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S J Sullivan

Publications and source records attributed to S J Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1991

Biohybrid artificial pancreas: long-term implantation studies in diabetic, pancreatectomized dogs.

Diabetic complications such as neuropathy, retinopathy, and renal and cardiovascular disease continue to pose major health risks for diabetic patients. Consequently, much effort has focused on approaches that could replace conventional insulin therapy and provide more precise regulation of blood glucose levels. The biohybrid perfused artificial pancreas was designed to incorporate islet tissue and a selectively permeable membrane that isolates this tissue from the immune system of the recipient. Biohybrid pancreas devices containing canine islet allografts were implanted in ten pancreatectomized dogs requiring 18 to 32 units of injected insulin daily. These implants resulted in good control of fasting glucose levels in six of these animals without further exogenous insulin for periods of up to 5 months.

Animals↗
PubMed1991

Replacement of media in cell culture alters oxygen toxicity: possible role of lipid aldehydes and glutathione transferase in oxygen toxicity.

Replacement of media in cell cultures during exposure to hyperoxia was found to alter oxygen toxicity. Following 100 hr of exposure to 95% or 80% O2, the surviving fraction (SF) of Chinese hamster fibroblasts, as assayed by clonogenicity, was less than 1 x 10(-3) when the culture media was replaced only at the onset of the O2 exposure. Media replacement every 24 hr throughout the hyperoxic exposure resulted in SFs of 1.7 x 10(-1) (95% O2) and 1.9 x 10(-1) (80% O2) at 95 hr. Cellular resistance to and metabolism of 4-hydroxy-2-nonenal (4HNE), a cytotoxic byproduct of lipid peroxidation, was examined in cells 24 hr following exposure to 80% O2 for 144 hr with media replacement. These O2-exposed cells were resistant to 4HNE, requiring 2.6 times as long in 80 microM 4HNE to reach 30% survival as compared to density-matched normoxia control. Furthermore, during 40 and 60 min of exposure to 4HNE, the O2-preexposed cells metabolized greater quantities of 4HNE (fmole/cell) relative to control. The activity of glutathione S-transferase (GST), an enzyme believed to be involved with the detoxification of 4HNE, was significantly increased in the O2-preexposed cells compared with controls. Catalase activity was significantly increased, but no change was found in total glutathione content, glutathione peroxidase, manganese superoxide dismutase, and copper-zinc superoxide dismutase activities at the time of 4HNE treatment in the O2-preexposed cells relative to density-matched control. The results demonstrate that in vitro tolerance to the cytotoxic effects of hyperoxia can be achieved through media replacement during O2 exposure. Tolerance to oxygen toxicity conferred resistance to the cytotoxic effects of 4HNE, possibly through GST-catalyzed detoxification. These results provide further support for the hypothesis that toxic aldehydic byproducts of lipid peroxidation contribute to hyperoxic injury.

Aldehydes↗
PubMed1991

H-reflex modulation during manual muscle massage of human triceps surae.

An investigation of the effect of a six-minute manual muscle massage on the excitability of the spinal reflex pathway in 20 able-bodied subjects was undertaken. H-reflex recordings were obtained from the right soleus muscle, which was the site being massaged. Skin temperature and antagonist activity were monitored in an attempt to explain the changes observed in a previous study. The experimental paradigm chosen was an A-B-A interrupted-time series design consisting of two pretreatment, two treatment (massage), and two posttreatment conditions. H-reflex amplitudes recorded during both massage conditions (.76 +/- .58 mV, .76 +/- .61 mV) were significantly reduced (F5,90 = 69.04, p less than .01) in comparison to all other (before and after) conditions (2.58 +/- .75 mV, 2.56 +/- .71 mV, 2.82 +/- 1.14 mV, and 2.89 +/- .82 mV, respectively). This decrease could not be explained conclusively by changes in skin temperature, nerve conduction velocity, or antagonist recruitment, thus indicating a decrease in spinal reflex excitability attributed to massage. These findings also support our earlier report, which stated that H-reflex amplitudes are reduced only during the period of tissue manipulation, regardless of the duration of the massage.

Adult↗
PubMed1991

Glutathione dependent metabolism and detoxification of 4-hydroxy-2-nonenal.

