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Biomedical subjects

D L Armstrong

Publications and source records attributed to D L Armstrong.

At least 73 records · Page 4Linked to original sources
PubMed1994

Fatal group A streptococcal meningitis and toxic shock-like syndrome: case report.

A previously healthy 8-year-old girl presented with flu-like symptoms, developed toxic shock-like syndrome, and died within 48 hours. At autopsy she was found to have purulent meningitis. The group A beta-hemolytic streptococcus isolated from her CSF was a member of clone ET 2. This strain produced a variant form of streptococcal pyrogenic exotoxin A (SPEA 2) that has recently been associated with widespread toxic shock-like syndrome.

Brain↗
PubMed1994

Glial cell nuclear hypertrophy in complex partial seizures.

The white matter of resected temporal lobes from patients with intractable complex partial seizures shows increased cellularity which appears to be related to glia and neurons. This study, using quantitative methods, defines an increase in glial cell numbers and a significant increase in glial nuclear size within a defined area of white matter in the lateral temporal lobe. Evaluation was made on specimens from ten patients with complex partial seizures compared with two patients with non-epileptic brain lesions and five autopsy patients with no neurologic disease. The importance of recognizing these alterations in glia and the possible relevance to the pathoetiology of epilepsy are discussed.

Adolescent↗
PubMed1994

Seasonal effects on seminal and endocrine traits in the captive snow leopard (Panthera uncia).

The annual reproductive cycle of the male snow leopard (Panthera uncia) was characterized by evaluating seminal and endocrine traits monthly. Testicular volume was greatest (P < 0.05) during the winter months when the quality of ejaculate was optimal. Ejaculate volume, total sperm concentration ml-1, motile sperm concentration per ejaculate, sperm morphology and sperm motility index were lowest during the summer and autumn months compared with the winter and spring. Peripheral LH, FSH and testosterone concentrations were also lowest during the summer months, increasing during the autumn just before the increase in semen quality, and were maximal during the winter months. There was a direct relationship (P < 0.01) between: (1) testosterone and testicular volume, total sperm concentration ml-1, motile sperm concentration per ejaculate and ejaculate volume, and (2) LH and testicular volume and motile sperm concentration per ejaculate. In summary, although spermatozoa were recovered throughout the year, optimal gamete quality was observed during the winter and spring. Although previous studies in felids have demonstrated seasonal effects on either seminal or endocrine traits, this is the first study to demonstrate a distinct effect of season on both pituitary and testicular function.

Animals↗
PubMed1994

Angiotensin AII AT1 receptor mediates ethanol-diazepam inhibition of hippocampal LTP.

Within a limited range of doses, co-administration of ethanol (EtOH) and diazepam (DZ) produce enhanced anxiolytic effects. These combined effects on long-term potentiation (LTP) in the hippocampus of rats anesthetized with urethane were studied in an attempt to provide an explanation at a more fundamental neuronal level. Male Sprague-Dawley rats received 0.1, 0.5, 0.75 and 1.0 mg/kg DZ i.p. in combination with 0.1, 0.5, 0.75 g and 1.0 g/kg EtOH by gavage, respectively. Drugs were administered 20 min (EtOH) and 15 min (DZ) prior to tetanic stimulation of the medial perforant path which resulted in LTP induction measured in terms of the relative change in amplitude of the population EPSP as compared to baseline. Effects of both drugs alone and in combination on LTP are presented. Both drugs depressed LTP induction and significant enhanced interactive effects were observed. We have previously shown that angiotensin II (AII) inhibits LTP induction and that the inhibition can be blocked by losartan, an AII AT1 receptor antagonist. Our present results demonstrate that the combined inhibitory effects of EtOH and DZ on LTP induction are also blocked by losartan.

Angiotensin II↗
PubMed1993

Pathologic characterization of short-chain acyl-CoA dehydrogenase deficiency in BALB/cByJ mice.

BALB/cByJ mice have a deficiency of short-chain acyl-CoA dehydrogenase (SCAD) and are a useful model for studying the inborn errors of fatty acid metabolism which affect humans. Patients with some of these disorders present with hypoglycemia, hyperammonemia, and microvesicular fatty change of hepatocytes. In the present study we examined pathogen-free, SCAD deficient BALB/cByJ mice and control BALB/cBy mice for biochemical and tissue changes following fasting or salicylate challenge. We observed mitochondrial swelling and microvesicular fatty changes in hepatocytes in mutant mice, especially severe following a fast. However, fasting did not alter their blood ammonia and there was no apparent clinical disease. Similarly, salicylates did not produce disease in the BALB/cByJ mice. We did detect in mice an alternative pathway for salicylate metabolism, by-passing glycine conjugation which is the principal metabolic pathway in humans.

