Search PubMed⌕ Search

Biomedical subjects

E Armstrong

Publications and source records attributed to E Armstrong.

At least 73 records · Page 4Linked to original sources

Site-specific water proton relaxation enhancement of iron(III) chelates noncovalently bound to human serum albumin.

Binding of potential blood pool and hepatobiliary paramagnetic iron(III) contrast agents, rac- and meso-Fe(5-Br-EHPG)- (iron(III) N,N'-ethylenebis [(5-bromo-2-hydroxyphenyl)glycinate]) and Fe(5-Br-HBED)- (iron(III) N,N'-bis-(5-bromo-2-hydroxybenzyl)ethylenediaminediacetic acid) to human serum albumin (HSA) has been studied using the proton relaxation enhancement (PRE) effect on solvent protons. These chelates bind avidly to multiple sites on HSA with binding constants on the order of 10(4) to 10(5) M-1. Interestingly, binding results in a decrease in the diamagnetic component of the water relaxivity due to HSA, while the expected enhancement of the paramagnetic component of water proton relaxation rates occurs due to the increase in the rotational correlation times of the protein-bound agents. These relaxation enhancements are variable, depending upon the site on the protein to which these chelates are bound, and can be as high as approximately 7 mM-1 s-1 at 5 degrees C and approximately 5 mM-1 s-1 at 37 degrees C at 20 MHz (enhancements of approximately 2-5). Change of temperature from 5 to 37 degrees C also appears to switch the relative affinities of these chelates for their primary and secondary binding sites. It is found that the important HSA binding site for the heme breakdown product, bilirubin-IX alpha, is a target for these agents and is the site of highest relaxivity for all the agents.

Bilirubin↗

The effects of the somatostatin analogue, octreotide, on postural hypotension, before and after food ingestion, in primary autonomic failure.

The effects of the somatostatin analogue, octreotide on postural hypotension have been compared with placebo, before and after food ingestion in two groups with primary autonomic failure; patients with pure autonomic failure, and patients with additional neurological involvement as part of multiple system atrophy. After placebo, supine blood pressure was unchanged, but after octreotide, it rose in both groups. Octreotide reduced pre-prandial postural and supine post-prandial hypotension in both pure autonomic failure and multiple system atrophy patients. Postural hypotension post-prandially was considerably worse after placebo; this was reduced after octreotide. Plasma noradrenaline and adrenaline levels remained unchanged. Plasma glucose levels rose higher and faster after placebo. Insulin levels were similar in both groups at rest, but rose higher in patients with pure autonomic failure after placebo. After octreotide, the insulin response in both groups was suppressed. We conclude that octreotide prevents post-prandial hypotension in both groups with primary autonomic failure and additionally reduces postural hypotension both before and after food ingestion. The greater rise in insulin levels in patients with pure autonomic failure suggests that insulin may be a contributing factor to the more severe post-prandial hypotension observed in this group of patients.

Adult↗

Value of non-invasive continuous blood pressure monitoring in the detection of carotid sinus hypersensitivity.

A patient with recurrent episodes of dizziness and blackouts is described. Detailed cardiac and neurological investigations were normal. Autonomic assessment excluded postural hypotension and confirmed normal sympathetic vasoconstrictor function. Cardiac parasympathetic function in response to deep breathing, hyperventilation and ocular pressure was normal. Left carotid sinus massage only reproducibly lowered blood pressure with minimal change in heart rate. This occurred mainly during head-up tilt. The fall in blood pressure was not affected by the muscarinic blocker atropine, or the peptide release inhibitor, octreotide. A diagnosis of left carotid sinus hypersensitivity of the vasodepressor variety was made. Left carotid sinus denervation was performed. This successfully prevented further episodes of dizziness and blackouts. The ability to measure beat-to-beat blood pressure non-invasively was of particular importance in diagnosis, and in the assessment of management options in this patient.

Blood Pressure Determination↗

Modification of the fluorescent allergosorbent test as an inhibition assay for determination of cross-reactivity among aeroallergens.