The involvement of glutathione (GSH) dependent processes in the detoxification of 4-hydroxy-2-nonenal (4HNE) was investigated using Chinese hamster fibroblasts and clonogenic cell survival. GSH reacted, in a dose-dependent fashion, with 4HNE in phosphate buffer at pH 6.5, leading to the disappearance of 4HNE. The addition of glutathione transferase activity (GST) facilitated a more rapid disappearance of 4HNE but the reaction was still dependent on the concentration of GSH. When cell cultures were exposed to the reaction mixtures, 4HNE cytotoxicity was also reduced in a manner which was dependent on the concentration of GSH. When 2.16- or 1.08-mM GSH were incubated in phosphate buffer with 1.08-mM 4HNE in the presence or absence of GST, then mixed with media and placed on cells for 1 h, the cytotoxicity associated with exogenous exposure to free 4HNE was abolished. GSH depletion (greater than 90%) using buthionine sulfoximine (BSO) was accomplished in control (HA1) and H2O2-resistant variants derived from HA1. GSH depletion resulted in enhanced cytotoxicity of 4HNE in all cell lines. This BSO-induced sensitization to 4HNE cytotoxicity was accompanied by a significant reduction in the ability of cells to metabolize 4HNE. The magnitude of the sensitization to 4HNE toxicity caused by GSH depletion was similar to the magnitude of the reduction in the ability of cells to metabolize 4HNE. These results support the hypothesis that GSH and GST provide a biologically significant pathway for protection against aldehydic by-products of lipid peroxidation.

Aldehydes↗
PubMed1991

Effects of massage on alpha motoneuron excitability.

The purpose of this study was to investigate the specificity of the effects of massage (petrissage) on spinal motoneuron excitability as measured by changes in the peak-to-peak amplitude of H-reflex recordings. H-reflexes (and M-responses) were recorded from the distal aspects of the right triceps surae muscle of 8 men and 8 women, aged 20 to 37 years, with no neuromuscular impairments of the lower extremities. The H-reflexes were recorded during five control and four experimental conditions (20 trials at each condition). The control conditions (C1-C5) preceded and followed each experimental condition, providing a measure of the stability of the H-reflex. Each experimental condition consisted of a 4-minute period of massage of the ipsilateral and contralateral triceps surae and hamstring muscle groups (ITS, CTS, IHS, and CHS, respectively). The mean peak-to-peak amplitude of the H-reflex was found to be stable (range = 1.91-1.95 mV) across the five control conditions. H-reflex amplitudes recorded during the experimental conditions indicate that massage of the ITS resulted in a reduction of the H-reflex (0.83 mV) in comparison with the pretest control condition (C1) and the remaining experimental conditions (range = 1.77-2.23 mV). This difference was significant, and subsequent Newman-Keuls tests indicated a specificity of the effects of massage on the muscle group being massaged. [Sullivan SJ, Williams LRT, Seaborne DE, Morelli M. Effects of massage on alpha motoneuron excitability.

Adult↗
PubMed1991

Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas.

Previously the authors reported on a Hybrid Artificial Pancreas device that maintained patent vascular anastomoses in normal dogs and, when seeded with allogeneic canine islets, maintained normal fasting blood sugars (FBS) in diabetic pancreatectomized dogs. Eventual failure of these devices was believed to be related to loss of islet viability and/or insufficient islet mass. The current study evaluates the effect of increased islet mass produced by implantation of two islet-seeded devices in pancreatectomized dogs and compares the results with those from dogs that received a single device. Twelve of fifteen dogs receiving single devices showed initial function as determined by elimination or reduction of exogenous insulin requirement; four showed initial function and seven showed extended function (100 to 284 days). Excessive weight loss (more than 20%), despite normal FBS and insulin dependence, required that four animals in this latter group be killed. Devices seeded with xenogeneic islets have met with limited success. One dog that received two bovine islet-seeded devices achieved function for more than 100 days; the remaining bovine-seeded devices (n = 8) functioned for only 3 to 16 days. Porcine islet-seeded devices were assessed by intravenous glucose tolerance tests (IVGTT). Recipients of two devices seeded with allogeneic islets demonstrated improved IVGTT results when compared to those from pancreatectomized dogs and recipients of single devices but were abnormal when compared to intact animals. Histologic examination of device and autopsy material from all failed experiments was performed and showed no mononuclear cell infiltration of the islet chamber or vascular graft material, only a few incidence of device thrombosis, and varying degrees of islet viability as judged by morphologic and immunohistochemical evaluation. The authors believe they have demonstrated progress toward the development and clinical applicability of the Hybrid Artificial Pancreas.

