Strangelet search and light nucleus production in relativistic Si+Pt and Au+Pt collisions.
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Journal Article↗
Biomedical subjects
J Lowe
Publications and source records attributed to J Lowe.
Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.
Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.
Dementia↗
Collecting and using student satisfaction data.
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Accreditation↗
In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity.
SR141716A has been described as a cannabinoid receptor antagonist. This study was conducted to determine whether SR141716A was capable of antagonizing the pharmacological effects of the prototypical cannabinoid agonist delta 9-THC. The AD50 (+/- 95% confidence limits) obtained after a 10 min i.v. pretreatment with SR141716A in measures of hypoactivity, hypothermia, and antinociception were: 0.12 (0.02-0.66), 0.087 (0.037-0.201), and 0.16 (0.03-1.01) mg/kg, respectively. The effect of SR141716A lasted up to 1 hr (antinociception, 10 mg/kg), 4 hr (locomotion, 1 and 3 mg/kg), or 24 hr (hypothermia, 3 mg/kg). Further evaluation revealed an AD50 value of 2.7 mg/kg (1.7-4.4) in the PPQ-stretch procedure. Additionally, the ED50 (+/- S.E.) of morphine in the tail-flick antinociception procedure was increased by SR141716A (30 mg/kg, i.v.) from 3.2 (+/- 0.3) to 5.3 (+/- 0.6) mg/kg. Finally, SR141716A produced direct effects on locomotor activity at doses greater than 3 mg/kg. Locomotion was stimulated to more than 200% of control (20 mg/kg), with an ED50 value of 4.7 (+/- 1.5) mg/kg. The ED50 value represents stimulation to levels approximately 150% of control. It is not clear whether this pharmacological activity represents an uncharacterized action of SR141716A, or an index of tonic activity of an endogenous cannabinergic system. SR141716A will be useful in establishing the biochemical events responsible for the in vivo effects of exogenous cannabinoids, as well as in establishing the existence of a putative endogenous cannabinergic system.
Analgesia↗
Allergen-induced histamine release in rat mast cells transfected with the alpha subunits of Fc epsilon RI.
A rat mast cell histamine assay (RMCHA) has been developed to quantitate the biological activity of a recombinant humanized, monoclonal anti-IgE antibody (rhuMAbE25). Rat mast cells (RBL 48), transfected with the alpha subunit of the high affinity human IgE receptor (Fc epsilon RI), were presensitized for 2 h with human plasma containing IgE specific for ragweed and challenged with ragweed allergen in the presence of 50% D2O. Histamine release plateaus at 0.1 micrograms/ml of ragweed. The release of histamine was time, temperature and Ca2+ dependent. This ragweed-induced histamine release could be inhibited by rhuMAbE25 in a dose-dependent fashion with an IC50 of 1.19 +/- 0.31 micrograms/ml (n = 25). Other humanized MAbs and recombinant human growth factors neither trigger histamine release nor inhibit ragweed-induced histamine release. This RMCHA correlates well with the human basophil histamine assay (HBHA) (Fei et al., 1994) with a correlation coefficient of 0.93 (n = 59, p < 0.0001). Histamine was also released when the cells were presensitized with human plasma containing the respective allergen-specific IgE and then challenged with standardized mite, D. farinae, house dust mix, standardized cat pelt, or Alternaria tenuis. Comparison of allergen-induced histamine release showed a good correlation between RMCHA and HBHA with a correlation coefficient of 0.69 (n = 37, p = 0.0001). We conclude that RMCHA provides a useful tool to confirm allergen-specific IgE in allergic patients and can be used to evaluate the biological activity of any anti-IgE monoclonal antibody. Moreover, RMCHA provides an unique opportunity to study the mechanism of IgE-mediated histamine release in the absence of interfering proteins and growth factors normally present in whole blood.
Allergens↗
Tau, ubiquitin, and alpha B-crystallin immunohistochemistry define the principal causes of degenerative frontotemporal dementia.
OBJECTIVE: We investigated the use of immunostaining with antibodies to tau, ubiquitin, and alpha B-crystallin in defining a protocol for the staged neuropathologic examination of brains from patients with a progressive frontotemporal dementia. DESIGN: Brains obtained from 50 patients dying with the clinical diagnosis of frontotemporal dementia were examined histopathologically to define pathologic distinctions. SETTING: Two university hospital neuropathology departments. RESULTS: Anti-tau immunostaining defined corticobasal degeneration, Alzheimer's disease, and Pick's disease; antiubiquitin defined motor neuron disease with dementia. The remaining brains have frontal lobe degeneration: the use of alpha B-crystallin immunostaining, on these, to detect ballooned neurons may help to define two groups of patients, one of which we believe may represent a variant of Pick's disease. CONCLUSION: These findings indicate that immunostaining with these antibodies is essential for the evaluation of frontal dementia.
Antibodies↗
Histomorphometric analysis of innervation of the anterior cruciate ligament in osteoarthritis.