The fluorescent allergosorbent test was adapted as an inhibition assay to determine cross-reactivity between aeroallergens. With this method, similar antigenic determinants were found between short ragweed and giant ragweed, cocklebur, lamb's-quarter, rough pigweed, marsh elder, and goldenrod. Cocklebur and giant ragweed were highly potent in their ability to competitively bind to short ragweed IgE. The other pollens demonstrated lower potency of cross-reacting antigens. The fluorescent allergosorbent test-inhibition assay appears to be a useful method to determine cross-reactivity among aeroallergens.

Binding, Competitive↗

The influence of food on postural hypotension in three groups with chronic autonomic failure--clinical and therapeutic implications.

The effect of a balanced liquid meal on supine and postural blood pressure (BP) responses was investigated in three groups of patients with chronic autonomic failure; 10 with associated neurological impairment (multiple system atrophy (MSA), Shy-Drager syndrome) and seven without (of which five had pure autonomic failure (PAF); and two had a deficiency of the enzyme dopamine beta hydroxylase, DBH-deficiency). All had marked postural hypotension. Subjects with normal autonomic function were also studied. In MSA and PAF food lowered supine BP substantially, with a more rapid and greater fall in PAF. After food, the levels of BP reached were considerably lower because of the reduced supine BP and many had to be returned to the horizontal position earlier than before. Ingestion of a similar volume of water alone had no effect in MSA or PAF. In DBH deficiency, food had variable but minimal effects on BP while supine and during head-up tilt. In subjects with normal autonomic function food did not affect BP. The BP responses to food thus varied in the three groups with chronic autonomic failure. The influence of food on both supine and postural BP therefore should be considered in the clinical and laboratory assessment of autonomic dysfunction and in relation to therapeutic approaches, designed to alleviate postural hypotension.

Adult↗

cyl encodes a putative cytoplasmic tyrosine kinase lacking the conserved tyrosine autophosphorylation site (Y416src).

We have isolated a cDNA encoding a novel tyrosine kinase family member, named cyl (consensus tyrosine-lacking kinase), from the K562 human leukemia cell line. The deduced cyl protein lacks signal and transmembrane sequences but contains features of known cytoplasmic tyrosine kinases, including amino-terminal SH3 and SH2 domains. However, having very short amino and carboxy termini, cyl does not seem to belong to any of the previously characterized subfamilies of cytoplasmic tyrosine kinases. Furthermore, cyl lacks the highly conserved tyrosine autophosphorylation site (Y416src) in the tyrosine kinase catalytic domain. The cyl gene is located on human chromosome 15. It is expressed ubiquitously as two independently regulated mRNA species of 2.6 and 3.4 kb in human leukemia cell lines and fetal tissues.

Adrenal Glands↗

Brains, bodies and metabolism.

The interrelationship of brain and body sizes has been the subject of investigations for over a hundred years. These studies have demonstrated that variation in brain weights is much smaller than that in body weights; consequently, scaling studies are ones of negative allometry. Furthermore, the variability in brain weight is greater when comparisons are between species rather than among individuals of the same species, and the degree of variability in brain size differs among orders. The largest shifts in brain sizes relative to changes in body weights are found when comparing different ontogenetic stages. Debate continues as to the importance of metabolism in determining the interrelationship of brain-body weights for interpreting differences in relative brain size. Although past advances in the study of brain-body size associations have come by increasing the size of the data bases and by improved statistical analyses, the recent utilization of transgenic animals may provide new insights into the mechanism of this association.

Animals↗

Effect of PO2 and metabolic inhibitors on ionic fluxes across the isolated rabbit corneal endothelium.

Bicarbonate and sodium fluxes were measured across the isolated rabbit corneal endothelium under the influence of several inhibitors. Depression of PO2 in the bathing medium decreased net sodium movement but increased bicarbonate movement. Furosemide did not alter bicarbonate fluxes at either 10(-4) or 10(-5) M, but increased passive sodium flux leading to a decrease in net flux. Thiocyanate, at 5 x 10(-3) or 5 x 10(-2) M, decreased active bicarbonate flux and hence net flux, but had no effect on sodium fluxes. Dinitrophenol increased only the passive bicarbonate flux while decreasing both active and passive sodium fluxes, albeit unequally, leading to a decreased net flux. Ethacrynic acid affected only passive bicarbonate flux, while decreasing net sodium flux. The stilbene derivatives, SITS and DIDS caused opposite effects on both sodium and bicarbonate fluxes. SITS decreased net bicarbonate flux by decreasing active and increasing passive flux, yet increased net sodium flux. DIDS, however, increased net bicarbonate flux but decreased net sodium flux. The results may be explained by current models for endothelial ion transport that include a Na+/H+ antiport and a HCO3-/Na+ symport system in parallel with an independent pathway for HCO3- exit from the endothelial cells. When compared with prior corneal swelling data using these same inhibitors, the maintenance of corneal thickness appears to be dependent on the variation of ion fluxes from normal values, and the dissociation of the two active ion fluxes. In addition, there appears to be a significant ability of ion transport systems to compensate for disturbances to other ion exchange or transport mechanisms.