Acyl-CoA Dehydrogenase↗
PubMed1993

Chronic exposure to environmental levels of lead impairs in vivo induction of long-term potentiation in rat hippocampal dentate.

This study examined the effects of chronic developmental lead (Pb) exposure in rats on hippocampal long-term potentiation (LTP). Male offspring were exposed to 0.2% Pb acetate continuously from birth until testing at 85-105 days. Excitatory postsynaptic potential (EPSP) and population spike amplitudes were measured in the dentate hilar region in response to stimulation applied to the lateral perforant path. LTP was induced in control animals with an average maximal EPSP potentiation of 41%, which was significantly greater than the increase in EPSP amplitudes (2%) in exposed animals after tetanizing stimulation. Current-voltage curves in controls demonstrated significant increases in EPSPs and population spikes after application of pulse trains to induce LTP, while exposed rats exhibited no discernible change in responses. These findings suggest that induction or development of LTP in the dentate hilar region in vivo is impaired by chronic developmental exposure to environmentally relevant levels of Pb.

Animals↗
PubMed1993

Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation.

Natriuretic peptides inhibit the release and action of many hormones through cyclic guanosine monophosphate (cGMP), but the mechanism of cGMP action is unclear. In frog ventricular muscle and guinea-pig hippocampal neurons, cGMP inhibits voltage-activated Ca2+ currents by stimulating phosphodiesterase activity and reducing intracellular cyclic AMP; however, this mechanism is not involved in the action of cGMP on other channels or on Ca2+ channels in other cells. Natriuretic peptide receptors in the rat pituitary also stimulate guanylyl cyclase activity but inhibit secretion by increasing membrane conductance to potassium. In an electrophysiological study on rat pituitary tumour cells, we identified the large-conductance, calcium- and voltage-activated potassium channels (BK) as the primary target of another inhibitory neuropeptide, somatostatin. Here we report that atrial natriuretic peptide also stimulates BK channel activity in GH4C1 cells through protein dephosphorylation. Unlike somatostatin, however, the effect of atrial natriuretic peptide on BK channel activity is preceded by a rapid and potent stimulation of cGMP production and requires cGMP-dependent protein kinase activity. Protein phosphatase activation by cGMP-dependent kinase could explain the inhibitory effects of natriuretic peptides on electrical excitability and the antagonism of cGMP and cAMP in many systems.

Animals↗
PubMed1993

Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings.

We report three siblings born with severe neonatal encephalopathy, manifested clinically by microcephaly, myoclonus, and muscular hypertonus. Karyotypic analyses and all biochemical investigations were unrevealing. All three patients died during infancy. Postmortem examination of the brain in one child disclosed severe neuronal loss in the inferior olives and the pontine nuclei. There was also severe hypoplasia of the cerebellum and micrencephaly. There was diffuse gliosis of the white matter in all areas of the brain. We believe this may represent a previously undescribed form of familial infantile encephalopathy with olivopontocerebellar hypoplasia.

Brain↗
PubMed1993

Role of angiotensin II and AT1 receptors in hippocampal LTP.

Results of a previous study showed that angiotensin II (AII) inhibited the induction of long-term potentiation (LTP) in hippocampal granule cells in response to dorsomedial perforant path stimulation in urethane-anesthetized rats. The results of present experiments demonstrate a dose-dependent inhibition of LTP induction under the same conditions due to ethanol (EtOH) administered by stomach tube and diazepam (DZ) injected IP. The inhibition of LTP induction by EtOH and DZ can be blocked by saralasin (SAR) applied directly to the dorsal hippocampus and by lorsartan (DuP 753) administered IP. Lorsartan or a metabolite crosses the blood-brain barrier because it also blocks the inhibition of LTP induction due to AII administration directly into the dorsal hippocampus. Lorsartan is a competitive antagonist of the AT1 subtype AII receptor. Therefore, the AII and the EtOH and DZ inhibition of LTP induction are mediated by the AII subtype receptor AT1. AIII and the AT2 antagonist PD123319 did not produce any significant effects. These in vivo effects can be reproduced in brain slices and therefore cannot be attributed to other factors, such as the urethane. In addition, electrical stimulation of the lateral hypothalamus (LH) inhibits LTP induction, and the inhibition can be blocked by SAR. These data on LH stimulation indicate that LH AII-containing neurons send axons into the hippocampus that inhibit the induction of LTP. These results not only provide new information on a neurotransmitter involved in the amnesic effects of benzodiazepines and ethanol-induced memory blackouts, but also testable hypotheses concerning recent observations that angiotensin converting enzyme (ACE) inhibitors elevate mood and improve certain cognitive processes in the elderly.