The aim of this study was to determine whether there are quantitative changes in the innervation of the anterior cruciate ligament in osteoarthritis. Eleven whole anterior cruciate ligaments were obtained at autopsy from cadavera of individuals with advanced osteoarthritis: five healthy ligaments were used as controls. The ligaments were transected and stained with hematoxylin and eosin, oil red O for fat, and a modification of Gairn's gold chloride method. The latter stain permits visualization of axons, mechanoreceptors, and free nerve endings that are not apparent on routine stains. The ratio of nerve tissue to periligamentous synovial tissue was determined histomorphometrically by the point-counting method. The nerve tissue was located almost exclusively in the periligamentous synovial tissue. There was a statistically significantly greater area of nerve tissue (as a percentage of the total area) around the anterior cruciate ligaments in the osteoarthritic group than around the ligaments in the control group (p < 0.02). The nerve tissue was distributed evenly throughout the periligamentous synovial tissue in the specimens in both groups. A neurological role has been proposed for the anterior cruciate ligament in osteoarthritis. This study provides morphological evidence for neural pathology of the anterior cruciate ligament in subjects with osteoarthritis.
Adipose Tissue↗
Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues.
Ubiquitin cross-reactive protein (UCRP) is an interferon-inducible ubiquitin homologue which is constitutively present in cells and can be conjugated to other proteins. Using a characterized polyclonal antiserum to UCRP, immunohistochemical localization of UCRP was performed on paraffin-processed normal human tissues and in human tissues known to contain ubiquitinated intracellular inclusions. The antibody to UCRP immunostained lymphoid cells, striated and smooth muscle, several epithelia, and neurons. The level of staining varied greatly between tissues but was in a consistent punctate pattern. Localization to neuromuscular junctions and striations is similar to that described for antisera to ubiquitin-protein conjugates. Inclusion bodies characterized by immunoreactivity to anti-ubiquitin were not detected by the antibody to UCRP. Importantly, because UCRP may also be detected by antisera to conjugated ubiquitin, future studies on the distribution of ubiquitin in tissue sections must now take account of possible cross-reactivity with UCRP.
Cross Reactions↗
Parkinsonism in motor neuron disease: case report and literature review.
This report describes a patient who had clinical features of both motor neuron disease and Parkinson's disease. Neuropathological examination and immunocytochemical studies showed that he had motor neuron disease of the progressive muscular atrophy type, and Lewy body Parkinson's disease, with intracytoplasmic inclusion bodies characteristic of both conditions. This is the first detailed description of these two diseases occurring concurrently in the same patient. A review of all previously reported cases of combined motor neuron disease and parkinsonism has led to the following conclusions: (1) that these two neuropathologically defined diseases occur together very infrequently, but (2) that parkinsonism and substantia nigra degeneration are not uncommon as part of the multi-system disease process underlying motor neuron disease.
Aged↗
Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats.
CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in a number of studies as a radioligand for the cannabinoid receptor. This compound shares behavioral and biochemical properties with naturally occurring cannabinoids such as delta 9-THC. The purpose of the present study was 3-fold: to establish the ability of CP 55,940 to serve as a discriminative stimulus, to determine whether this discriminative stimulus is identical to that of delta 9-THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A, would antagonize the discriminative stimulus effects of CP 55,940. Rats were trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever operant conditioning chambers. CP 55,940 produced dose-dependent generalization from the training dose in dose-effect determinations conducted before and after testing with other drugs. The effects of the training dose of CP 55,940 were dose-dependently antagonized by co-administration of SR141716A. Results of substitution tests showed that delta 9-THC, WIN 55,212-2, and cannabinol substituted completely for CP 55,940 in a dose-dependent manner; however, CP 55,940 was approx 10-fold more potent than any of the other drugs in producing CP 55,940-like discriminative stimulus effects. Several drugs with CNS depressant properties (phencyclidine, haloperidol and diazepam) failed to produce reliable substitution for CP 55,940. These results demonstrate that CP 55,940 has discriminative stimulus effects and that it shares these effects with structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Analgesics↗
Search for H dibaryon-nucleus bound states in relativistic Au+Pt collisions.
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Journal Article↗
An anatomical, histological and magnetic resonance imaging study of the nasal septum.
Considerable variations are present in the thickness of the normal nasal septum. These were studied and measured in cadavers and from MRI scans. In addition, a histological analysis was performed to determine whether cavernous tissue is present at any point in the septum. The nasal septum reaches maximum thickness antero-superiorly where the mucosa may be as thick a 5.0 mm (average 3.5 mm) and the minimum thickness lies inferiorly where the mucosa is often thinner than 0.5 mm. The area of maximum septal thickness lies at the region of the nasal valve and its contribution towards nasal airway resistance must be significant. No cavernous tissue was identified in the nasal septum.
Adult↗
The cortical neuritic pathology of Huntington's disease.
We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Osmotic activation of a Na(+)-dependent Cl-/HCO3- exchanger.
