Search PubMed⌕ Search

Biomedical subjects

S J Sullivan

Publications and source records attributed to S J Sullivan.

At least 73 records · Page 4Linked to original sources
PubMed1984

Asymmetric distribution of the chemotactic peptide receptor on polymorphonuclear leukocytes.

The distribution of chemotactic peptide receptors on polymorphonuclear leukocytes (PMNs) was visualized using tritiated chemotactic peptide, N-formylmethionyl-leucylphenylalanine, coupled to hemocyanin (HY-FMLP). This probe was biologically active and the number of HY-FMLP molecules bound to the cell in a saturable manner corresponded closely to the number of peptide receptors characterized for rabbit peritoneal polymorphonuclear leukocytes (Sullivan, S. J., and S. H. Zigmond, 1980, J. Cell Biol., 85:703-711). Cells exhibiting locomotion have a polar morphology easily recognized in the scanning electron microscope. HY-FMLP bound to these cells was asymmetrically distributed with the highest density of HY-FMLP bound to the midregion of the cell. There were very few particles bound to the tail regions. The binding to the leading ruffles was variable but usually less than to the midregion. Addition of high concentrations of uncoupled FMLP eliminated HY-FMLP binding, confirming that the hemocyanin observed was a marker for the saturable chemotactic peptide receptor. The asymmetry in receptor distribution was seen on cells that had been stimulated by low concentrations of either FMLP or another chemotactic factor, leukotriene B4. Thus, peptide binding to the receptor was not required for the development of the asymmetric distribution. The low density of receptors in the tail region of the cell was consistent with the decreased responsiveness of the tail to chemotactic stimulation (Zigmond, S. H., H. I. Levitsky, and B. J. Kreel, 1981, J. Cell Biol., 89:585-592). The receptor asymmetry may contribute to the polar behavior exhibited by polymorphonuclear leukocytes and would be expected to quantitatively modify the directional information available to a cell in a gradient of chemotactic peptide.

Animals↗
PubMed1982

Kinetic analysis of chemotactic peptide receptor modulation.

The dynamics of the chemotactic peptide receptor on rabbit peritoneal polymorphonuclear leucocytes were followed using the tritiated peptide N-formylnorleucylleucylphenylalanine (FNLLP). We have used a kinetic analysis to examine the possible interrelationships between receptor loss (down-regulation), receptor-mediated peptide uptake, and receptor recycling. We have previously demonstrated that cells incubated with FNLLP show a dose-dependent reduction in the number of receptors available on the surface. This receptor down-regulation is complete within 20 min and then the number of receptors available for binding remains at a plateau level. Peptide continues to be taken up in a receptor-mediated manner even after down-regulation is complete. If peptide is removed, receptor recovery occurs and does not require protein synthesis. In these studies we have investigated the kinetics of these processes. On the basis of this analysis, we propose that the plateau receptor level is a steady-state in which receptor internalization and return occur continuously. We demonstrate that the rate of receptor-mediated peptide uptake is approximately equal to the rate of receptor recovery measured after peptide removal. In addition, the rate of receptor recovery is proportional to the number of receptors missing from the surface, suggesting receptor recycling may be occurring.

Animals↗
PubMed1980

Chemotactic peptide receptor modulation in polymorphonuclear leukocytes.

The binding of the chemotactic peptide N-formylnorleucylleucylphenylalanine (FNLLP) to its receptor on rabbit polymorphonuclear leukocytes (PMNs) modulates the number of available peptide receptors. Incubation with FNLLP decreases subsequent binding capacity, a phenomenon that has been termed receptor down regulation. Down regulation of the chemotactic peptide receptor is concentration dependent in both the rate and extent of receptor loss. The dose response parallels that of FNLLP binding to the recptor. The time-course is rapid; even at concentrations of FNLLP as low as 3 x 10(-9) M, the new equilibrium concentration of receptors is reached within 15 min. Down regulation is temperature dependent, but does occur even at 4 degrees C. Concomitant with down regulation, some of the peptide becomes irreversibly cell associated. At 4 degrees C, there is a small accumulation of nondissociable peptide that rapidly reaches a plateau. At higher temperatures, accumulation of nondissociable peptide continues after the rceptor number has reached equilibrium, and the amount accumulated can exceed the initial number of receptors by as much as 300%. The dose response of peptide uptake at 37 degrees C reflects that of binding, suggesting that it is receptor mediated. This uptake may occur via a pinocytosis mechanism. Although PMNs have not been considered to be pinocytic, the addition of FNLLP causes a fourfold stimulation of the rate of pinocytosis as measured by the uptake of [3H]sucrose.