Animals↗
PubMed1991

Observer variation in assessing neurophysical signs among patients with head injuries.

As an early phase in the development of a valid and reliable measure of the neurophysical sequelae after head injury, we carried out assessments of interrater agreement on representative items. The purpose of this study was to determine the degree of agreement among expert raters who independently measured neurophysical signs on patients undergoing physical rehabilitation after brain injury. Agreement was described using the index of crude agreement, expected agreement and Kappa. Therapists showed a high degree of agreement on those items forming part of a routine neurological assessment: prehension, coordination, voluntary movements and tendon reflexes. Crude agreement ranged from 77.8-100%. There was considerable discordance in assessing muscle tonus, equilibrium and protective reactions, spinal reflexes, tremor and dysmetria (crude agreement ranged from 49.7-97.9%). Although, the number of subjects was small, the information generated from this study will be useful in refining our instrument for the assessment of neurophysical signs.

Adult↗
PubMed1991

Successful treatment of diabetes with the biohybrid artificial pancreas in dogs.

We have investigated a new hybrid artificial pancreas device to transplant islet allografts without immunosuppression. The device consists of a chamber through which passes a copolymer membrane connected to standard vascular grafts. Islets are placed inside the chamber but are outside of the blood stream. Nominal molecular porosity of 80,000 daltons permits free diffusion of nutrients and insulin across the membrane but inhibits the entry of immunoglobulins and immunocytes from the blood stream into the chamber. Initial studies focused on the technical feasibility of implanting the unseeded (no islets) devices. In 12 normal mongrel dogs, the arterial limb of the device was anastomosed end-to-end to the common iliac artery and the venous limb end-to-side to the common iliac vein. Vascular patency was monitored by an audible bruit over the device. Two devices currently remain patent at 388 and 421 days. The remaining experiments failed due to thrombosis and membrane rupture, with 2 failing as late as 170 and 279 days. In a second series, both arterial and venous anastomoses were done end-to-side and dogs were placed on low-dose aspirin therapy. All 8 dogs are currently maintaining patent unseeded devices (96-226 days postimplantation). Subsequent studies determined the function of devices seeded with isolated canine pancreatic islet allografts in totally pancreatectomized, severely diabetic dogs. Diabetes was controlled by once-a-day insulin injection. After 2-3 weeks of diabetic control, a seeded device was implanted. Diabetic control was monitored by fasting blood levels and postprandial and intravenous glucose tolerance tests, and vascular patency by the loudness of the bruit. In the first series of 6 dogs given seeded devices without aspirin, no significant function was discernible, with failure attributable to thrombosis, poor islet viability, and surgical complications. In the second series of 13 dogs given aspirin, 8 dogs have required an appreciably lower dose of injected insulin to maintain fasting blood glucose at acceptable levels. Of note are 4 dogs that required virtually no exogenous insulin for at least 3 weeks. One dog lost function on day 74 and another still requires no insulin at 267 days postimplantation. However, despite normal fasting glucose levels, the glucose tolerance tests showed delayed return to normal levels. Weight lost following pancreatectomy was rapidly regained in the presence of a functioning seeded device. Histologic examination of the removed devices revealed no signs of rejection.

Animals↗
PubMed1991

Changes in hip position modulate soleus H-reflex excitability in man.

