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Biomedical subjects

L M Robertson

Publications and source records attributed to L M Robertson.

31 records · Page 2Linked to original sources
PubMed1993

Characterization of the UL10 gene product of herpes simplex virus type 1 and investigation of its role in vivo.

On the basis of predicted amino acid sequence characteristics, herpes simplex virus type 1 gene UL10 is thought likely to encode a membrane protein with eight potential transmembrane regions. Previously, a protein with an apparent M(r) 47,000 on SDS-PAGE was identified as a product of this gene. Here we have further characterized this protein, and show that it is modified by N-linked glycosylation, associates with membranes from infected cells, and is a component of the virus particle. It is not essential for virus growth in tissue culture. To investigate its role in vivo a deletion mutant lacking the majority of the UL10 open reading frame was constructed (UL10-del). The in vitro growth properties of this virus were consistent with previous studies; it grew to give slightly lower yields than wild-type and revertant viruses, and had no apparent temperature-sensitive or host range phenotype. In vivo, in a mouse model, UL10-del was capable of establishing a latent infection, although it was impaired for growth at the periphery, and for spread to and/or growth within the nervous system relative to wild-type or revertant viruses.

Animals↗
PubMed1993

Biomaterials in medicine--a bioengineering perspective.

Biomaterials are considered with an emphasis on those used in artificial organs. Attention is drawn to the importance of the polymeric biomaterials and factors which affect their properties. Functions of membranes, sorbents, blood tubing, ventricular diaphragms and cell culture substrates are examined in order to obtain a summary of fundamental properties. Observations are made on the importance of blood compatibility assessment and its association with a biomaterial structure-property relationship. Blood-biomaterial interactions are discussed in terms of an overall relationship between the three components--blood, biomaterial and antithrombotic agent, with examples given of factors influencing each component. Cell-biomaterial interactions are examined in the areas of toxicity evaluation and the promotion of cell attachment and growth, where an overall relationship is described for the cell, growth medium and growth factors, and the biomaterial acting as a substrate.

Animals↗
PubMed1992

Peripheral replication and latency reactivation kinetics of the non-neurovirulent herpes simplex virus type 1 variant 1716.

The terminal portion of the herpes simplex virus (HSV) genome long repeat region has been shown to contain a neurovirulence gene. Both HSV-1 and HSV-2 mutants deleted in this gene fail to cause central nervous system (CNS) disease in mice. The HSV-1 strain 17 variant 1716, which has a 759 bp deletion encompassing the gene, grows normally in tissue culture but fails to grow following intracerebral inoculation of mice. This paper demonstrates that 1716 is capable of peripheral replication in the footpads of mice. However, no acute replication of virus is detectable in dorsal root ganglia up to 10 days after footpad inoculation. These results imply that the replication defect in 1716 is not host-specific, but is tissue- and/or cell type-specific. Latency reactivation kinetics demonstrate that 1716 is capable of establishing a latent infection, but the kinetics of reactivation are significantly impaired compared to wild-type virus and are dose-dependent. Lack of acute ganglionic replication combined with impaired reactivation kinetics support the conclusion that a proportion of 1716 genomes initiate a lytic infection which then aborts, and a proportion enter the latent state. The results with 1716 imply that its inability to replicate in CNS and peripheral nervous system neurons is specific, and that the block in replication is beyond the stage of adsorption and entry. A prerequisite for any live attenuated HSV vaccine is an inability to initiate CNS involvement following peripheral inoculation. In this respect, 1716 has prototype vaccine potential with the proviso that a direct extrapolation is being made from mouse to man.

Animals↗
PubMed1989

Seizure disorders and trauma.

The prevalence of seizure disorder diagnosis in the general population is between 0.5% and 2.0%. Seizures may be manifested by abnormal motor activity, loss of muscle tone, and changes in mental status. Seizure may increase an individual's risk for traumatic injury by adversely influencing performance in a particular situation. We identified 30 patients admitted to our trauma service over a three-year period with injury related to seizure; 16 were male and 14 were female, with a mean age of 34.8 years. Twenty-eight patients (93%) had a history of seizure activity, with the mean duration of seizure activity of 16.5 years (range, three to 40 years). Both seizure diagnosis and etiology were multifactorial. Multiple drug therapy predominated, phenytoin (Dilantin) being the most frequently used medication. Overall compliance was poor (53%). Only blunt injury occurred in these patients, 50% suffering injury from falls. Injuries from motor vehicle accidents (40%) were the next most frequent (auto crash in seven cases, motorcycle crash in four, and bicycle crash in one case). The remainder of the injuries were burns (10%). Nine patients (30%) required operation. Skeletal injuries predominated (67%). Patients with a history of seizure will be frequently encountered by physicians of all specialties. The patients likely to be at increased risk for injury are noncompliant, have breakthrough seizures (ie, despite therapy), or have the metabolism of their seizure medication altered by alcohol or other drugs. To prevent potentially serious injury, these patients should be identified and counseled.