Angiotensin II↗
PubMed1993

Peroxisomal disorders in children: immunohistochemistry and neuropathology.

Immunohistochemical studies with antisera against four peroxisomal enzymes, catalase and beta-oxidation enzymes (acyl-coenzyme A oxidase, bifunctional protein, and 3-ketoacyl-CoA thiolase), were performed on brain, liver, and kidney specimens from patients with peroxisomal disorders, as well as specimens from three control subjects, by using conventional paraffin-embedded autopsy material. The patients included eight with Zellweger syndrome and one with neonatal adrenoleukodystrophy. In the liver and kidney specimens from all patients, except one with Zellweger syndrome, diffuse immunostaining with all antisera in the cytoplasm of hepatocytes and renal tubular epithelium suggested an absence of peroxisomes but the presence of peroxisomal enzymes. Examination of brain specimens indicated a weak or negative reaction of neurons in the cerebral cortex and a weak reaction of glial cells in the white matter, which suggested maturational delay compared with control subjects. The delayed immunoreactive pattern of peroxisomal enzymes in Zellweger syndrome and neonatal adrenoleukodystrophy may be related to the significant neuropathologic features of polymicrogyria and dysmyelinogenesis. One patient with Zellweger syndrome had a unique finding of a positive granular catalase reaction and a negative reaction with antisera to 3-ketoacyl-coenzyme A thiolase, which suggested a diagnosis of pseudo-Zellweger syndrome. This study validates the application of these immunohistochemical methods to the study of peroxisomal enzymes. Use of these methods improves the accuracy of diagnosis of peroxisomal disorders.

Acetyl-CoA C-Acyltransferase↗
PubMed1993

Preterm periventricular axonal and myelin injury.

Injury to the periventricular axons and myelin in the preterm infant occur at a vulnerable period of brain development and may be associated with devastating brain lesions and neurological sequelae. Ultrasonography in the newborn period identifies the site and extent of lesions and is useful in predicting the outcome for surviving infants. The etiology of the most common lesion, PVL, is incompletely understood and will require continuing studies so that causes may be eliminated and appropriate therapies instigated.

Axons↗
PubMed1992

An enzymatic mechanism for potassium channel stimulation through pertussis-toxin-sensitive G proteins.

Many neurotransmitters inhibit secretion from electrically excitable cells by activating pertussis-toxin-sensitive G proteins that modulate voltage-gated ion channels. Recent electrophysiological studies of metabolically intact cells from mammalian and molluscan neuroendocrine systems have implicated protein phosphatases in this process. In this article David Armstrong and Richard White review these studies and suggest a biochemical pathway that might link one of the G proteins to protein phosphatase activity.

Animals↗
PubMed1992

Ability of thawed tiger (Panthera tigris) spermatozoa to fertilize conspecific eggs and bind and penetrate domestic cat eggs in vitro.

Electroejaculates from tigers were collected and half was used fresh to inseminate tiger eggs in vitro and domestic cat eggs stored in a hypertonic salt solution. The remainder was pelleted, frozen in a solution of 20% egg yolk, 11% lactose and 4% glycerol, thawed and cultured with tiger and domestic cat eggs. The motility index ((sperm % motility)+(status rating x 20))/2 for thawed spermatozoa was about 86% of that in fresh aliquots. Of the 49 tiger oocytes inseminated in vitro with fresh spermatozoa, 34 (69.4%) cleaved, compared with 33 of 47 oocytes (70.2%) cultured with thawed spermatozoa (P > 0.05). Embryos generated by either sperm treatment could develop in vitro to the 16-cell or morula stage. Fresh and thawed tiger spermatozoa were equally capable (P > 0.05) of binding and penetrating the outer and inner zona pellucida of domestic cat eggs. These results demonstrate the ability of frozen-thawed tiger spermatozoa to (i) penetrate homologous and heterologous eggs and (ii) result in conspecific, advanced development of preimplantation embryos in vitro.

