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S R Hall

Publications and source records attributed to S R Hall.

At least 19 recordsLinked to original sources
PubMed2006

Physical structure of lakes constrains epidemics in Daphnia populations.

Parasites are integral parts of most ecosystems, yet attention has only recently focused on how community structure and abiotic factors impact host-parasite interactions. In lakes, both factors are influenced by habitat morphology. To investigate the role of habitat structure in mediating parasitism in the plankton, we quantified timing and prevalence of a common microparasite (Metschnikowia bicuspidata) in its host, Daphnia dentifera, in 18 lakes that vary in basin size and shape. Over three years, we found substantial spatial and temporal variation in the severity of epidemics. Although infection rates reached as high as 50% in some lakes, they did not occur in most lakes in most years. Host density, often considered to be a key determinant of disease spread, did not explain a significant amount of variation in the occurrence of epidemics. Furthermore, host resistance does not fully explain this parasite's distribution, since we easily infected hosts in the laboratory. Rather, basin shape predicted epidemics well; epidemics occurred only in lakes with steep-sided basins. In these lakes, the magnitude of epidemics varied with year. We suggest that biological (predation) and physical (turbulence) effects of basin shape interact with annual weather patterns to determine the regional distribution of this parasite.

Animal Diseases↗
PubMed2001

Schiff base-mediated co-stimulation primes the T-cell-receptor-dependent calcium signalling pathway in CD4 T cells.

In addition to macromolecular interactions that provide co-stimulation during antigen-presenting cell (APC) and CD4+ T-cell conjugation, covalent chemical events between specialized ligands have been implicated in T-cell co-stimulation. These take the form of transient Schiff base formation between carbonyls and amines expressed on APC and T-cell surfaces. Small Schiff base-forming molecules, such as tucaresol, can substitute for the physiological donor of carbonyl groups and provide co-stimulation to T cells, thereby functioning as orally active immunopotentiatory drugs. The Schiff base co-stimulatory pathway in T cells has been partially characterized in terms of changes in Na+ and K+ transport, and activation of the mitogen activated protein kinase (MAPK) ERK2. In the present study, the effects of Schiff base co-stimulation by tucaresol on the T-cell receptor (TCR)-dependent pathway leading to Ca2+ release were investigated. Schiff base co-stimulation by tucaresol was found to prime for enhanced TCR-dependent phospholipase C-gamma phosphorylation, inositol 1,4,5-triphosphate production, and Ca2+ mobilization that correlated with functional enhancement of interleukin-2 production in primary T cells. The effects on Ca2+ occurred comparably in Jurkat and primary CD4+ T cells responding to anti-CD3 monoclonal antibody. Enhancement of the Ca2+ response required a 10-min priming period and was prevented by prior covalent ligation of cell-surface free amino groups by sulpho-N-hydroxy succinimido-biotin; clofilium-mediated inhibition of tucaresol-induced changes in intracellular K+; and selective inhibition of the MAPK pathway. The data are consistent with a priming mechanism in which late co-stimulation-triggered events exert a positive influence on early TCR-triggered events. In additional studies of murine T cells expressing trans-gene TCRs, tucaresol was likewise shown to prime for enhanced Ca2+ mobilization in response to physiological TCR-engagement by MHC-peptide complexes.

Amines↗
PubMed2001

The release of spinal prostaglandin E2 and the effect of nitric oxide synthetase inhibition during strychnine-induced allodynia.