Animals↗

A comparative review of the primate motor system.

Primates have evolved separately from other mammals since the late Cretaceous, and during this time the two major extant primate groups, prosimians (lorises, lemurs, and tarsiers) and anthropoids (monkeys, apes, and humans) arose. Concurrently, structures within the central nervous system acquired primate characteristics. Not all of the uniquely primate features have been identified in the brain, but several are well known. The pyramidal system, the best studied motor system, shows a distinct primate pattern in its terminal connections in the spinal cord. Other descending systems are less well known, but primate specializations in the vestibular system and red nucleus have been observed. The primary and secondary motor cortices are topographically separated in primates, suggesting one basis for increased complexity. Given the size of the brain, structures in the basal ganglia are relatively enlarged in primates as compared with other mammals, whereas the cerebellum has the same relative size.

Journal Article↗

Gyrification in the cerebral cortex of primates.

The degree of cortical folding in primates has been analyzed using a gyrification index (GI). Correlation analyses of the GI with body weight, brain weight and neopallial volume show that the human data fit the general trend of the nonhuman anthropoids. Bigger primate brains exhibit a higher degree of fissurization, but a taxonomic difference that is independent of brain weight between prosimians and anthropoids has also been observed. In these regressions, anthropoids differed from prosimians by having a larger increase in gyrification for every unit increase in body or brain weight or neopallial volume. A stepwise regression also shows a prosimian-anthropoid difference. The best predictor for convolutedness in anthropoids is neocortical volume, while in prosimians it is brain weight. The GI in catarrhines is correlated with total sulcal length but not number of sulci. This result suggests paleontological studies of total sulcal length can give direct information on the evolution of cortical folding in primates.

Animals↗

The human pattern of gyrification in the cerebral cortex.

The degree of cortical folding found in adult human brains has been analyzed using a gyrification index (GI). This parameter permits the description of a mean value for the whole brain, but also a local specific analysis of different brain regions. Correlation analyses of the GI with age, body weight, body length, brain weight and volume of the prosencephalon and the cortex show no significant results. GI values do not differ significantly between male and female brains, right and left hemispheres or right and left sides of the superior temporal plane. The GI shows maximal values over the prefrontal and the parieto-temporo-occipital association cortex. A comparison between the rostro-caudal GI patterns of human brains and those of prosimians and Old World monkeys shows the largest difference over the prefrontal cortex. The mean GI increases from prosimians to human brains with the highest values for non-human primates being in the pongid group.

Adolescent↗

Serum concentrations of trypsin-like immunoreactivity and pancreatic isoamylase in insulin dependent diabetic patients.

Serum trypsin-like immunoreactivity and pancreatic isoamylase were measured in 302 insulin-dependent diabetic patients (166 men) using radioimmunoassay for the former and a photocolorimetric method for the latter. There was a significant correlation between the two enzymes (r = 0.67, p less than 0.0001) with lower concentrations of both trypsin-like immunoreactivity (208.8 micrograms/L) and pancreatic isoamylase (67.5 U/L) in diabetic patients as compared to controls (p less than 0.0001). Using multiple regression analysis, a statistically significant association was only apparent between enzyme concentrations and age at onset of diabetes (r = 0.31, p less than 0.0001). The results suggest that impaired exocrine pancreatic function may occur in an appreciable proportion of diabetic patients and also that a primary insult to the exocrine pancreas occurring at the time of endocrine injury may be a contributory factor.

Adolescent↗

Femoral expansion in the adult male rat.