The effects of hip flexion and extension on the ipsilateral soleus Hoffmann (H) reflex recruitment curve were studied in 11 healthy subjects. Hip flexion (50 degrees), but not hip extension (15-20 degrees), produced changes in the H-reflex. A maintained facilitation, peaking at intensities of stimulation producing a maximal H-reflex (Hmax), was observed in 6/18 sessions. Inhibition, peaking at intensities submaximal for Hmax, was seen in 7/18 sessions. In some of the latter experiments, there was also a facilitation at high intensities of stimulation (greater than Hmax). The remaining experiments were classified as showing no effect: 3 were unmodulated but 2 showed a facilitation at high intensities of stimulation (greater than Hmax). Since the knee was extended in the test position, a second series of experiments (n = 7) were carried out to determine the possible influence of stretch of the biarticular hamstrings muscle group on the soleus H-reflex by comparing the effects of hip flexion with the knee extended with those obtained when the knee was flexed, thereby relaxing the hamstrings. The results provided no evidence that the variability could be explained by differences in the relative degree of stretch on the hamstrings muscle group. There were, however, systematic variations in the shape of the corresponding control H-reflex recruitment curves between subjects: the mean slope of the rising limb of the recruitment curve was highest in those experiments showing an inhibition, intermediate in the ineffective experiments and lowest in those showing a maintained facilitation. These observations indicate that the reflex output studied was different in the three groups, possibly reflecting differences in the relative proportions of slow- and fast-twitch motor units contributing to the reflex response.

Achilles Tendon↗
PubMed1990

Frequency characteristics of signals and instrumentation: implication for EMG biofeedback studies.

Signals can be analyzed in either the time or frequency domain. In the time domain, the analysis consists of manipulating and measuring one or more characteristics of the signal that may vary with time. One can, for instance, rectify a signal, filter it, calculate its mean value, display the histogram of its amplitude, and so forth. Frequency analysis is less well understood because it requires a lengthy mathematical treatment most easily done by computer. However, it gives exclusive information on a signal. For instance, when the frequency content of a signal is known, it is easy to specify which characteristics an amplifier must have in order to amplify the signal without distortion, or to set the cutoff frequencies of filters to eliminate noise. Also, in many circumstances, frequency spectra are more easily interpreted than the original raw data. Such is the case with the EMG where the random aspect of the signal makes some form of processing (i.e., rectification, filtering, etc.) necessary, but not always as meaningful as we would like. Thus we present here the principal characteristics of frequency analysis, and discuss its usefulness in analyzing EMG signals and its application to biofeedback, clinical practice, and research.

Biofeedback, Psychology↗
PubMed1990

Oxygen toxicity in control and H2O2-resistant Chinese hamster fibroblast cell lines.

Following exposure to 95% oxygen, clonogenic cell survival was assayed and qualitative morphologic changes were observed in a Chinese hamster fibroblast cell line (HA-1). The time in 95% O2 necessary to clonogenically inactivate 90% of the cells was inversely related to the cell density of the cultures at the beginning of hyperoxic exposure (from 1 to 6 X 10(4) cells/cm2). The O2-induced loss in clonogenicity and evidence of morphologic injury were shown to be significantly delayed (17-22 h) in an H2O2-resistant variant of the parental HA-1 cell line. After the delay in onset of clonogenic cell killing or morphologic injury, the process of injury proceeded in a similar fashion in both cell lines. The H2O2-resistant cell line demonstrated significantly greater catalase activity (20-fold), CuZn superoxide dismutase activity (2-fold), and Se-dependent glutathione peroxidase activity (1.5-fold). The greater activities of CuZn superoxide dismutase and catalase were accompanied by similarly greater quantities of immunoreactive protein as determined by immunoblotting. These data demonstrate that the cells adapted and/or selected for growth in a highly peroxidative environment also became refractory to O2-induced toxicity, which may be related to increased expression of antioxidant enzymes. However, the magnitude of this cross-resistance to O2 toxicity was less than the magnitude of the cellular resistance to the toxicity of exogenous H2O2, suggesting that in this system the toxicity of 95% oxygen is not identical to H2O2-mediated cytotoxicity.

Animals↗
PubMed1990

Aerobic and neuromuscular training: effect on the capacity, efficiency, and fatigability of patients with traumatic brain injuries.