In many systems, osmotically induced cell shrinkage activates the Na+/H+ exchanger. To assess the role of H(+)-extruding transporters in the response to osmotic shrinkage in vascular smooth muscle (VSM) and Chinese hamster ovary (CHO) cells, intracellular pH (pHi) was measured with 2',7'-bis(carboxy-ethyl)-5(6)- carboxyfluorescein-acetoxymethyl ester (BCECF-AM) after exposing cells to hypertonic medium. In nominally HCO(3-)-free medium, addition of 200 mM sucrose caused pHi to increase 0.33 pH unit on average in VSM cells but only 0.13 pH unit in CHO cells. Permeant solutes failed to increase pHi significantly. Cytochalasin B (1-20 microM), colchicine (1-10 microM), Ca2+ removal, and downregulation of protein kinase C activity did not affect osmotic activation of H+ extrusion in either cell type. Additional work was carried out to determine why osmotic activation of H+ extrusion was less in CHO than in VSM cells. In CHO cells, the osmotically induced delta pHi was only weakly sensitive to amiloride, suggesting that osmotic forces may activate an H+ transport system other than Na+/H+ exchange. In the presence of 10 mM HCO3-, osmotically induced delta pHi decreased by 60% in VSM cells but increased by 50% in CHO cells compared with the delta pHi in HCO(3-)-free medium. Lastly, removal of extracellular Cl- did not affect osmotically induced delta pHi in VSM cells but completely abolished the response in CHO cells. We conclude that in VSM cells osmotically induced changes in pHi are mediated by Na+/H+ exchange, whereas in CHO cells they are most likely mediated by a Na(+)-dependent Cl-/HCO3- exchanger.
Amiloride↗
Skeletal muscle lymphocytic vasculitis in systemic lupus erythematosus: relation to disease activity.
Lymphocytic vasculitis (LV) characterises systemic lupus erythematosus (SLE) and this potentially reversible lesion, which may be subclinical, may imply overt systemic disease activity. Needle quadriceps muscle biopsy was performed in 26 unselected patients with SLE and the presence of LV in these muscle specimens was compared with SLE disease activity scored using the British Isles Lupus Assessment Group Index (BILAG). Ten of the 22 patients with active disease showed evidence of LV compared with none of the four patients with inactive disease. In the patient group with LV, significantly higher ESR and urine neopterin values were found with P = 0.002 and P = 0.02, respectively compared with patients without LV. Features of vasculitis (as defined by BILAG) were also significantly more common in these patients (P = 0.005). None of the other parameters, including creatine kinase, were significantly different between the two patient subgroups. Thus, LV in needle quadriceps muscle biopsy specimens is a further valuable marker of disease activity in patients with SLE and might provide histological evidence of a systemic vasculitic process in a group of patients with diverse clinical manifestations.
Adult↗
Chicken B cells undergo discrete developmental changes in surface carbohydrate structure that appear to play a role in directing lymphocyte migration during embryogenesis.
The migration of progenitor cells to specific microenvironments is essential for the development of complex organisms. Avian species possess a unique primary lymphoid organ, the bursa of Fabricius, that plays a central role in the development of B cells. B cell progenitors, however, arise outside the bursa of Fabricius and, during embryonic development, must migrate through the vasculature to the bursa of Fabricius. In this report, we demonstrate that these progenitor B cells express the sialyl Lewis x carbohydrate structure previously shown to be a ligand for the selectin family of vascular adhesion receptors. Soon after migration to the bursa of Fabricius, B cell progenitors are induced to undergo a developmental switch and terminate the expression of sialyl Lewis x in a temporal pattern that correlates with the developmental decline in the ability of these cells to home to the bursa of Fabricius upon transplantation. The induction of the developmental switch in the glycosylation pattern of developing B cells requires the bursal environment. In addition, sialyl Lewis x carbohydrate determinants or structurally similar determinants on the surface of immortalized bursal lymphoid stem cells participate in the adherence of these cells to the vascular regions of the bursal microenvironment. These data demonstrate that the carbohydrate structure sialyl Lewis x is developmentally regulated during chicken B cell development and may facilitate the migration of B cell progenitors to the bursal microenvironment by serving as a ligand for a lectin-like adhesion receptor.
Animals↗
Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval.
OBJECTIVE: To investigate the time course of changes in follicular fluid (FF) concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal oocyte collection. STUDY DESIGN: Forty-five patients with tubal infertility were randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for sedation during ultrasound-guided transvaginal oocyte collection. Paracervical block with lignocaine was given for analgesia. Simultaneous blood and FF samples were drawn at 5-minute intervals after the bolus dose for analysis of drug levels. RESULTS: Data were obtained on 15 women receiving midazolam and fentanyl and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak and then fell in an exponential fashion as was expected. The FF levels of the agents continued to rise significantly to 25 minutes after the bolus dose, although the absolute level was low when compared with the blood level. There were no significant differences in fertilization or pregnancy rates in the three groups, but patient numbers were small. CONCLUSION: We conclude that midazolam, fentanyl, and alfentanil are found in FF after a single IV dose, but further investigation needs to be undertaken to investigate any potential influence on fertilization and implantation rates.
Adult↗