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D Parsons

Publications and source records attributed to D Parsons.

At least 37 records · Page 2Linked to original sources

Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits.

The purpose of this study was to determine whether the reflex hemodynamic responses to static contraction of predominately glycolytic muscle are greater than the changes elicited by primarily oxidative muscle. Low-frequency electrical stimulation (continuous 21 days) of the tibial nerve of one hindlimb of adult rabbits converted the metabolic characteristics of the predominately glycolytic gastrocnemius to a muscle that was primarily oxidative. After 21 days of stimulation, the rabbits were decerebrated, and static contraction of the glycolytic muscle (unstimulated gastrocnemius) initially decreased heart rate (HR; -16 +/- 3 beats/min) and mean arterial pressure (MAP; -17 +/- 3 mmHg). Thereafter, MAP increased 13 +/- 3 mmHg above baseline. Static contraction of the oxidative muscle (stimulated gastrocnemius) produced similar decreases in HR and MAP (-12 +/- 4 beats/min and -12 +/- 3 mmHg, respectively). However, the subsequent increase in MAP (8 +/- 3 mmHg; above baseline) was less than that evoked by contraction of the glycolytic muscle. The responses evoked by stretch of each muscle and high-intensity electrical stimulation were the same, indicating that the afferents from the muscle were not destroyed by the chronic-stimulation technique. These results support the hypothesis that metabolic by-products play a role in the pressor response to static contraction of skeletal muscle. In addition, these data confirm that contraction of predominately oxidative muscle can evoke a reflex pressor response, albeit smaller than the change elicited from primarily glycolytic muscle.

Analysis of Variance↗

Interaction of Staphylococcus aureus with human neutrophils and the down-regulation of TNF receptors.

We have shown previously that pre-exposure of neutrophils to TNF significantly enhanced their killing of opsonized Staphylococcus aureus. We now demonstrate that the ability of TNF to enhance the bactericidal activity is dependent on preincubation time; enhancement was still evident when TNF and bacteria were added simultaneously to neutrophils but if TNF addition was delayed by 5 min, no enhancement was seen. Evidence is presented that suggests that this could be related to a down-regulation of TNF receptors by the bacteria, but in addition, the release of TNF receptor fragments may contribute to the inhibition observed. Scatchard analyses demonstrated a decrease from approximately 3000 TNF receptor (receptor binding) sites per cell to 450 following treatment with S. aureus, but essentially no change in receptor affinity. Using mAb directed against the type A (75 kDa) receptor (utr-1) and the type B (55 kDa) receptor (htr-9), it was found that the expression of both receptors was decreased following treatment with the bacteria. The time course of loss of these receptors showed that the surface expression of both molecules was markedly decreased by 5 min which correlated with the loss in ability of TNF to enhance the bactericidal activity. In contrast to changes seen in the binding of TNF, similarly treated neutrophils showed essentially no change in the binding of radiolabeled tripeptide FMLP and, if anything, an increase in the expression of the CD11b Ag (CR3 receptor). When another phagocytic stimulus was used, opsonized fungi (Torulopsis glabrata), a similar depression of TNF binding was also found, but opsonized sheep erythrocytes had no effect on the TNF binding, suggesting that the effects on the TNF receptor cannot be explained simply on the basis of particle phagocytosis.

Down-Regulation↗

Geometric problems in molecular biology and robotics.

Some of the geometric problems of interest to molecular biologists have macroscopic analogues in the field of robotics. Two examples of such analogies are those between protein docking and model-based perception, and between ring closure and inverse kinematics. Molecular dynamics simulation, too, has much in common with the study of robot dynamics. In this paper we give a brief survey of recent work on these and related problems.

Animals↗

Killing of Staphylococcus aureus by tumor necrosis factor-alpha-activated neutrophils. The role of serum opsonins, integrin receptors, respiratory burst, and degranulation.

We have examined the effects of TNF priming on the killing of Staphylococcus aureus by human neutrophils. In the absence of serum opsonins, neutrophils failed to kill S. aureus, and TNF priming did not induce the cells to become bactericidal. Normal human serum, containing complement activity, promoted the killing of the bacteria by neutrophils. Pretreatment of neutrophils for 30 min with TNF significantly enhanced their bactericidal activity. The effects of TNF on neutrophil bactericidal activity was dependent on serum concentration and the degree of enhancement induced increased up to a concentration of 1%. The kinetics of bacterial killing showed that TNF-only enhanced the initial rate of killing, over the first 30 min. Little killing of bacteria occurred in the presence of complement-inactivated serum, and TNF did not stimulate this killing. These results suggest that TNF enhances the neutrophil complement-dependent killing of S. aureus. TNF increased the expression of CR3 (CD11b/CD18) and CR4 (P150, 95; CD11c/CD18) adhesion receptors but not LFA-1 (CD11a/CD18); and mAb against the alpha-chain of either CR3 or CR4 but not LFA-1 prevented the enhancing effects of TNF on the neutrophil bactericidal activity.