Adaptation, Physiological↗
PubMed1979

Sensory adaptation of leukocytes to chemotactic peptides.

The morphology and behavior of polymorphonuclear leukocytes (PMNs) were studied after rapid changes in the concentration of a chemotactic factor N-formylnorleucylleucylphenylalanine (f-NorleuLeuPhe) (Schiffmann et al., 1975, Proc. Natl. Acad. Sci. U. S. A. 72:1059--1062). After an increase in peptide concentration, the cells round, form lamellipodia or ruffles over most of their surface, and stop locomotion. These changes are transient. After a delay, the cells, still in the presence of peptide, withdraw most of the ruffles and resume locomotion, forming ruffles only at their front. Cells repeat the transient generalized ruffling upon further increase in peptide concentration. The behavioral changes occur over the same dose range as binding to a saturable receptor. The duration of the transient response after a concentration increase is roughly proportional to the increase in the number of cell receptors occupied as a result of the concentration change. Decreasing the concentration of peptide causes the cells to round transiently and form blebs before they recommence locomotion. The transient nature of these aspects of the cell's responsiveness to chemotactic factors appears to be due to adaptation by the cells. The ability to adapt to the concentration of a chemotactic factor may be important in leukocyte chemotaxis.

Adaptation, Biological↗
PubMed1973

Metabolic regulation by homoserine in Escherichia coli B-r.

A mathematical analysis of branched pathway regulation has led to the prediction of a novel homoserine control in Escherichia coli B. Experimental support for such control is presented in this paper. Homoserine, the precursor of both threonine and methionine, inhibits nicotinamide adenine dinucleotide phosphate (NADP(+))-specific glutamate dehydrogenase (EC 1.4.1.4), the enzyme catalyzing the first reaction in ammonia assimilation. Physiological and biochemical evidence for this effect are offered. Homoserine depresses the growth rate of the organism, and glutamate, the product of the inhibited reaction, reverses this effect. The NADP(+)-specific glutamate dehydrogenase activity in cell-free extracts is inhibited by homoserine, and this inhibition parallels the restriction of growth rate. These effects are found in other enteric bacteria which share a similar overall pattern of control for the amino acids derived from aspartate. On the other hand, a sampling of more distantly related species which have different pathways and/or regulatory patterns provides no evidence for homoserine inhibition of the glutamate dehydrogenase reaction.

Aspartate Aminotransferases↗
PubMedDate not supplied

Evaluation of the hybrid artificial pancreas in diabetic dogs.

Immunoisolation of nonsyngeneic tissue using a selectively permeable membrane is designed to facilitate transplantation without the use of immunosuppression. The authors' studies have evaluated a hybrid artificial pancreas device that is implanted as an arteriovenous vascular shunt. Devices containing allogeneic or xenogeneic islets were implanted in diabetic dogs who had undergone pancreatectomies, and the devices eliminated the requirement for exogenous insulin for control of fasting glycemia in 11 animals for periods ranging from 1 to 8 months. Furthermore, unseeded devices in normal dogs have been shown to remain patent for over 2 years with low doses of aspirin as the only anticoagulant. These results indicate that this approach has potential as a therapy for diabetes.

Animals↗
PubMedDate not supplied

Islet transplantation using an immunoprotective membrane in dogs that have undergone a pancreatectomy.