Animals↗
PubMed1992

Trimethyltin alters membrane properties of CA1 hippocampal neurons.

Trimethyltin produces pathological changes in the hippocampus, but the physiological mechanisms underlying its toxicity remain unclear. Intracellular recordings of CA1 neurons in rat hippocampal slices were conducted during bath application of 50 and 100 microM trimethyltin and 50 and 200 microM dimethyltin. Trimethyltin slowly depolarized the membrane potential without spontaneous spiking, and decreased input resistance and time constant. Trimethyltin decreased, in a dose-dependent manner, both the elicited action potential and the orthodromically-stimulated action potential amplitudes; increased the threshold current for both elicited and orthodromically-stimulated action potentials; and prolonged the duration of the orthodromic excitatory post-synaptic potential. These trimethyltin-induced effects were not readily reversed. On the other hand, dimethyltin at high concentrations only reduced the amplitude of the orthodromic action potential. Slice viability was compromised following exposure to trimethyltin, but not following dimethyltin. These data demonstrate that decreased membrane time constant and input resistance is an early and reliable indicator of the onset of trimethyltin-induced changes. The effects do not resemble those produced by excitotoxins, but rather share similarities with responses observed during slice hypoxia.

Action Potentials↗
PubMed1991

Angiotensin II blocks hippocampal long-term potentiation.

We have found that injection of angiotensin II (AII) above the hippocampus in the intact rat blocks the induction of long-term potentiation (LTP) in perforant path-stimulated dentate granule cells. A minimum dose of 4.78 pmol AII was required for the complete blockade of LTP and this blockade was entirely prevented if the AII-specific antagonist saralasin was co-injected at a 50-fold molar excess. AII thus appears to act via AII receptors and does not cause non-specific inhibition. The injection of saralasin alone yielded LTP comparable to that obtained when vehicle was injected. Angiotensin III was found to be 40-50 fold less potent than AII in blocking LTP. Both AII and AII receptors of unknown function occur in the hippocampal formation. The results reported here suggest a role for these molecules in the control of hippocampal LTP.

Amino Acid Sequence↗
PubMed1991

Activation of Ca2+ entry into acinar cells by a non-phosphorylatable inositol trisphosphate.

In many cell types, receptor activation of phosphoinositidase C results in an initial release of intracellular Ca2+ stores followed by sustained Ca2+ entry across the plasma membrane. Inositol 1,4,5-trisphosphate is the mediator of the initial Ca2+ release, although its role in the mechanism underlying Ca2+ entry remains controversial. We have now used two techniques to introduce inositol phosphates into mouse lacrimal acinar cells and measure their effects on Ca2+ entry: microinjection into cells loaded with Fura-2, a fluorescent dye which allows the measurement of intracellular free calcium concentration by microspectrofluorimetry, and perfusion of patch clamp pipettes in the whole-cell configuration while monitoring the activity of Ca(2+)-activated K+ channels as an indicator of intracellular Ca2+. We report here that inositol 1,4,5-trisphosphate serves as a signal that is both necessary and sufficient for receptor activation of Ca2+ entry across the plasma membrane in these cells.

Animals↗
PubMed1991

Somatostatin stimulates Ca(2+)-activated K+ channels through protein dephosphorylation.

The neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain. In mammalian pituitary tumour cells somatostatin inhibits secretion through two distinct pertussis toxin-sensitive mechanisms. One involves inhibition of adenylyl cyclase, the other an unidentified cyclic AMP-independent mechanism that reduces Ca2+ influx by increasing membrane conductance to potassium. Here we demonstrate that the predominant electrophysiological effect of somatostatin on metabolically intact pituitary tumour cells is a large, sustained increase in the activity of the large-conductance Ca(2+)- and voltage-activated K+ channels (BK). This action of somatostatin does not involve direct effects of Ca2+, cAMP or G proteins on the channels. Our results indicate instead that somatostatin stimulates BK channel activity through protein dephosphorylation.

Animals↗