The removal of spinal glycinergic inhibition by intrathecal strychnine produces an allodynia-like state in rodents. Our objective was to measure spinal prostaglandin E2 (PGE2) release during strychnine-allodynia and examine the effects of Nomega-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthetase. Under halothane, rats were fitted with intrathecal and spinal microdialysis catheters, and microelectrodes implanted into the locus coeruleus for measurement of catechol oxidation current (CAOC) using voltammetry. Animals were then administered urethane and treated as follows: 1) baseline control 10 min, intrathecal strychnine (40 microg) 10 min, 10 min of hair deflection, and 2) 10-min control followed by intrathecal strychnine (40 microg) with hair deflection for 60 min. Spinal dialysate samples were collected for PGE2 levels determined by using immunoassay. In separate experiments, the effect of intrathecal strychnine (40 microg) followed by hair deflection was studied in rats pretreated with intrathecal l-NOARG (50 nmol). After intrathecal strychnine, hair deflection significantly increased spinal PGE2 release (619% +/- 143%), locus coeruleus CAOC (181% +/- 6%), and mean arterial pressure (123% +/- 2%) P < 0.05. Pretreatment with intrathecal l-NOARG significantly inhibited strychnine-allodynia. In this model, hair deflection evokes spinal PGE2 release, locus coeruleus activation, and an increase in mean arterial pressure. L-NOARG pretreatment attenuated the locus coeruleus CAOC, a biochemical index of strychnine-allodynia, suggesting a mediator role of nitric oxide. A mediator role of nitric oxide is also implicated, helping to explain the pathophysiology of this allodynic pain.

Animals↗
PubMed2001

Synthesis and structure of, and bonding in some derivatives of 2,6,9,10-tetraoxatricyclo[3.3.1.1(3,8)]-decane.

Five derivatives of 2,6,9,10-tetraoxatricyclo[3.3.1.1(3,8)]decane were synthesized and their molecular structures in the solid state were determined by means of X-ray diffraction analysis. In addition, the structures of all the molecules were optimized at different levels of computational quantum chemistry (HF/6-31G*, B3LYP/6-31G*). Experimentally determined bond lengths were compared with their calculated counterparts, and striking differences between the Hartree-Fock (HF) results and the experimental data could be traced back to the lack of correlation energy in the geometry optimizations. Two of the compounds under consideration are diastereomers and their relative stability was not only calculated with a conventional ab initio method (ZPE+MP2/6-31G*//HF/6-31G*), but also within the framework of density functional theory (B3LYP/6-31G*). In some of the calculations the influence of the solvent was included in single point calculations by means of an electrostatic model. Moreover, combining experimental as well as computational results, the exclusive axial orientation of a Cl atom in one of the compounds could be explained by an interplay of kinetic and energetic effects.

Journal Article↗
PubMed2000

Suppression of acute and chronic opioid withdrawal by a selective soluble guanylyl cyclase inhibitor.

Previous studies have shown that activation of N-methyl-D-aspartate (NMDA) receptors and formation of nitric oxide (NO) contributes to the hyperactivity of locus coeruleus (LC) noradrenergic neurons and behavioural symptoms seen during opioid withdrawal. However, the role of soluble guanylyl cyclase (sGC), the 'physiological' target of NO, in this phenomenon is unclear. In this study, the effect of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a highly selective sGC inhibitor, on the naloxone-precipitated morphine withdrawal was examined using differential normal pulse voltammetry (DNPV) to measure LC activity, in vivo microdialysis to measure glutamate/aspartate release response, and behavioural assessment to evaluate withdrawal symptoms. In halothane-anaesthetized rats, acute intracerebroventricular (i.c.v.) morphine (10 microg) reduced the catecholamine oxidation current (CA.OC) (54.5+/-4.9% of baseline). Naloxone (2 mg/kg, i.v.) reversed this action of morphine and produced a rebound increase in CA.OC (136.1+/-6.0% of baseline), representing acute morphine withdrawal. Administration of ODQ (200 nmol, i.c.v.) blocked this response without affecting acute morphine action. In animals chronically treated with morphine (15 microg/microl/h, i.c.v., 5 days), naloxone significantly increased both the CA.OC signal (270.0+/-19.6% of baseline) and the release of L-glu (193+/-30.4%) and L-asp (221.5+/-28.4%) above baseline. These responses were attenuated in animals pretreated with ODQ. In unanaesthetized chronic morphine dependent rats, ODQ treatment suppressed the signs of withdrawal precipitated by naloxone (10 mg/kg). Taken together, the results of this study suggest that sGC plays an intermediary role in the genesis of LC neuronal hyperactivity and behavioural signs of morphine withdrawal.

Analgesics, Opioid↗
PubMed1999

CD4+ CD45RA+ and CD4+ CD45RO+ T cells differ in their TCR-associated signaling responses.

