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Biomedical subjects

M Bruce

Publications and source records attributed to M Bruce.

At least 19 recordsLinked to original sources
PubMed1992

Anxiogenic effects of caffeine in patients with anxiety disorders.

The effects on measures of anxiety from two doses of oral caffeine (250 and 500 mg) and placebo were compared in 12 patients with generalized anxiety disorder (GAD), 12 patients with panic disorder, and 12 normal subjects. Caffeine produced significantly less decrease in electroencephalographic alpha wave activity, greater decrease in N1-P2 auditory evoked potential amplitude, and greater increased in skin conductance level, systolic and diastolic blood pressure, critical fusion flicker frequency, and self-ratings of anxiety and sweating in patients with GAD than in normal patients. Patients with panic disorder showed different reactivity than normal patients did with respect to electroencephalographic alpha waves, N2 latency, N2-P2 auditory evoked potential amplitude, and physical tiredness but were less reactive than patients with GAD on several variables. It is concluded that patients with GAD are abnormally sensitive to caffeine and that the data support the view that panic disorder is a separable disorder from GAD.

Alpha Rhythm↗
PubMed1992

Arthropod toxins as leads for novel insecticides: an assessment of polyamine amides as glutamate antagonists.

In the search for new toxins, preferably with new sites of action, the polyamine amides represent a new class of compounds with potential as insecticides and as pharmaceutical agents due to their antagonism of ligand-gated cation channels. In particular, they are potent antagonists of the L-glutamate receptors of insect skeletal muscle. In this paper, we report on synthetic studies to produce hybrid analogues based upon the argiotoxin spider toxins and philanthotoxin-433 which is obtained from a solitary, parasitic wasp. We speculate upon possible modes and sites of action for these antagonists and we discuss their potential as insecticides and in the possible treatment of ischaemic damage. The synthesis and characterization of 4-hydroxyphenylpropanoylspermine is reported and the locust muscle biological assay is described. Using this pharmacological screen, structure-activity relationships have been determined in our laboratories. These are reviewed in the light of the current literature. Voltage clamp studies of the synthetic analogue philanthotoxin-343 and the effects of this polyamine amide on glutamate receptors expressed in Xenopus oocytes are outlined. In conclusion, a description of our current ideas and understanding of the many sites and modes of action of the polyamine amides, based both upon our own studies and also upon those recently reported, is presented.

Animals↗
PubMed1991

Synaptophysin and chromogranin A immunoreactivities in senile plaques of Alzheimer's disease.

Immunolabelling for synaptophysin and chromogranin A, two polypeptides associated with small clear and large dense core synaptic vesicles respectively, has been performed on tissue sections of the temporal cortex in Alzheimer's disease in combination with anti-A4 amyloid labelling. The dystrophic neurites in many senile plaques were observed to be labelled by the anti-synaptophysin or anti-chromogranin A antibodies. Some diffuse amyloid deposits, demonstrated by antibodies against synthetic amyloid A4 peptides, were associated with a punctuate increase in synaptophysin or chromogranin A immunoreactivity. The labelling of dystrophic plaque neurites may reflect the accumulation in these processes of synaptic vesicles or material derived from them. We suggest also that the punctuate increase in synaptophysin and chromogranin A immunoreactivities associated with some A4 amyloid deposits may be an early event reflecting neuronal dysfunction.

Alzheimer Disease↗
PubMed1991

Beta amyloid precursor protein mediates neuronal cell-cell and cell-surface adhesion.

The beta-amyloid precursor protein (APP) is a membrane-bound glycoprotein which has been proposed to play a role both as a growth factor and a mediator of cell adhesion. Using the Neuro-2A neuroblastoma cell line, we have investigated the capacity of APP to mediate neural cell adhesion. The cells express the protein at a high level, the immunohistochemical staining pattern at the level of the membrane having a punctate pattern. Fab' fragments of antibodies to the extracellular portion of the molecule were found to inhibit cell binding to a collagen substrate, but not to laminin, fibronectin, or poly-l-lysine. Fab' fragments of antibodies to the nerve cell adhesion molecule N-CAM also inhibited binding of Neuro-2A cells specifically to collagen. This inhibition of cell-surface binding was accompanied by a repression of neurite outgrowth in differentiating cells in the presence of antibodies. APP antibodies also inhibited neuron-neuron and neuron-glial binding, but not glial-glial cell adhesion. These data suggest that the APP, which is expressed primarily on differentiated neuronal cells, may play a role in the mediation of both cell-cell and cell-substrate adhesion.

Amyloid beta-Peptides↗
PubMed1990

Antibodies raised against different portions of A4 protein identify a subset of plaques in Down's syndrome.