Accidental Falls↗
PubMed1989

Influence of plasticised poly(vinyl chloride) on platelet adhesion and platelet aggregates.

The most widely used plasticiser for poly(vinyl chloride) (PVC) is di-(2-ethyl-hexyl) phthalate (DEHP), which is extracted in contact with blood. One approach to reducing plasticiser extraction is to incorporate the higher molecular weight plasticisers trioctyl trimellitate (TOTM) and polymeric adipate (PA). This investigation has compared the influence of these plasticisers with that of DEHP on platelet adhesion and platelet aggregate formation. PVC tubing was tested in the absence of anticoagulants and in the presence of heparin. Our results demonstrate the influence of plasticisers on platelet response and support the view that evaluation of such plasticisers should be extended from an examination of toxicological properties to a comprehensive blood compatibility assessment.

Adipates↗
PubMed1988

Circadian clock in cell culture: I. Oscillation of melatonin release from dissociated chick pineal cells in flow-through microcarrier culture.

The avian pineal gland contains circadian oscillators that regulate the rhythmic release of melatonin. We have developed a dissociated chick pineal cell culture system in order to begin a cellular analysis of this vertebrate circadian oscillator. Dissociated pineal cells maintained in cyclic light conditions (LD 12:12) released melatonin rhythmically. The release of melatonin was elevated during the dark and low during the light. A circadian oscillation of melatonin release persisted for at least 5 cycles in constant darkness with a period close to 24 hr; however, there was a gradual damping of the amplitude. Analysis of the rhythm revealed that the observed damping was consistent with either desynchronization of multiple oscillators within the cultures or damping of individual oscillators. The circadian oscillation of melatonin release persisted for up to 4 cycles under conditions of constant light; however, the oscillation was strongly damped and the period of the oscillation was lengthened significantly. Thus, dissociated pineal cells express a persistent circadian oscillation of melatonin release in constant darkness, and properties of this oscillation are modulated by light treatment in vitro. This flow-through cell culture method for dissociated chick pineal cells should provide a useful model for the analysis of a vertebrate circadian system at the cellular level.

Animals↗
PubMed1988

Circadian clock in cell culture: II. In vitro photic entrainment of melatonin oscillation from dissociated chick pineal cells.

The avian pineal gland contains circadian oscillators that regulate the rhythmic synthesis of melatonin. We have developed a flow-through cell culture system in order to begin to study the cellular and molecular basis of this vertebrate circadian oscillator. Pineal cell cultures express a circadian oscillation of melatonin release for at least 5 cycles in constant darkness with a period close to 24 hr. In all circadian systems, light regulates the rhythm by the process of entrainment that involves control of the phase and period of the circadian oscillator. In chick pineal cell cultures we have investigated the entraining effects of light in 2 ways: by shifting the light-dark cycle in vitro and by measuring the phase-shifting effects of single light pulses. A 6 hr advance or delay of a LD 12:12 light-dark cycle produced a corresponding shift in the melatonin rhythm. The phase shifts of the rhythms persisted after transfer to constant darkness, showing that the underlying circadian oscillator was entrained. Photic entrainment of the oscillator was further characterized by measuring the phase-shifting effects of single 6 hr light pulses. Single pulses of light shifted the phase of the circadian oscillator in a phase-dependent manner. Light pulses beginning early in the subjective night delayed the phase of the oscillation 8 hr relative to dark controls. Conversely, light pulses beginning late in the subjective night advanced the phase of the oscillation nearly 8 hr. Thus, photoreceptors within the cell cultures can mediate entrainment of the pineal oscillators.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Ethanol-stimulated endorphin and corticotropin secretion in vitro.

