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D A Gordon

Publications and source records attributed to D A Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1992

Regulation of expression of the reovirus receptor on differentiated HL60 cells.

The reovirus receptor on mammalian cells has not been fully characterized and controversy exists over the nature of this receptor. We report here that the expression of this receptor is dependent on the differentiation status of a human promyelocytic leukaemia cell line (HL60). Phorbol treatment of HL60 cells for 24 h, at a concentration range of 160 nM down to 1 nM, led to differentiation of these cells towards monocytes and a loss of approximately 80% of their ability to bind reovirus in a fluorescence assay. These cells also lost their susceptibility to T1 and T3 reovirus infection. DMSO treatment for 24 h at a concentration of 1.25% (v/v) led to differentiation towards granulocytes. This was accompanied by an increase of approximately 15% in binding of reovirus to these cells. After being infected by T1 or T3 reovirus, the granulocytes produced higher titres of progeny virus than did untreated HL60 cells. Similar differences were noted when virus binding to HL60 cells was assayed using radiolabelled reovirus. These effects were not detected when murine L fibroblasts were treated with DMSO or phorbol. ATCC-derived murine R1.1 cells did not bind reovirus. Competition data indicated that there may be two reovirus receptors on HL60 cells, and that T1 can bind to only one receptor whereas T3 can bind to both receptors. Our data also suggested that the beta-adrenergic receptor was unlikely to act as the reovirus receptor on HL60 cells.

Animals↗
PubMed1990

Motor-unit force potentiation in adult cats during a standard fatigue test.

1. The purpose of this study was to examine the time course of tetanic force during a standard fatigue test and to distinguish between the appearance of potentiation and fatigue among the four motor-unit types of a cat hindlimb muscle. 2. Motor units of the tibialis posterior muscle in the adult cat were assigned to four categories (i.e. types S, FR, FI, FF) based on conventional criteria (Burke, Levine, Tsairis & Zajac, 1973). The mean (+/- S.D.) time course of peak force was constructed for each motor-unit type and, within each type, for those units that potentiated (a greater than 3% increase in peak force compared to the initial value) and those that did not potentiate. 3. The average time courses of force differed between motor-unit types. There was, however, considerable variability within each motor-unit type. For the same relative force output, the forces exerted by slow-twitch units were less variable than those exerted by fast-twitch units. In addition, the variability among slow-twitch units was relatively constant during the fatigue test while variability among fast-twitch units either increased or decreased with time. 4. For a given motor-unit type, the average time course of force did not depend on whether force in each tetanus was expressed as a peak value, an average peak value, or a force-time integral. 5. Some motor units within each type exhibited potentiation. Most of the variability in the time course of the peak force for each motor-unit type could be accounted for by the potentiating units. Motor units that exhibited only force decline (i.e. fatigue), regardless of unit type, had less variable time courses of peak force. Since potentiation was transient in some unit types, it was assumed that at least two opposing processes (i.e. fatigue and potentiation) occurred simultaneously in these units (see also, Krarup, 1981; Rankin, Enoka, Volz & Stuart, 1988; Garner, Hicks & McComas, 1989). 6. It is concluded that the expression of force potentiation throughout a fatiguing regimen is variable among motor units and that this is not related to conventional motor-unit types. This dissociation suggests that the mechanisms that form the basis for the conventional distinction between motor-unit types are different from those which lead to force potentiation.

Anesthesia, Intravenous↗
PubMed1990

Force development and relaxation in single motor units of adult cats during a standard fatigue test.

1. The purpose of this study was to investigate tetanic force development and relaxation in single motor units that were subjected to a standard fatigue test. 2. Motor units of tibialis posterior, a hindlimb muscle in the adult cat, were assigned to four categories (i.e. types S, FR, FI, FF) using conventional criteria. 3. Based on the first tetanus of the fatigue test, type S units took significantly longer to develop force and to relax than the fast-twitch units. Within the fast-twitch subpopulations, type FR and FI units were significantly slower to develop force and to relax than were type FF units, but there were no significant differences between type FR and FI units. 4. After 120 s of the fatigue test, the rates of force development were faster than initial values in type S and FR units, but were largely unchanged for the type FI and FF units. Most relaxation parameters were unaffected by stimulation in type S and FR units, but all parameters became significantly slower in type FI and FF units. 5. The average time courses of force development and relaxation showed that during 240 s of the fatigue test, type S units exhibited either a progressive increase in a parameter or no change at all. In contrast, fast-twitch units displayed profiles that included initial increases in a force development or relaxation parameter followed by variable amounts of decline that corresponded to fatigability. 6. It is concluded that repetitive activation affects the development and relaxation of tetanic force in all motor-unit types. Average changes in these parameters tended to parallel the conventional classification of motor units into four categories.