Antisera were raised to peptides corresponding to residues 1-10 and 12-28 of the published sequence of A4 protein, a 42/43 amino acid long peptide isolated from the brains of patients with Down's syndrome and Alzheimer's disease. Immunohistochemical studies performed on sections of temporal lobe from 12 cases of Down's syndrome showed that the number of senile plaques in the molecular layer of the dentate gyrus which were identified by antibody to A4(1-10) was only 23% (range 11-53%) of that recognised by antibody to A4(12-28). This observation has important consequences for both the diagnosis and the pathogenesis of Down's syndrome and Alzheimer's disease.

Adult↗
PubMed1990

Ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice.

Sections of brain from normal mice or clinically-ill mice infected with either the 87V or the ME7 strains of sheep scrapie were immunostained to show the localization of ubiquitin-protein conjugates or a specific marker of disease, the scrapie-associated fibril protein (PrP). In both scrapie models immunoreactive ubiquitin-protein conjugates were seen in thread-like structures found throughout the neuropil, in inclusion bodies within vacuolated neurones, and in areas surrounding anti-PrP positive amyloid plaques. The PrP protein was visualized in diffuse deposits in highly vacuolated parts of the scrapie-affected brain, and focally in amyloid plaques, microglia and neuronal processes. The ubiquitin-protein conjugate staining of scrapie amyloid plaques is very similar to that seen in the plaques of Alzheimer's disease. The ubiquitinated intraneuronal inclusion bodies seen in scrapie resemble the granulovacuolar lesions also seen in Alzheimer's disease, but appear much larger and possibly correspond to material in giant autophagic vacuoles. We suggest that these inclusions may be the result of ubiquitinated abnormal proteins being directed to the lysosomal system, and that scrapie and Alzheimer's disease share at least some common processes of neurodegeneration.

Amyloid↗
PubMed1990

Structure-activity relationships of analogues of the wasp toxin philanthotoxin: non-competitive antagonists of quisqualate receptors.

Fifty-two analogues of the wasp toxin, philanthotoxin-433, have been synthesized and tested on a glutamatergic, nerve-muscle preparation from locust leg. Reduction in amplitude of the neurally-evoked muscle twitch was used to construct dose-inhibition relationships from which IC50S were estimated. The most active analogues were characterized by one or more of the following: increased hydrophobicity of aromatic and tyrosyl regions; an increased number of protonated groups in the polyamine region; a guanidinium instead of a spermine terminal amino moiety. The incorporation of a butyl side-group in the polyamine also enhanced potency. These results are explained on the basis of the known non-competitive antagonistic blockage by philanthotoxin-433 of the channel gated by postjunctional glutamate receptors when the channel is open.

Animals↗
PubMed1990

The preservation of red cell antigens at low ionic strength.

Low-ionic-strength saline (LISS) techniques permit a safe and substantial reduction in incubation time and have therefore become the method of choice for antibody detection and compatibility testing in many transfusion laboratories. Consequently, the supply of reagent red cells (RBCs) in a low-ionic-strength preservative solution would remove the daily need for laboratories to wash and resuspend cells in LISS before use. However, the storage of fresh RBCs at low ionic strength in the presence of aminoglycoside antibiotics can cause a rapid loss of certain antigens, possibly as a result of the release of proteolytic enzymes from contaminating white cells. This article describes a low-ionic-strength solution that achieves preservation of antigens on liquid nitrogen-frozen-thawed RBCs for 21 days' storage at 4 degrees C.

Blood Preservation↗
PubMed1990

Slip-shod or safely shod: the bighorn sheep as a natural model for research.

Over a million injuries caused by slipping of footwear are believed to require treatment by doctors every year in the United Kingdom and many domestic animals are injured by slipping. Recent research has revealed that surface roughness of solings and floors is an important determinant of grip on lubricated surfaces and it is also known that soling friction is affected by hardness. The bighorn sheep (Ovis canadensis) an animal species which has adapted to a slippery environment, was studied to elucidate optimum roughness and hardness and other features which influence grip. Four adult ewes were examined in the London Zoo. The cloven hooves of this species are very mobile and the cranial tips of the hooves are the first parts to make contact with the ground. A very small contact area ensures penetration of a film of water. Mean roughness of the contact area was found to be 53 microns Rtm and the mean hardness 63 Shore A. These characteristics appear to facilitate an excellent grip on wet slippery rock but not on smooth ice. Further studies of the feet of wild species could contribute to an understanding of the factors which determine the safety of solings and floors.

Accident Prevention↗
PubMed1990

Granulocyte transfusions in septic adult and newborn rats: distribution of granulocytes and effect on peripheral blood and bone marrow.