To assess the value of exercise training after traumatic brain injury (TBI), 14 sedentary adults with TBI performed a supervised circuit training program three times per week for 16 consecutive weeks. The program was designed to include equal volumes of both aerobic and neuromuscular training to increase the subjects' oxidative capacity and simultaneously improve their locomotor efficiency. Before and after the experimental training program, height, weight, blood pressure, skinfold thickness, grip strength, abdominal muscular endurance, and submaximal and peak rates of oxygen consumption were measured, and the index of physiological fatigue was calculated. The TBI patients manifested subnormal oxidative capacities and above-average oxygen costs locomotion. A 16-week circuit training program of moderate intensity and prolonged duration increased their oxidative capacity (p less than .01) and abdominal muscular endurance (p less than .01), but failed to reduce their oxygen cost of walking. Moderate and prolonged activity seems beneficial in the comprehensive rehabilitation of patients with TBI. The index of physiologic fatigability seems to be useful for the assessment, evaluation, and vocational placement of individuals with TBI.

Adult↗
PubMed1989

Yawning: a possible confounding variable in EMG biofeedback studies.

An elderly hemiplegic patient participating in an EMG biofeedback training program was observed to produce a synergistic flexion movement of the plegic (determined by functional evaluations) upper limb while yawning. In the course of the training sessions the electrical activity of the anterior deltoid (the target muscle) was recorded during yawning. These peak EMG values were greatly facilitated in comparison with the session mean peak values obtained during an attempted maximum voluntary isometric contraction (shoulder flexion) of the same limb (e.g., Trial 1: 85.00 vs. 4.33 microV). The possibility of yawning as a confounding variable in EMG biofeedback studies is presented and discussed.

Aged↗
PubMed1988

Distribution of somatostatin receptors in RINm5F insulinoma cells.

Previous studies with heterogeneous populations of pancreatic cells have provided evidence for the presence of somatostatin (SRIF) receptors in cytosol and secretion vesicles, as well as the plasma membrane. To examine the distribution of SRIF receptors between soluble and membrane fractions in a homogeneous pancreatic islet cell population, we have used the clonal RINm5F insulinoma cell line. These cells contain specific, high affinity binding sites for [125I-Try11]SRIF on the cell surface, and occupancy of these sites by SRIF and SRIF analogs correlates with inhibition of insulin secretion. Stable, steady state binding was achieved using both intact cells and membranes by performing binding incubations with [25I-Tyr11]SRIF at 22 C. Half-maximal inhibition of [125I-Tyr11]SRIF binding occurred with 0.21 +/- 0.11 nM SRIF in membranes and 0.35 +/- 0.30 nM SRIF in cells. In contrast, the binding of [125I-Tyr11]SRIF to cytosolic macromolecules was not reduced by concentrations of SRIF as high as 100 nM, demonstrating that this binding was of much lower affinity. RINm5F membranes were further purified using a Percoll gradient to prepare a microsomal fraction, which was enriched in adenylate cyclase activity, and a secretory granule fraction, which was enriched in insulin. [125I-Tyr11]SRIF binding to the microsomal fraction (3.8 +/- 0.3 fmol/mg) was 3 times higher than to secretion granules (1.2 +/- 0.2 fmol/mg). Thus, high affinity SRIF binding sites were most abundant in microsomal membranes and were low or undetectable in secretory granules and cytosol. To determine whether translocation of SRIF receptors to the plasma membrane accompanied insulin secretion, we examined the effects of various insulin secretagogues on [125I-Tyr11]SRIF binding to intact cells. Leucine (20 mM), glyceraldehyde (15 mM), forskolin (1 microM), and glucagon (1 microM) stimulated insulin release 1.5- to 4.0-fold in different experiments. However, these secretagogues did not increase [125I-Tyr11]SRIF binding. In summary, our results indicate that high affinity SRIF receptors in RINm5F cells are located primarily on the plasma membrane and that the concentration of SRIF receptors at the cell surface is independent of the secretory activity of the cells.

Adenoma, Islet Cell↗
PubMed1987

Changes in short and long latency stretch reflexes prior to movement initiation.

The amplitudes of both short (M1) and long (M2) latency stretch reflexes mechanically elicited in the triceps brachii muscle were investigated prior to its voluntary activitation. The results obtained from 14 healthy subjects indicated that the amplitude of the M2 response increased steadily as the perturbation was delivered closer to the movement suggesting that the M2 changes are associated with the preparation to respond to the visual stimulus. In contrast, the amplitude of the M1 response showed no systematic variations over the same time period. This dissociation of the M1 and M2 reflex responses prior to movement may be attributable to selective gain modulation in supraspinal stretch reflex pathways or to descending projections to polysynaptic spinal pathways.