Animals↗
PubMed1989

Systemic distribution of apolipoprotein E secreted by grafts of epidermal keratinocytes: implications for epidermal function and gene therapy.

In the present study, human apolipoprotein E (apoE) was monitored in the circulation of athymic mice and rats bearing human epidermal grafts. Human apoE was detected in the systemic circulation of graft-bearing animals as long as the graft remained on the animal. Within 24 hr of graft removal, human apoE was not detectable in plasma, indicating that apoE resulted from continuous production of the protein by grafted keratinocytes. These results show that proteins as large as apoE (299 amino acids) traverse the epidermal-dermal barrier and achieve systemic distribution where they may produce effects on distal tissues. The feasibility of using grafts of genetically-altered keratinocytes for the delivery of secreted proteins is clearly reinforced by the demonstration that an epidermally derived protein exhibits systemic distribution. Finally, by virtue of its systemic distribution, apoE produced in a peripheral tissue such as skin, may function in the reverse transport of cholesterol from peripheral tissues to the liver.

Animals↗
PubMed1989

Synthesis and secretion of apolipoprotein E by cultured human keratinocytes.

Non-polar lipids are synthesized by keratinocytes in the epidermis and transported to the extracellular space where they contribute to formation of a permeability barrier. Transport of non-polar lipids in other organs and tissues usually occurs with the lipid complexed to an apolipoprotein. In this study we set out to learn if apolipoprotein E is produced by human epidermal keratinocytes in culture. Analysis of total cellular RNA from cultured keratinocytes showed the presence of human apolipoprotein E mRNA at concentrations ranging from 2.5 to 35 molecules/cell. The cells secrete a protein identified as apo E on the basis of molecular weight, isoform pattern, and immunoreactivity. Enzyme linked immunosorbent assay of media from keratinocyte cultures indicated that apolipoprotein E is secreted at a rate of 0.92 ng/h/10(6) cells.

Apolipoproteins E↗
PubMed1989

Comparison of intraluminally versus extraluminally administered nimodipine on serotonin-induced cerebral vascular responses in vitro and in situ.

The purpose of our study was to compare the ability of intraluminally and extraluminally administered nimodipine to inhibit serotonin-induced cerebral vascular responses in vitro and in situ. No difference was noted in the ability of nimodipine, whether administered intraluminally or extraluminally, to reduce the contractile response of extraluminally administered serotonin in a closed, pressurized, in vitro bovine middle cerebral artery preparation; histologic studies indicated that the tight endothelial junctions normally found in cerebral arteries remained intact in this preparation. In cats, pretreatment with nimodipine did not significantly reduce the ability of intracisternally injected serotonin to decrease cerebral blood flow; however, nimodipine did reduce the changes in cerebral artery diameter normally noted angiographically after serotonin injection. Although minor differences were noted between the intraluminal and extraluminal routes of administration of nimodipine in situ, in general the effects were comparable.

Animals↗
PubMed1989

Clinical pancreas transplantation. Complete review of eight years experience.

In the eight years since the initiation of pancreas transplantation at our center, 36 patients have received either segmental or whole pancreas grafts. Seventeen patients had segmental pancreas allografts, with eight of these receiving simultaneous kidney allografts from the same donor. Nineteen patients received whole pancreas and kidney allografts. Thirty five of the pancreases were preserved using hypothermic storage for up to 43 hours and 45 minutes, using either albumin-augmented crystalloid or hyperosmolar colloid preservation solution. The one-year actuarial graft survival was 12 per cent for segmental pancreas transplants and 42 per cent for whole pancreas grafts. The use of cyclosporine after whole pancreas transplantation as well as improved surgical techniques for exocrine drainage contributed to the improvement in graft survival in the whole pancreas graft group.

Adult↗
PubMed1988

Estrogen-induced destabilization of yolk precursor protein mRNAs in avian liver.

