE Disease Activity Index, SLEDAI, = 0) underwent a battery of neuropsychological tests; Beck Depression Inventory and psychiatric assessment were also performed. Neurocognitive dysfunction was defined as 3 abnormal scores. Data were analyzed using chi-square tests, ANOVA tests, and logistic regression. RESULTS: Twenty-five of the 58 patients with SLE (43%) versus 9 of 47 healthy controls (19%) demonstrated neurocognitive dysfunction (p < 0.01). Neurocognitive dysfunction was not associated with depression or a psychiatric diagnosis, use of steroids, or previous or current evidence for fibromyalgia. SLEDAI > 10 at first presentation to the Lupus Clinic and previous vasculitis were associated with neurocognitive dysfunction, but previous central nervous system disease, renal disease, renal damage, or atherosclerotic complications were not. Neurophysiologic studies at the time of the assessment were not predictive of neurocognitive dysfunction. CONCLUSION: Patients with inactive SLE demonstrate neurocognitive dysfunction. This is associated with more disease activity at presentation, but is not associated with specific organ involvement or organ damage.

Adult↗

Pattern of neuropsychologic dysfunction in inactive systemic lupus erythematosus.

The pattern of neuropsychological dysfunction in patients with inactive systemic lupus erythematosus (SLE) was examined. Fifty-eight subjects with inactive SLE and 47 healthy controls were administered a standardized neuropsychological test battery. Summary scores reflecting 18 different cognitive processes were derived. Subjects were designated cognitively impaired if three or more summary scores differed significantly from premorbid estimates of cognitive functioning. Cognitive impairment was identified in 43% of subjects with inactive SLE and 19% of healthy controls. Subjects with inactive SLE, as a group, performed significantly worse than healthy controls on measures of auditory verbal memory, visual spatial memory, psychomotor speed, and motor functioning. A significantly greater proportion of subjects with inactive SLE than healthy controls was impaired only on a measure of visual spatial memory. Cognitive impairment in subjects with inactive SLE was associated with increasing age. There were no associations between cognitive impairment and current depressive symptoms or current corticosteroid use. These findings suggest that cognitive dysfunction occurs frequently in inactive SLE. The variability of performance of subjects with inactive SLE is consistent with the heterogeneity of CNS involvement in the disease.

Adult↗

Fibromyalgia is a major contributor to quality of life in lupus.

UNLABELLED: OBJECTIVE; To determine whether individual variables of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Coordinating Committee/American College of Rheumatology (SLICC/ACR) Damage Index were associated with any of the domains of the Short Form 36 (SF-36) quality of life measure, and to assess the contribution of fibromyalgia (FM) to the quality of life measure. METHODS: Patients with systemic lupus erythematosus (SLE) seen between December 1994 and May 1995 completed SF-36 questionnaires at the time of their clinical evaluations at the Lupus Clinic. Disease activity was measured by SLEDAI, damage was assessed by the SLICC/ACR Damage Index, and FM was diagnosed in the presence of widespread pain and > or = 11 of 18 FM tender points. The components of SLEDAI and the Damage Index were compared to the domains of the SF-36 using Pearson correlation coefficients. A t test was used to compare the variables in patients with and without FM. RESULTS: One hundred nineteen patients with SLE participated in the study. Presence of FM, which occurred in 21% of the patients, was not related to either the overall scores or any of the components of SLEDAI or Damage Index, but was highly correlated with all 8 domains of the SF-36. The correlations ranged from -0.26 to -0.43, with associated p values of 0.007 to 0.0001. CONCLUSION: In a cross sectional study of patients with SLE at one point in time the SF-36 reflected the presence of FM rather than disease activity or damage.

Adult↗

Pore formation by S. aureus alpha-toxin in liposomes and planar lipid bilayers: effects of nonelectrolytes.

Nonelectrolytes such as polyethylene glycols (PEG) and dextrans (i) promote the association of S. aureus alpha-toxin with liposomes (shown by Coomassie staining) and (ii) enhance the rate and extent of calcein leakage from calcein-loaded liposomes; such leakage is inhibited by H+, Zn2+ and Ca2+ to the same extent as that of nonPEG-treated liposomes. Incubation of liposomes treated with alpha-toxin in the presence of PEG with the hydrophobic photo-affinity probe 3-(trifluoromethyl)-3-m-[125I]iodophenyl) diazirine (125I-TID) labels monomeric and-predominantly-hexameric forms of liposome-associated alpha-toxin; in the absence of PEG little labeling is apparent. At high concentrations of H+ and Zn2+ but not of Ca(2+)-all of which inhibit calcein leakage-the distribution of label between hexamer and monomer is perturbed in favor of the latter. In alpha-toxin-treated planar lipid bilayers from which excess toxin has been washed away, PEGs and dextrans strongly promote the appearance of ion-conducting pores. The properties of such pores are similar in most regards to pores induced in the absence of nonelectrolytes; the differ only in being more sensitive to "closure" by voltage (as are pores induced in cells). In both systems, the stimulation by nonelectrolytes increase with concentration and with molecular mass up to a maximum around 2,000 Da. We conclude (i) that most of the alpha toxin that becomes associated with liposome or planar lipid bilayers does not form active pores and (ii) that the properties of alpha-toxin-induced pores in lipid bilayers can be modulated to resemble those in cells.

Animals↗

Problem of diagnosis in postmortem brain studies of schizophrenia.