Although acute administration of ethanol in vivo results in increased plasma glucocorticoid concentration, it is unclear whether this effect is mediated by corticotropin (ACTH) from the anterior pituitary. Secretion of beta-endorphin-like (BE-IR) and corticotropin-like (ACTH-IR) immunoreactivity from perifused, dispersed mouse adenohypophyseal cells was used to evaluate the effect of 17 mM ethanol on secretion of pituitary peptides. Cells were also exposed to 10 nM synthetic corticotropin-releasing factor (CRF), 1 microM vasopressin, 54 mM KCl, 100 nM corticosterone, and calcium-free medium, separately and in combination. Secretion of BE-IR and ACTH-IR were markedly sensitive to low concentrations of ethanol. Exposure to 17 mM ethanol produced 3-fold stimulation of the rate of hormone release. This represented one-third to two-thirds that of the rate of maximum stimulation by CRF. Unlike CRF-stimulated secretion, ethanol-stimulated secretion was transient. Further, a second ethanol exposure 1 h after the first did not stimulate peptide secretion. Similar to CRF-stimulation, ethanol-stimulated peptide secretion required extracellular calcium and was inhibited by the glucocorticoid corticosterone. We suggest that this system is a useful model for investigation of the actions of low concentrations of ethanol at the cellular level.

Adrenocorticotropic Hormone↗
PubMed1984

Potassium modulation of corticosterone secretion from perifused mouse adrenal cells.

Potassium has long been recognized as a significant modulator of aldosterone synthesis and secretion. Its role as a regulator of glucocorticoids is less clear. Using a perifusion of dispersed mouse adrenal cells, we found a dose-related effect of extracellular potassium (K+) on secretion of the major rodent glucocorticoid, corticosterone. The maximal elicitable responses was 33% of the maximal response to ACTH. An increase in K+ concentration enhanced the effect of ACTH, while K+-free medium depressed the response to ACTH. The temporal characteristics of the corticosterone response to K+ were similar to that of ACTH and consistent with a primary effect on biosynthesis rather than on discharge of a preformed pool of hormone. The results indicate that a significant ion-mediated mechanism modulates ACTH-stimulated glucocorticoid secretion and suggest that further studies of endogenous substances operative by ionic mechanisms might be warranted.

Adrenal Glands↗
PubMed1983

Ethanol dependence and the pituitary adrenal axis in mice. II. Temporal analysis of dependence and withdrawal.

The effects of ethanol dependence and withdrawal on pituitary hormone content and corticosterone release were investigated in AKR/J male mice in a vapor chamber. Both chronic ethanol inhalation and ethanol withdrawal were associated with increased adenohypophyseal-adrenocortical activity. Operationally, ethanol exposure was a stressor. Both physical dependence and withdrawal led to increased secretion/synthesis ratios of peptide hormones. The temporal pattern of pituitary ACTH-IR content changes was different from that of beta-endorphin-IR and alpha-MSH-IR. Differences in the pattern of ACTH-IR and alpha-MSH-IR most probably represent lobe-specific differences in the response to chronic ethanol exposure and withdrawal.

Adrenal Glands↗
PubMed1983

Potassium-modulated secretion of immunoreactive melanocyte-stimulating hormone and endorphin from mouse neuro-intermediate lobes: evidence for stimulus-secretion uncoupling and rate sensitivity.

UNLABELLED: A multi-chamber perifusion system, capable of detecting transient secretory events, was used to define the roles of stepwise changes and gradients of K+ concentration in modulation of alpha-MSH and endorphin secretion. Fifteen dispersed mouse neuro-intermediate lobes per chamber were perifused with Dulbecco's Modified Eagle Medium at 0.5 ml/min. One-min fractions were collected. Ten min of 67 mM K+ elicited an immediate, very brief 4-fold increase in secretion of both hormones. Surprisingly, the return to normal K+ elicited a similar increase in secretion. Ten min K+-free medium produced an immediate decrease in secretion. Exposure to a 10-min 0-67 mM K+ gradient did not produce an increase in secretion; however, the stepwise return to normal K+, identical to that in the first experiment, elicited an immediate, brief increase in secretion. CONCLUSIONS: 1) The rapid decline in secretory activity during 67 mM K+ cannot be explained either by "down regulation" of receptors, since this secretagogue is not receptor-mediated, or by depletion of labile hormone, since a second secretory episode occurred immediately following termination of high K+. This suggests that some other cellular mechanism "uncouples" stimulus-secretory mechanisms. 2) Although depolarization with high K+ and hyperpolarization with K+-free medium were associated with increases and decreases, respectively, in secretion, it appears that it is the rate of ion flux rather than polarization which is responsible for stimulus-secretion coupling.

Animals↗