In addition to regulating gene expression at the level of transcription, estrogen is generally considered to selectively stabilize induced mRNAs against degradation. As a result of mRNA stabilization, estrogen-induced mRNAs accumulate to much higher levels in target cells, and the encoded proteins are made at much greater rates than would occur on the basis of transcriptional activation alone. The present study examined the effect of estrogen on the stabilities of avian liver mRNAs that code for the yolk precursor proteins apolipoprotein (apo) II and vitellogenin (VTG) II. The results show that the degradation rates of apoII and VTG II mRNAs during hormone withdrawal are dramatically altered by the duration of prior estrogen treatment. During the 2 days required for the hormonal inductions of these mRNAs to new steady states, the turnover rates of both mRNAs were the same in the presence and absence of estrogen (t1/2 = 13 h). This result indicates that mRNA stabilization does not contribute to the extensive accumulation of apoII and VTG II mRNAs. When the duration of estrogen treatment was extended beyond 3 days, however, hormone withdrawal led to the rapid (t1/2 = 1.5 h) and selective destabilization of these mRNAs. This result suggests that estrogen induced a destabilization activity that was only functional following hormone withdrawal. Thus, the point at which estrogen alters mRNA stability is at the level of mRNA degradation. An absence of detectable apoII mRNA degradation intermediates during either the slow or rapid mode of mRNA decay suggests that the rate-limiting step for apoII mRNA turnover is an estrogen-sensitive targeting event that marks the mRNA for rapid degradation.

Animals↗
PubMed1988

Association between biochemical and physiological properties in single motor units.

Motor units from the cat tibialis posterior muscle were examined for an association between physiological and biochemical properties. Functionally isolated motor units were categorized on the basis of their physiological properties. This was followed by quantitative microbiochemical analysis of single muscle fibers from each unit, identified in cross sections using the glycogen-depletion method. The activities of malate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase distinguished between fatigable (type FF) and fatigue-resistant (types FR and S) units. The activities of both lactate dehydrogenase and adenylokinase were higher in fast- than in slow-contracting units. Cluster analyses, based on both physiological and biochemical properties or on biochemical properties alone, produced groupings identical to types FF, FR, and S. The association between physiological and biochemical properties substantiates the idea that biochemically distinct groups of motor units correspond to physiologically identifiable groups.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1988

Activation of muscle fibers in individual motor units revealed by 2-deoxyglucose-6-phosphate.

Motor units of the cat tibialis posterior muscle were selectively activated by prolonged electrical stimulation of functionally isolated motor axons in situ. During the activation, the glucose analog 2-deoxyglucose (DG) was administered systemically. Single muscle fibers were subsequently examined for accumulation of the metabolite 2-deoxyglucose-6-phosphate (DG6P) by an analytical assay and for depletion of glycogen by a PAS glycogen-specific staining reaction (periodic acid Schiff; PAS). In general, levels of DG6P were 20 times greater in unstained (PAS-negative) fibers compared with stained (PAS-positive) fibers. However, some glycogen-depleted fibers, particularly in putative ischemic fascicles of the muscle, did not have elevated DG6P, suggesting that depletion of glycogen is not always a reliable indicator of fiber activation. Furthermore, the PAS-staining reaction was not necessarily indicative of quantitative glycogen levels in single fibers. Thus, this report shows that DG6P accumulation enhances the identification of motor-unit fibers selectively activated via their common motor-nerve axon. Evidence is also presented for differential glucose uptake in muscle fibers of different phenotype, thereby indicating that the DG6P measurement in muscle has broad applicability to the investigation of cellular glucose utilization.

Animals↗
PubMed1987

Measurement of axonal conduction velocity in single mammalian motor axons.

In deeply anesthetized cats, determinations of motor-axonal conduction velocity (CV) were made using extracellular potentials recorded from single, functionally isolated motor axons innervating the muscle tibialis posterior. Axons were activated by suprathreshold electrical stimulation at the ventral-root level. Action potentials were recorded with 3 bipolar electrodes located on the muscle nerve at the level of the popliteal fossa. The most proximal and distal of the bipolar muscle-nerve electrodes were 16.4-22.0 mm apart. Estimates were made of CV from ventral root to muscle nerve (conventional CV) and between the proximal and the distal pairs of muscle-nerve electrodes (muscle-nerve CV). An evaluation was based on comparison of these CVs, estimates of uncertainties in time and distance measurements and simulations of the effects of recording conditions on CV estimates. The analysis indicated that the uncertainty in the conventional CV measurement of mammalian motor axons is at least +/- 2%. However, variability may be as great as 20% between muscle-nerve CV measurements from different experiments, probably due to such factors as regional variation in CV and differences in recording configuration.

Action Potentials↗