Animals↗

Characterisation of an infectious bronchitis virus isolated from vaccinated broiler breeder flocks.

Four apparently serologically closely related isolates of infectious bronchitis virus were obtained from two flocks of vaccinated broiler breeders, one mile apart, which were experiencing increased mortality and decreases in egg production. The isolates were serologically distinct from isolates previously described and capable of causing characteristic infectious bronchitis-like respiratory infection in young chicks. In one experiment, the H120 vaccine strain of the virus did not protect the trachea against challenge with the new isolates 21 days later.

Animals↗

Impedance plethysmography and thrombo-embolic disease.

This study compares the results of impedance plethysmography with lower limb venography in 68 patients referred for investigation of clinical deep vein thrombosis, and with the results of ventilation/perfusion isotope scans in 125 patients with suspected pulmonary embolism. Impedance plethysmography had a sensitivity of 100% and a specificity of 61% for the detection of thromboses involving popliteal or more proximal veins (30 patients), but a sensitivity of 90% and a specificity of 68% in the detection of thrombosis at any level, because of a low sensitivity in the detection of isolated calf vein thrombosis (60% in 10 patients). It is a non-invasive, portable and low-cost technique and, in centres where anticoagulation is only given to patients with popliteal or more proximal thrombosis, venography may only be necessary if impedance plethysmography is positive. It may also be of value in the assessment of patients with suspected pulmonary embolic disease and an indeterminate ventilation/perfusion lung scan.

Humans↗

Reduced exercise capacity in senescent beagles: an evaluation of the periphery.

This study investigated the effect of age on peripheral factors involved in the systemic response to maximal exercise. Skeletal muscle was analyzed and regional blood flow distribution was determined at rest and during maximal exercise in senescent (old) and in younger mature (young) beagles. Maximal exercise capacity was significantly reduced (P less than 0.05) in old and was associated with a reduction in cardiac output (CO), as well as a tendency for arteriovenous O2 difference to be reduced, with a concomitant reduction in maximal O2 consumption. In each regional circulation evaluated, resting blood flow was similar in young and old. During exercise, blood flow was similar in young and old to the diaphragm, heart, tongue, and six of seven locomotory muscles. Concomitant blood flow reductions in splanchnic regions tended to be more pronounced in old than in young. Skeletal muscle analyses of triceps, semitendinosus, and gastrocnemius muscles disclosed similar percent fiber type distribution in young and old but a reduction in type II fiber area in old. In addition, both muscle capillary density and capillary-to-fiber ratio were reduced in old. These results demonstrate that age-related changes in blood flow distribution during maximal exercise enable skeletal muscle blood flow to be maintained in old, despite reductions in maximal CO and in muscle capillary density. However, this pattern of blood flow distribution only partially compensates for the combined effects of age-related changes in metabolic potential of the periphery, O2 content of arterial blood, and cardiac function during maximal exercise in old.

Aging↗

Design and implementation of a new computerized system for intraoperative cardiac mapping.

A rapid, portable, yet inexpensive and expandable computer-based system utilizing current technology has been developed from experience in the operating room. An efficient operating system well suited for surgery is defined. New technology recording arrays fabricated from multielectrode flexible Kapton strips were developed and found to be easy to use and highly reliable. Novel arrays are created easily for research or special clinical applications. The system displays all incoming data in real time and transfers 16-s epochs to disk on command. After the user defines a beat for analysis, the computer determines the activation time for each channel, rejects unsatisfactory channels, and displays the results for review and modification before plotting the isochronal map on the monitor. The average time to recall data and produce a map is 16 s; if manual review of 120 channels is included, mapping time is less than 4 min. Clinical data recorded during surgery are discussed. The speed and operational ease demonstrated in the operating room make this computer/electrode system valuable both for surgery and for elucidating basic mechanisms of arrhythmias.

Algorithms↗

Anoxic hepatocyte injury: role of reversible changes in elemental content and distribution.