Adult↗
PubMed1987

Characterization of somatostatin receptors which mediate inhibition of insulin secretion in RINm5F insulinoma cells.

Somatostatin (SRIF) is a neuropeptide which inhibits secretion from a variety of target cells including pancreatic beta-cells. In this study we have used the RINm5F rat insulinoma cell line to characterize high affinity receptors for SRIF. The binding of 0.03 nM [125I-Tyr11]SRIF to RINm5F cells reached a plateau level within 4 h at 37 C at which time 80% of the total binding could be displaced by 100 nM unlabeled SRIF. In contrast, 100 nM concentrations of eight structurally unrelated peptides did not inhibit [125I-Tyr11]SRIF binding. Scatchard analysis indicated that RINm5F cells contained a single class of noninteracting binding sites (910 +/- 190 sites per cell) with high affinity for [125I-Tyr11]SRIF [equilibrium dissociation constant (Kd) = 0.04 +/- 0.01 nM]. Competition experiments with SRIF analogs showed that the binding affinity for [I-Tyr11]SRIF (Kd = 0.03 +/- 0.02 nM) was higher than that for either SRIF (0.24 +/- 0.04 nM) or [Tyr11]SRIF (0.27 +/- 0.04 nM) and that reduced SRIF analogs bound poorly (Kd greater than 50 nM). These results demonstrate that RINm5F cells possess specific, high affinity binding sites for SRIF. Insulin release stimulated by 20 mM leucine or 15 mM glyceraldehyde was inhibited as much as 80% by maximal concentrations (100 nM) of SRIF. The IC50 for SRIF inhibition of leucine-stimulated insulin secretion was 0.43 +/- 0.15 nM, in good agreement with the apparent Kd for binding. In fact, this close correlation between binding affinity and potency to inhibit insulin release was observed for six SRIF analogs, indicating that the characterized binding sites are the receptors which mediate the biological actions of SRIF in RINm5F cells.

Adenoma, Islet Cell↗
PubMed1986

The processing of receptor-bound [125I-Tyr11]somatostatin by RINm5F insulinoma cells.

The peptide somatostatin (SRIF) is secreted by delta cells of the endocrine pancreas and inhibits the secretion of insulin from pancreatic beta cells. We have previously shown that [125I-Tyr11]SRIF binds to specific, high affinity receptors on RINm5F insulinoma cells and that these receptors mediate the action of SRIF to inhibit insulin release. In the present study we investigated the processing of receptor-bound [125I-Tyr11]SRIF in this clonal cell line. Surface-bound and internalized peptides were distinguished by the ability of an acid/salt solution (0.2 M acetic acid, 0.5 M NaCl, pH 2.5) to dissociate only exposed ligand-receptor complexes. Surprisingly, greater than 80% of saturably bound [125I-Tyr11]SRIF was removed by this acid wash independent of the time or temperature of the binding incubation. In contrast, the processing of receptor-bound [125I]EGF (epidermal growth factor) in RINm5F cells was markedly temperature-dependent. Although over 90% of saturably bound [125I]EGF was dissociated by acid after a 4 degrees C binding incubation, less than 10% was removed by acid treatment after 37 degrees C binding. The radioactivity released upon dissociation of receptor-bound [125I-Tyr11]SRIF was analyzed by high performance liquid chromatography and shown to consist of a mixture of intact peptide (40%) and [125I]tyrosine (60%). However, neither the rate of [125I-Tyr11]SRIF dissociation nor its degradation were affected by NH4Cl, methylamine, or leupeptin at concentrations which inhibited the lysosomal degradation of [125I] EGF. Of 11 other protease inhibitors tested, only the metalloendoprotease inhibitor, phosphoramidon, substantially reduced the degradation of receptor-bound [125I-Tyr11]SRIF. These data indicate that, unlike [125I] EGF, receptor-bound [125I-Tyr11]SRIF is not rapidly internalized by RINm5F cells and is degraded by a nonlysosomal process which may involve a metalloendoprotease.

Adenoma, Islet Cell↗