OBJECTIVE: The purpose of this study was to determine 1) the reliability of diagnoses of schizophrenia at coronal autopsy and 2) the degree to which the use of different diagnostic instruments for schizophrenia would affect postmortem brain research. METHOD: Eighty-three subjects, recorded at coronal autopsy as having had schizophrenia, were referred for neurochemistry studies. The diagnoses reported to the state coroner's office were reevaluated by a review of psychiatric case histories by clinicians using semistructured assessment and diagnostic criteria. RESULTS: The application of DSM-III-R, Research Diagnostic Criteria (RDC), ICD-10, Schneiderian, and Feighner criteria to the diagnosis of the 83 subjects revealed that 63.9%, 48.2%, 48,2%, 43.4%, and 42.2%, respectively, met the criteria for schizophrenia. Highest concordance was between the RDC and ICD-10 systems, while lowest concordance was between the RDC and Schneider systems. CONCLUSIONS: These data suggest that unless carefully reviewed, diagnosis may be a major confounding factor in postmortem studies of brain tissue from subjects with schizophrenia.

Adult↗

A comparison of five health status instruments in patients with systemic lupus erythematosus (SLE).

The aim of the present investigation was to assess and compare health status instruments in SLE. One hundred and twenty-five patients completed five health status instruments: the Health Assessment Questionnaire (HAQ), Functional Ability Index, the Fatigue Severity Scale (FSS), the Disability Days Measure (DDM), the Centre for Epidemiological Studies-Depression Scale (CES-D), and the Medical Outcomes Study (MOS) Short Form Health Survey during their Clinic visit. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). All instruments described a spectrum of quality of life outcomes in these patients. An inter-instrument correlation analysis revealed that components of the MOS correlated significantly with each of the other instruments used. There was no correlation between any of the instruments used and the SLEDAI. We conclude that health status assessment as measured by the MOS short form is a valid independent outcome measure in patients with SLE.

Adolescent↗

The relationship between the adrenoceptor and nonadrenoceptor-mediated effects of imidazoline- and imidazole-containing compounds.

This article brings together work on imidazoline or imidazole-containing compounds concerned with the pharmacology of alpha-adrenoceptors, principally on smooth muscle, to illustrate how imidazolines have contributed to the subclassification of alpha-adrenoceptors and how, against this background, attempts have been made to use this knowledge to uncover "nonadrenoceptor"-mediated biological effects of previously uncharacterized compounds, notably imidazole-containing dipeptides and "clonidine displacing substance" (CDS). Recent data are included on (1) the pharmacology of UK-14304, (2) nonadrenoceptor actions of phentolamine, (3) the pharmacology of tissue extracts containing imidazole-containing dipeptides and CDS activity, and (4) ligand binding data at I1 and I2 sites.

Animals↗

Evidence for the presence of a non-catecholamine, clonidine-displacing substance in crude, methanolic extracts of bovine brain and lung.

In the present study we have prepared crude, methanolic extracts of bovine lung and bovine brain and, using radioligand binding assays in conjunction with a number of simple chromatographic techniques, provided evidence for the presence of a non-catecholamine 'clonidine-displacing substance' (CDS). The level of CDS in lung extracts (9 units/g wet weight n = 11) is approximately 3 times that in the brain extracts. Furthermore, the effect of the crude, methanolic extracts are selective for non-adrenoceptor, imidazoline (labelled by [3H]-idazoxan) and alpha 2-adrenoceptor binding sites (labelled by [3H]-clonidine); both extracts are 5-10-fold more potent displacers of ligand binding to alpha 2-adrenoceptors compared with binding to opiate receptors (labelled by [3H]-etorphine) and practically inactive against alpha 1-adrenoceptor and muscarinic binding sites (labelled by [3H]-prazosin and [3H]-quinuclidinyl benzilate, respectively). With the exception of the non-adrenoceptor, imidazoline binding assay, which used rat kidney membranes labelled by [3H]-idazoxan in the presence of the alpha 2-adrenoceptor antagonist RS-15385-197, all radioreceptor assays involved bovine cerebral cortex membranes. Although the extracts contain catecholamines (brain only), histamine (lung only) and monovalent cations (both), which have the potential to interfere with the radioligand binding assays, their concentrations were too low to account for the effects observed. Preliminary attempts at purification of the extracts revealed that CDS activities from the two tissues are similar, i.e., practically insoluble in organic solvents at room temperature, not affected by either Sep-Pak C18 column or anion exchange resins but retained (along with the monovalent cations) by cation exchange resin. However, following chromatographic separation on a Biogel P2 column, the CDS-containing eluates are cation-free and exhibit qualitatively similar elution profiles. Future experiments will involve further purification of 'clonidine-displacing substance' to characterize its interaction with alpha 2-adrenoceptor binding sites in greater detail and establish whether it has biological activity consistent with the properties implied by its effects in radioligand binding assays.

Animals↗

The prevalence of depressive disorders and the distribution of depressive symptoms in later life: a survey using Draft ICD-10 and DSM-III-R.

The point prevalence of depressive disorders was estimated in a sample of persons aged 70 years and over, which included both those living in the community and those in institutional settings. Lay interviewers administered the Canberra Interview for the Elderly to the subjects and their informants. The point prevalence of depressive episodes as defined by the Draft ICD-10 diagnostic criteria was 3.3%. The rate for DSM-III-R major depressive disorder was 1.0%. The latter prevalence rate is similar to those reported elsewhere for the elderly. Evidence is accumulating that older persons may indeed have low rates for depressive disorders at the formal case level. Possible reasons for this finding are offered. A scale for depressive symptoms, based exclusively on those specified in Draft ICD-10 and DSM-III-R, showed that the elderly do experience many depressive symptoms. Contrary to expectation, these did not increase with age. The number of depressive symptoms was correlated with neuroticism, poor physical health, disability and a history of previous depression. Attention now needs to be directed to the clinical significance of depressive symptoms below the case level in elderly persons.

Age of Onset↗