Examination of anoxic isolated hepatocytes by light and electron microscopy indicated that initial morphologic changes were largely localized to the periphery of the cells. This early phase consisted of surface bleb formation but was not accompanied by alterations in parameters of plasma membrane integrity (leakage of cellular enzymes, exclusion of trypan blue). The time course of changes in structure was temporally related to alterations in the elemental distribution and content of various subcellular compartments. These studies, which employed electron probe X-ray microanalysis, demonstrated that rapid increases in the sodium and chlorine content and decreases in the potassium content of the cytoplasm, mitochondria and nucleus occurred, whereas no change in the calcium content of any subcellular compartment was detected. Concurrently, two cellular functions known to be dependent upon ion homeostasis, sodium-dependent taurocholate uptake and mitochondrial respiratory control, became markedly impaired. Reoxygenation within 30 min resulted in the restoration of both elemental distribution and the latter two functions to baseline. These data are consistent with the hypothesis that some early functional changes may be mediated by altered ion homeostasis. In contrast, additional studies indicated that sodium and water fluxes could be dissociated from the appearance of plasma membrane blebs. Thus, this study provides direct evidence that the structural and functional changes of early anoxic hepatocyte injury cannot be explained by a single mechanistic cascade, but apparently involve multiple mechanisms which may not be directly linked.

Animals↗

Tension and electrolyte changes with Na+-K+ pump inhibition in rat papillary muscle.

Myocardial ischemic injury results in altered membrane integrity, energy depletion, and electrolyte shifts leading to accumulation of intracellular Ca. However, analysis of the direct effects of Ca accumulation is complicated by other concomitant cellular changes produced by ischemia. The purpose of this study was to examine the effects of Ca loading in rat papillary muscles produced by Na+-K+ pump inhibition in oxygenated K+-free buffer. Changes in contractile characteristics, high energy phosphate, and elemental concentrations of subcellular compartments were measured. Electron probe X-ray microanalysis was used to assess elemental concentrations in cryosections. After 3 h of Na+-K+ pump inhibition, resting tension (RT) increased to 164% and developed tension (DT) fell to 16.8% of control values. One hour after return to complete buffer, RT and DT partially recovered but remained significantly different from the 180 to 240-min values for the control muscles. Electron probe X-ray microanalysis showed increases in cytoplasmic and mitochondrial Na and Ca and a decrease in K during Na+-K+ pump inhibition. Mitochondrial Ca was greater than 100-fold greater than Ca in control mitochondria. Morphologically, the majority of cells showed ultrastructural damage. The mean ATP level was 20% of control. After 1 h of recovery, the cells appeared more heterogeneous, and the mean mitochondrial Ca decreased, whereas mean cytoplasmic Ca increased. Further statistical analysis showed a bimodal distribution for Na, Ca, K, Mg, and Cl, which coincided with the morphologically mixed population of cells. This suggests that replacement of extracellular K+ was associated with restored electrolyte gradients in some cells and the persistent or further alteration of electrolytes in others. These results suggest that variable Ca accumulation and associated ATP depletion without the compounding effects of ischemia lead to cell injury similar to reperfusion injury reported in ischemic myocardium.

Adenosine Triphosphate↗

Three-dimensional reconstruction of cells from serial sections and whole-cell mounts using multilevel contouring of stereo micrographs.

A comprehensive computer-graphics-based system (STERECON) is described for tracing and digitizing contours from individual or stereopair electron micrographs. The contours are drawn in parallel planes within the micrographs. Provision is also made for tracing and digitizing in full three-dimensional (3-D) coordinates in any direction along linear structures such as cytoskeletal elements. The stereopair micrographs are viewed in combination with the contours being traced on a graphics terminal monitor. This is done either by projecting original electron micrograph (EM) negatives onto a screen and optically combining these images with contour lines being drawn on the monitor, or by first digitizing the images and displaying them directly on the monitor along with the contour lines. Prior image digitization allows computer enhancement of the structures to be contoured. Correction and alignment routines are included to deal with variable section thickness, section distortion and mass loss, variations in photography in the electron microscope, and terminal screen curvature when combining projected images with contour lines on the monitor. The STERECON system organizes and displays the digitized data from successive sections as a 3-D reconstruction. Reconstructions can be viewed in any orientation as contour stacks with hidden lines removed; as wire-frame models; or as shaded, solid models with variable lighting, transparency, and reflectivity. Volumes and surface areas of the reconstructed objects can be determined. Particular attention was paid to making the system convenient for the biological user. Users are given a choice of three different stereo-viewing methods.

Animals↗