The use of a selectively permeable membrane to transplant nonsyngeneic tissue without accompanying immunosuppressive therapy has been investigated using two approaches. The first hybrid artificial pancreas is implanted as a vascular shunt in which blood circulates through the lumen of a tubular membrane. The islet tissue is distributed within a chamber surrounding the membrane enclosed by an acrylic housing. Studies with diabetic dogs that have had pancreatectomies have demonstrated that these devices could replace exogenous insulin therapy for at least 6 months in five animals. This report presents data on two of these dogs, demonstrating viability and function of the transplanted tissue after 1 year. As an alternative to the vascular device, islets sealed within cylindrical permselective membrane chambers have been implanted in the peritoneum. Preliminary data from three dogs indicate that the nonvascular implants can also regulate fasting glucose levels in the diabetic dog model.

Animals↗
PubMedDate not supplied

In vitro characterization of porcine hepatocyte function.

The clinical consequences of acute liver failure are associated with high mortality. Intensive medical intervention is required to treat the symptoms of liver failure, including coagulopathy, metabolic instability, and encephalopathy. Providing temporary liver support with an extracorporeal liver assist device could stabilize the patient until a donor liver became available or the patient's own liver was able to recover. The use of human hepatocytes as the biologic component of the assist device is precluded by the scarcity of available tissue and the limited proliferative potential of adult hepatocytes in vitro. Consequently, porcine hepatocytes are being evaluated as a cell source for liver assist devices. Maintaining differentiated function in isolated hepatocytes, however, remains a challenge in the development of this technology and is complicated by the fact that the key therapeutic functions for short-term survival have not been well defined. Several approaches have been effective in prolonging rodent hepatocyte function in vitro, including manipulation of extracellular matrix. Here, we have investigated porcine hepatocyte function in vitro with a specific emphasis on the response to exogenous collagen matrix. In control cultures, albumin secretion increased during the first 7-10 days of culture to an average of 50 +/- 17 microg/day/10(6) cells and then decreased over the next 2 weeks. The pattern of urea synthesis was slightly different in that it was highest in the first 1-3 days postisolation (140 +/- 19 microg/day/10(6) cells) and then decreased by about 50% to a plateau level that was stable during the next 3-4 weeks of culture. Cytochrome P450-mediated activities were the most labile with time in culture and were undetectable after the first week in the absence of pharmacological inducers. In contrast to results reported for rat cells, porcine hepatocytes exhibited differentiated function in the absence of any modification of the culture dish surface and function was not increased or prolonged in the presence of exogenous collagen.

Albumins↗
PubMedDate not supplied

The role of and possibilities for physical conditioning programmes in the rehabilitation of traumatically brain-injured persons.

The development of rehabilitation programmes for traumatically brain-injured persons is a complex and multidisciplinary effort. One aspect of such programmes is the development of physical work capacity via exercise or physical conditioning. This paper reviews literature dealing with the physical work capacity following traumatic brain injury and its responses to training. The incorporation of physical activity into a specific rehabilitation programme is described and the possible roles of exercise in the rehabilitation programme are discussed.

Adolescent↗
PubMedDate not supplied

Prediction of motor status 3 and 6 months post severe traumatic brain injury: a preliminary study.

The prediction of outcome following severe traumatic brain injury has received considerable attention in recent years. Previous prediction studies have focused on a long-term follow-up or prediction period. The reported outcome measures generally adopted a global approach (e.g. independent living) in terms of the prediction of physical function. The objective of the present study was to construct clinically useful predictive equations of motor system status, as represented by selected postural reactions (indicators of central nervous system function). Specifically, these equations would serve to predict the recovery of equilibrium and protective reactions both at 3 and 6 months post-injury, respectively. A stepwise multiple logistic regression analysis was performed, where nine predictive variables were considered using a multivariate approach. The results indicate that coma duration followed by age contribute significantly to the predictive capability of the models at both 3 and 6 months post-injury. Specifically, at 3 months, the predictive variables 'coma duration' and 'age' enabled an 84.62% correct prediction rate, whereas, at 6 months, 'coma duration' and 'age' enabled a 79.49% correct prediction rate. In addition, the exact probabilities (for given sample ages and coma durations) and associated 95% confidence intervals were calculated based on the predictive models obtained. The theoretical framework underlying these predictive models can form the basis for further studies. Furthermore, these preliminary predictive models have potential implications for early treatment planning and patient management.