Peripheral CD4+ T cells can be divided into two different functional populations based on the expression of distinct isoforms of the surface molecule CD45. We have investigated the differences in the proximal signaling induced by anti-CD3 monoclonal antibody in purified populations of "naive" CD45RA+ and "memory" CD45RO+ human CD4+ T cells. Expression of cell surface CD3, CD4 and CD28 was comparable between RA+ and RO+ cells. However, TCR-directed stimulation in the form of anti-CD3 produced markedly different patterns of intracellular signaling. Greater inositol triphosphate generation occurred in naive cells and the rise in intracellular free calcium was also substantially greater in naive than in memory cells. Cells with the naive phenotype were considerably more active in TCR-dependent tyrosine phosphorylation, both at an overall level and specifically in terms of TCR-zeta and ZAP-70 phosphorylation. Despite these differences in phosphorylation, the amounts of TCR-zeta, ZAP-70 and Ick were equivalent between the two subsets. These findings suggest that the TCR-dependent signaling is differentially regulated in naive and memory CD4+ T cells. This may be due to differences in the way that the two isoforms of the CD45 phosphatase regulate the activity of proximal kinases in the TCR signaling pathway, and could be an important means by which the unique functions of differentiated T cell populations are maintained.

Animals↗
PubMed1999

Activation of the rostral ventrolateral medulla in an acute anesthetized rodent strychnine model of allodynia.

UNLABELLED: After the administration of intrathecal strychnine, allodynia is manifested as activation of supraspinal sites involved in pain processing and enhancement of cardiovascular responses evoked by normally innocuous stimuli. The objective of this study was to investigate the effect of strychnine-induced allodynia on adrenergic neuronal activity in the C1 area of the rostral ventrolateral medulla (RVLM), a major site involved in cardiovascular regulation. The effect of intrathecal strychnine (40 microg) or saline followed by repeated hair deflection to caudal lumbar dermatomes in the urethane-anesthetized rat was assessed by measuring voltammetric changes in the RVLM catechol oxidation current (CA x OC), mean arterial pressure (MAP), and heart rate (HR). After the administration of intrathecal strychnine, hair deflection evoked a significant and sustained increase in the RVLM CA x OC and MAP (peak 146.4%+/-5.6% and 159%+/-18.4% of baseline, respectively; P < 0.05). There was a nonsignificant increase in HR (peak 128%+/-8.2%). In the absence of hair deflection, there was no demonstrable change. Intrathecal saline-treated rats failed to demonstrate changes in RVLM CA x OC, MAP, or HR. In the present study, we demonstrated that, after the administration of intrathecal strychnine, innocuous hair deflection evokes temporally related neuronal activation in the rat RVLM and an increase in MAP. This suggests that the RVLM mediates, at least in part, the cardiovascular responses during strychnine allodynia. IMPLICATIONS: Neural injury-associated pain, as manifested by allodynia, is resistant to conventional treatment. In a rat model of allodynia, we demonstrated activation of the brain region involved in sympathetic control. Innovative therapies that target this region may be successful in managing this debilitating condition.

Anesthesia↗
PubMed1999

Spinal action of ketorolac, S(+)- and R(-)-ibuprofen on non-noxious activation of the catechol oxidation in the rat locus coeruleus: evidence for a central role of prostaglandins in the strychnine model of allodynia.