The length, total and cortical widths at midshaft, and robusticity of femora were measured in growing and mature male Holtzman rats. Analysis of covariance revealed significant differences in the regression coefficients (slopes) between young rats (1-4 months) and adult rats (5-16 months), indicating that, for a given increment in femoral length, young rats have a smaller increment in total femoral width than do adult rats. In addition, the results indicated that femoral expansion occurs in adult male Holtzman rats (5-16 months of age) without cortical thinning or loss of bone mass.

Age Factors↗

Relative size of the anterior thalamic nuclei differentiates anthropoids by social system.

Anthropoid primates differ in the sizes of their limbic nuclei. Morphometric analysis of the anterior principal thalamic nucleus and the medial mamillary nuclei reveal that both regions increase in size as a function of brain weight. However, after controlling for the size of the brain, anthropoids classified as having single-male societies have more anterior principal thalamic neurons than do primates that are classified as multi-male. The relative sizes of the mamillary nuclei do not show this clustering. The differences in the size of the anterior nucleus are hypothesized to be specific for this nucleus and not the result of a general limbic or of heterochronic changes.

Animals↗

Quantitative cytoarchitectonics of the posterior cingulate cortex in primates.

The cytoarchitecture of four cortical areas within the posterior cingulate region and the differences among them are quantitatively analyzed in 17 primate species. The transition from allocortex (area 29) to isocortex (areas 30, 23, and 31) is characterized by shifts in laminar proportions and cellular densities. The molecular layer and inner main lamina (layers V and VI) occupy a smaller proportion of the cortex in iso- than in allocortex, while conversely, the outer main lamina (layers II and III) makes up a larger proportion of the cortex in iso- than in allocortex. Layer IV is relatively larger in area 31 than in area 23. The packing densities of cell bodies were determined by gray-level index values. These values show that the isocortex has lower cell densities in the outer main lamina, but higher cell densities in the inner main layers. Furthermore, the granular layer of area 31 is more densely packed than it is in area 23. These results are discussed as structural correlates of a relative increase in the receptive and processing capacities of the isocortex over the adjacent allocortex.

Animals↗

Comparative aspects of the primate posterior cingulate cortex.

Cytoarchitecturally defined cortical areas of the posterior cingulate gyrus differ morphometrically among the major taxonomic divisions of primates. Prosimians and anthropoids have different laminar proportions in the isocortical regions (areas 30, 23, and 31); anthropoids have relatively larger outer main laminae and granular layers than prosimians. In the granular retrosplenial cortex (area 29), however, prosimians and anthropoids differ only in the proportion of the molecular layer to the rest of the cortex. On the other hand, the proportions of the inner and outer main laminae of area 29 differ between the infraorder divisions of Anthropoidea, the catarrhines, and the platyrrhines. The platyrrhines (New World monkeys) have apparently specialized by increasing the outer main lamina of area 29, which contains afferent and intracortical connections. Among all primates, the amount of neuropil in each cortical region changes as a function of brain weight, but within each area, the neuropil maintains a constant ratio between the outer and inner laminae. These observations suggest that neuropil ratios are conservative features in primates and that evolutionary changes more frequently involve shifts in volumetric proportions. Furthermore, the platyrrhine-catarrhine differences in area 29 likely evolved after the prosimian-anthropoid differences were established in the isocortical cingulate regions.

Animals↗

Enlarged limbic structures in the human brain: the anterior thalamus and medial mamillary body.

Major paradigms about human evolution stress the increase of cognitive capabilities, while considering our emotional and limbic systems to be relatively unchanged. Morphometric analyses of two limbic structures, the anterior thalamic nuclei (AP) and the medial mamillary bodies (MB), in 27 primate species show, however, that: human nuclei are as large as MB or larger AP than differences in anthropoid brain sizes predict; and prosimians and anthropoid patterns differ.

Animals↗

A new Golgi method for adult human brains.

A new fast and reliable Golgi method to impregnate neurons in adult human brains which have been routinely fixed in neutral buffered formalin is described. In addition to potassium dichromate and sucrose, this technique uses microwave energy and hydrogen peroxide. Dendrites and perikarya of cortical pyramidal neurons and large subcortical multipolar neurons are the neuronal structures most commonly impregnated by this method.

Animals↗