Granulocyte transfusions are increasingly being used as therapy for newborns with sepsis and neutropenia. We injected either group B Streptococcus or phosphate-buffered saline solution intraperitoneally into adult and newborn rats. Human granulocytes, labeled with chromium 51, were transfused seven hours later. When the newborn rats were killed 13 to 19 hours after injection, they had 10(2) to 10(6) cfu/gm Streptococcus organisms in both lung and brain. Only one third of the adult rats had 10(2) to 10(4) cfu/gm Streptococcus organisms in either lung or brain. A greater proportion of the transfused granulocytes was present in lung and brain tissue of newborn rats, compared with adult rats (p less than 0.05), irrespective of infection. Granulocyte transfusion did not change the peripheral blood leukocyte count in adult rats but increased the count in newborn rats (p less than 0.05). The immature myeloid pool in the bone marrow of adult rats increased significantly with either infection or transfusion (p less than 0.01). The immature pool in newborn rats increased significantly only with infection (p greater than 0.001), although the combination of infection and transfusion also had a significant effect on the pool (p less than 0.01). Infection and both infection and transfusion, but not transfusion alone, significantly affected the mature myeloid bone marrow pool in adult and newborn rats (p less than 0.001). The depletion of the mature myeloid elements of the bone marrow in response to infection was dramatic in neonatal rats, compared with that in adult rats. Both transfused granulocytes and hematogenously spread streptococci lodge in the brains and lungs of neonatal rats more effectively than in those of adult rats.

Age Factors↗
PubMed1988

Cerebrovascular amyloid in scrapie-affected sheep reacts with antibodies to prion protein.

In an immunohistochemical study of naturally-occurring and experimental scrapie in sheep, deposits of cerebrovascular amyloid were found to react with antibodies to hamster scrapie prion protein (PrP 27-30), but not with antibodies to the amyloid beta-protein of Alzheimer's disease. It is concluded that this vascular amyloid is formed from PrP and is therefore closely associated with scrapie infection. It is likely that this amyloid is formed from a host precursor protein as a specific pathological consequence of invasion by the scrapie agent.

Amyloid↗
PubMed1988

LKE red cell antigen and its relationship to P1 and Pk: serological study of a large family.

The fourth example of human anti-LKE was identified in the serum of an antenatal patient. Study of the red cells of the proband and her family confirmed the recessive inheritance of the LKE- phenotype. The blood groups of the family confirmed that Pk expression is greater on cells from LKE- members than on those from LKE+ members. In this family, the expression of LKE varied with the P1 phenotype. LKE- individuals occurred with an incidence of 0.0017 in the donor population of the Glasgow and West of Scotland Region.

Blood Group Antigens↗
PubMed1988

Inheritance and linkage data for an unusual combination of genes (at the LKE, PI and C6 loci) in a single large sibship.

Analysis of the groups of a large sibship showed that the locus for the blood group LKE is not closely linked to the loci for MNS, Rh, HLA, Pi, Gm and C6 and is genetically independent of the loci for P1, K, Xg, Au, secretor, and C3. The locus for the Auberger (Au) blood group was shown to be genetically independent of the locus for the blood group Kell and of the loci for C3, C6, Gc, HLA, Pi and Gm groups.

Blood Group Antigens↗
PubMed1987

Oral glucose tolerance and ambient temperature in non-diabetic subjects.

When either a 960-kcal, 140-g carbohydrate meal, or a 75-g glucose load was ingested by non-diabetic Caucasians, the 2-h venous plasma glucose concentration was higher by 0.82 and 1.25 mmol/l, respectively, if the ambient temperature was 33 degrees C rather than 23 degrees C. It is likely that this is a result of relative 'arterialisation' of the venous blood. Even at 23 degrees C room temperature, use of the 'hot hand' technique to obtain 'arterialized' venous blood increases post-load glucose levels in contralateral antecubital veins. If these observations apply to those acclimatised to the heat, they could affect the diagnosis of both diabetes and impaired glucose tolerance in the tropics.

Adult↗
PubMed1986

The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and caffeine metabolites in plasma and urine were assayed. Peak plasma concentrations were observed at 1 to 2 h with an approximate half-life of 5 h. The concentrations of the metabolite 1,7-dimethylxanthine increased during the 5 h. The major urine metabolite was 1-methyluric acid. The EEG showed a dose-related decrease in log 'theta' power and a decrease in log 'alpha' power. Other dose-related effects were an increase in skin conductance level (sweat-gland activity) and self rating of alertness. Ratings of headache and tiredness were decreased by the caffeine. The study illustrates the complexities of studying a drug which is widely taken and which is often associated with withdrawal effects.

Administration, Oral↗
PubMed1986

States of anxiety and their induction by drugs.

Syndromes of anxiety include generalized anxiety states, various forms of phobic disorder and panic attacks. It is unclear whether panic attacks are a separate syndrome from anxiety states or a more severe form. Drug-induced states of anxiety should provide useful models of the mechanisms of anxiety and its treatment. High-risk populations might be identifiable. Catecholamine infusions produce marked peripheral changes without fully reproducing the central feelings. Lactate infusions also produce anxiety-like states lacking full credibility. Experience with the benzodiazepine-receptor contragonists, the beta-carbolines, is limited but panic states have been reproduced following their use. Caffeine produces an anxiety state in high dose and some panic states have been induced. The critical evaluation of drug-induced anxiety states is a promising way of elucidating the mechanisms, psychological and physiological, associated with clinical anxiety.

Animals↗