BACKGROUND: Blockade of spinal glycine receptors with intrathecal strychnine produces an allodynia-like state in the anesthetized rat. Innocuous hair deflection in the presence of intrathecal strychnine induces a nociceptive-like activation of catechol oxidation in the locus coeruleus and enhances cardiovascular responses. Because prostaglandins play a central role in augmenting pain, this study evaluated the effect of intrathecal nonsteroidal antiinflammatory drugs in strychnine-induced allodynia. METHODS: In urethane-anesthetized rats, changes in catechol oxidation in the locus coeruleus, measured using in vivo voltammetry, and cardiovascular parameters evoked by hair deflection of caudal dermatomes were determined after strychnine (40 microg) or saline were administered intrathecally. Subsequently, the effects of 30 microg ketorolac, 10 microg S(+)-ibuprofen, and 10 microg R(-)-ibuprofen administered intrathecally were evaluated. RESULTS: After strychnine was administered intrathecally, hair deflection evoked an increase in the locus coeruleus catechol oxidation (peak, 149.7+/-7.2% of baseline) and mean arterial blood pressure (peak, 127.5+/-3.8% of baseline). These responses were not observed after saline was administered intrathecally. All hair deflection-evoked, strychnine-dependent peak responses were attenuated significantly with intrathecally administered ketorolac and S(+)-ibuprofen but not with R(-)-ibuprofen. CONCLUSIONS: Locus coeruleus catechol oxidation is a sensitive biochemical index of strychnine-induced allodynia and is correlated temporally with the cardiovascular responses evoked by hair deflection during spinal glycinergic inhibition. The ability of intrathecally administered ketorolac and S(+)-ibuprofen, but not R(-)-ibuprofen, to suppress the locus coeruleus catechol oxidation and cardiovascular peak responses evoked during strychnine-induced allodynia provide evidence that central prostaglandins play an important role in the abnormal sensory processing of strychnine-induced allodynia.

Anesthesia↗
PubMed1998

Surmounting health information network barriers: the greater Dayton area experience.

The greater Dayton area has begun building the nation's first advanced technology community network for sharing patient medical information among independent hospitals. Its success in doing so has resulted from the surmounting of numerous business and technical barriers. Others planning to develop such networks can learn from the Dayton experience.

Community Networks↗
PubMed1996

Phosphorylation of p53 at the casein kinase II site selectively regulates p53-dependent transcriptional repression but not transactivation.

The p53 tumour suppressor protein is a potent transcription factor which plays a central role in the defence of cells against DNA damage and the propagation of malignant clones. We have previously shown that phosphorylation of serine 386 in mouse p53 by the growth- associated protein kinase, casein kinase II (CKII), plays an important role in the ability of p53 to block the proliferation of drug-resistant colonies. In this paper we show that blocking phosphorylation of serine 386 through an alanine substitution, or placing a constitutive negative charge at this position in the form of aspartate, had no significant influence on p53-dependent transcriptional activation of a promoter containing 13 copies of a p53 consensus binding sequence, or of the p21WAF1 promoter which is a natural target for p53. In contrast, the alanine mutant showed a weak reduction in the ability of p53 to repress expression from the c-fos promoter, which is a target for p53-dependent repression in vivo. Strikingly, when the repression of the SV40 early promoter was examined, a reduction in the repression capacity of up to 5-fold was observed. Moreover, repression of the SV40 promoter could be partially restored by aspartic acid substitution at the phosphorylation site. These data indicate that phosphorylation at a specific C-terminal site can selectively regulate p53-dependent repression, but not transactivation.

Animals↗
PubMed1996

Behavioural effects of infectious mononucleosis.

The aim of the present study was to provide preliminary information on the acute and chronic effects of infectious mononucleosis (IM) on memory, attention, psychomotor performance and mood. These issues were examined by comparing individuals with acute IM, those who had the initial illness some months before, and matched healthy controls. Objective measures of memory, attention, motor skills and visual functions were obtained, as were subjective reports of mood. The results showed selective effects of acute IM on performance and mood, with the profile of impairments being very similar to those observed in previous studies of influenza. Different impairments were observed in subjects who had the primary illness several months before, and the effects observed in this group were similar to those observed in recent studies of chronic fatigue syndrome patients. Both acute and chronic IM subjects reported similar levels of symptoms and psychopathology, with both groups having greater scores than the controls. However, the performance impairments did not reflect symptoms or psychopathology. One may conclude that the study of IM will provide important data on both the acute and longer lasting effects of viral infections on the brain and behaviour.

Adult↗
PubMed1995

Therapeutic potentiation of the immune system by costimulatory Schiff-base-forming drugs.