Adult↗
PubMedDate not supplied

Expert opinion in the identification of variables for the measurement of early recovery in adults with traumatic brain injury.

The expert opinion of 27 experienced physical therapists was systematically sought using a modified Delphi technique in order to identify the important variables to be included in the neurophysical evaluation of the traumatic brain-injured (TBI) adult during the acute stage of rehabilitation (first 3 months). An initial survey of the therapists generated 63 items which were later regrouped into 23 categories. Each category was then rated using a five-point scale (1 = of no importance to 5 = extremely important) by each therapist as to its importance in the early clinical neurophysical evaluation of the TBI patient. Those variables identified as extremely important by at least 50% of experts include: state of consciousness, voluntary movements, spontaneous movement and transfers. The results of this study highlight, for physical therapists and other health professionals, the important variables to be included in the evaluation of neurophysical deficits in persons with TBI in the acute stage of rehabilitation.

Adult↗
PubMedDate not supplied

Persistent vegetative state: which sensory-motor variables should the physiotherapist measure?

This study used a modified Delphi technique to establish a list of core items which should be included in the measurement, by the physical therapist, of sensory-motor capacities of persons in a persistent vegetative state. Twenty-eight physical therapists with a mean of 5.9 years of experience working with this clientele participated in the study and identified 105 items as being important in the evaluation of the PVS patient (Round I). The study planning committee reduced these to 20 categories and asked the therapists to rate each category of items (a 5-point scale) as to it's importance (Round II). Physiotherapists identified 14 variables as being 'extremely' or 'very important' to include in such an evaluation. These included: tonus, voluntary movement on request, postural reactions, passive range of motion, tolerance to verticalization and postural status. These results are being used to develop a quantitative assessment instrument to be used by the physical therapist working with the PVS patient.

Arousal↗
PubMedDate not supplied

Diadochokinetic rate in persons with traumatic brain injury.

This study examined diadochokinetic rate (DR) performance in a group of 28 traumatically brain injured (TBI) patients and their matched controls for 16 different articulatory positions in order to determine which articulatory positions distinguished between the two groups. Discriminant function analysis determined (p = 0.000) four variables ('ta', 'ba', 'da' and 'ch') as resulting in the successful classification of 82.2% of the subjects. This implies that this subset of variables is adequate for determining DR in this population. The test-retest reliability (ICC) was also established in a group of 12 subjects and their matched controls. The ICCs ranged from 0.12 to 0.93 for the TBI subjects with 13 of 16 variables > 0.60.

Adolescent↗
PubMedDate not supplied

Do cutaneous receptors contribute to the changes in the amplitude of the H-reflex during massage?

Massage is known to produce a reduction in spinal reflex excitability. However, the mechanisms subserving this phenomenon have yet to be elucidated. This study was undertaken to determine the role of superficial cutaneoreceptors overlying the triceps surae during the application of a massage. Twelve neurologically healthy volunteers were subjected to an interrupted repeated measures design consisting of eight conditions. Each condition was comprised of eleven H-reflex recordings obtained from the right soleus muscle. Six conditions served to establish baseline control levels, while the remaining two conditions consisted of reflex recordings obtained simultaneous to the application of the massage. During the first massage condition, subjects were at rest while a three minute petrissage was applied to the right triceps surae muscle group. The second massage condition was always preceded by the application of a topical anaesthetic to abolish the sensation to touch and pin-prick to the skin area that was to be massaged. It was expected that the cutaneous afferents would not play any major role in the changes associated with the application of the massage. H-reflex amplitudes recorded during each massage condition (1.20 mV +/- 0.30 SEM, 1.05 mV +/- 0.23 SEM, respectively) were significantly reduced (F7.77 = 26.048, p < 0.01) in contrast to all control conditions (range: 2.21 to 2.63 mV). However, no difference was observed between the two massage conditions. The inhibitory effects of massage on the soleus H-reflex do not appear to originate from mechanical stimulation of cutaneous mechanoreceptors. It seems more likely that deep mechanoreceptors are involved.

Adult↗