Immune responses are orchestrated by CD4 T lymphocytes, which receive a cognitive signal when clonally distributed receptors are occupied by major histocompatibility complex (MHC) class II-bound peptides on antigen-presenting cells (APCs). The APCs provide costimulatory signals, through macromolecules such as CD80, that regulate outcomes in terms of T-cell activation or anergy. We have studied essential complementary chemical events in the form of Schiff base formation between carbonyls and amines that are constitutively expressed on presenting cell and T-cell surfaces and provide a new target for manipulation of immune responses. Here we show that small Schiff base-forming molecules can substitute for the physiological donor of carbonyl groups and provide a costimulatory signal to CD4 Th-cells through a mechanism that activates clofilium-sensitive K+ and Na+ transport. One such molecule, tucaresol, enhances CD4 Th-cell responses, selectively favouring a Th1-type profile of cytokine production. In vivo tucaresol potently enhances CD4 Th-cell priming and CD8 cytotoxic T-cell priming to viral antigens, and has substantial therapeutic activity in murine models of disease.

Adjuvants, Immunologic↗
PubMed1995

Myocardial ischemia and reperfusion: a murine model.

Myocardial ischemia followed by reperfusion promotes a complex series of inflammatory reactions as noted in a variety of large animal studies. With development of genetically altered mice, there is intense interest in developing murine models to study mechanisms operative in cardiovascular disease. We developed a mouse model to study coronary artery occlusion and reperfusion effects and the method required to perform these studies both acutely and chronically. In mice, we applied a left anterior descending coronary artery occlusion either permanently or for 30 or 60 min followed by reperfusion allowing flow through the previously occluded coronary artery bed. Reperfusion was documented visually as well as by using Doppler ultrasound and histopathological techniques. The area at risk (AAR) and infarct size (IS) were assessed by EVans blue dye and triphenyltetrazolium chloride staining with computerized planimetry using an image analysis software program. The infarct as percentage of AAR and IS as percentage of the left ventricle in 13 mice with permanent occlusion was 68.6 +/- 4.4 and 28.0 +/- 2.8%, respectively. Reperfusion after occlusions of 60 and 30 min resulted in a significant decrease in IS as a percentage of the AAR compared with permanent occlusion. Histological examination of the ischemic and reperfused myocardium shows infiltration of leukocytes into the ischemic region as well as contraction bands classically associated with reperfusion. This new model allows assessment of AAR, IS, cardiac function, and pathophysiology in the mouse. With the current technology to develop genetically altered mice for overexpression or targeted mutations of various genes, this model is used to understand the complex pathophysiology of ischemia and reperfusion injury.

Animals↗
PubMed1995

Early elemental and ionic changes in cultured cells after stimulation with epidermal growth factor.

Stimulation of A431 cells (a human vulval epidermal cell line) with 50 ng/ml of epidermal growth factor (EGF) in the presence of 1.7 mM extracellular calcium produced a sharp and sustained rise in intracellular ionic Ca2+, increased elemental Na, decreased K and a rise in Ca. In the absence of extracellular calcium, the initial Ca2+ rise remained but the sustained elevation of intracellular Ca2+ was abolished, Na and K fluxes were variable and the Ca did not change. Increased Na and decreased K was marked at 2 minutes and returned to the control value after 60 minutes. The increase in Ca was an early event. Cells stimulated with EGF showed a pronounced morphological disruption, especially the mitochondria. The response of NR6/SA3 and NR6/DC7 cells (genetically engineered rodent fibroblast cell lines) to EGF stimulation was higher than that of the A431 cells, as was the resting cytoplasmic Ca2+. Untreated NR6/SA3 and NR6/DC7 cells possessed an increased Na/K ratio when compared with A431 cells.

Animals↗
PubMed1993

Programs for phasing by entropy maximization as implemented in Xtal3.2: a crystallographic software system.

Xtal3.2, a crystallographic software package, is an international development project involving about 40 researchers over a full spectrum of crystallographic interests. This development has been supported by many national and international agencies and commercial institutions since the first version in 1983. The 1992 release, Xtal3.2, contains software for 95 different calculations. These range from the processing of raw diffraction data to interactive molecular graphics, atomic charge estimation, electronic publication preparation, and the structure solution and refinement of small and large molecules. Tests of the Xtal programs for phase determination and phase refinement by the application of 'maximum entropy' are presented.

Journal Article↗