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C Loomis

Publications and source records attributed to C Loomis.

At least 19 recordsLinked to original sources
PubMed2005

Grid-enabling medical image analysis.

Grids have emerged as a promising technology to handle the data and compute intensive requirements of many application areas. Digital medical image processing is a promising application area for grids. Given the volume of data, the sensitivity of medical information, and the joint complexity of medical datasets and computations expected in clinical practice, the challenge is to fill the gap between the grid middleware and the requirements of clinical applications. The research project AGIR (Grid Analysis of Radiological Data) presented in this paper addresses this challenge through a combined approach: on one hand, leveraging the grid middleware through core grid medical services which target the requirements of medical data processing applications; on the other hand, grid-enabling a panel of applications ranging from algorithmic research to clinical applications.

Computer Communication Networks↗
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

Fibroma induction in rat skin following single or multiple doses of 1.0 GeV/nucleon 56Fe ions from the Brookhaven Alternating Gradient Synchrotron (AGS).

Rat skin was exposed to the plateau region of the 1.0 GeV/nucleon 56Fe beam at the Brookhaven AGS. Rats were irradiated or not with single of split doses of 56Fe or argon; some 56Fe-exposed rats were fed 250 ppm retinyl acetate continuously in the lab chow beginning 1 week before irradiation. All lesions were noted, photographed and identified for eventual histological diagnosis. The preponderance of the tumors so far are fibromas. The data show that single doses of 56Fe ions are 2 or 3 fold more effective than argon in producing tumors at 4.5 Gy but are about equally effective at 3.0 Gy and 9.0 Gy. The presence of 250 ppm retinyl acetate in the lab chow reduced the incidence of tumors by about 50-60% in comparison to groups exposed only to the radiation. These are preliminary findings based on only about one-fourth the eventual number of tumors expected.

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↗
PubMed1997

Use of differential normal pulse voltammetry for the measurement of locus coeruleus catecholaminergic metabolism in an acute anaesthetized rodent model of allodynia: effect of mexiletine.

Neuropathic pain can be triggered by non-painful stimuli (e.g., light touch), a sensory abnormality termed allodynia. The acute blockade of spinal glycine receptors with intrathecal strychnine induces a reversible allodynia-like state in the rat. We describe the application of in vivo differential normal pulse voltammetry with carbon fibre micro-electrodes for monitoring the catechol oxidation current (CAOC) of the locus coeruleus (LC) in the strychnine model of allodynia. In addition, we tested the effect of mexiletine, a drug useful in the management of clinical neuropathic pain in this model. Our results show that somatosensory processing in the spinal cord of urethane-anaesthetized rats is radically altered during glycine receptor blockade such that the normally innocuous stimulus of hair deflection causes the marked activation of the LC as determined using in vivo differential normal pulse voltammetry. Mexiletine suppressed the LC and cardiovascular responses of strychnine induced allodynia. Results of this study indicate that LC CAOC, an index of LC neuronal activity: (a) is a sensitive biochemical index of strychnine-allodynia; (b) is temporally correlated with the cardiovascular and motor responses evoked by hair deflection during glycine receptor blockade; and (c) can be used to quantitate allodynia in the strychnine model.

Anesthesia↗
PubMed1996

Effects of sphingosine stereoisomers on P-glycoprotein phosphorylation and vinblastine accumulation in multidrug-resistant MCF-7 cells.

To investigate the role of protein kinase C (PKC) in the regulation of multidrug resistance and P-glycoprotein (P-gp) phosphorylation, the natural isomer of sphingosine (SPH), D-erythro sphingosine (De SPH), and its three unnatural stereoisomers were synthesized. The SPH isomers showed similar potencies as inhibitors of in vitro PKC activity and phorbol binding, with IC50 values of approximately 50 microM in both assays. Treatment of multidrug-resistant MCF-7ADR cells with SPH stereoisomers increased vinblastine (VLB) accumulation up to 6-fold at 50 microM but did not alter VLB accumulation in drug-sensitive MCF-7 wild-type (WT) cells or accumulation of 5-fluorouracil in either cell line. Phorbol dibutyrate treatment of MCF-7ADR cells increased phosphorylation of P-gp, and this increase was inhibited by prior treatment with SPH stereoisomers. Treatment of MCF-7ADR cells with SPH stereoisomers decreased basal phosphorylation of the P-gp, suggesting inhibition of PKC-mediated phosphorylation of P-gp. Most drugs that are known to reverse multidrug resistance, including several PKC inhibitors, have been shown to directly interact with P-gp and inhibit drug binding. SPH stereoisomers did not inhibit specific binding of [3H] VLB to MCF-7ADR cell membranes or [3H]azidopine photoaffinity labeling of P-gp or alter P-gp ATPase activity. These results suggest that SPH isomers are not substrates of P-gp and suggest that modulation of VLB accumulation by SPH stereoisomers is associated with inhibition of PKC-mediated phosphorylation of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Innocuous hair deflection evokes a nociceptive-like activation of catechol oxidation in the rat locus coeruleus following intrathecal strychnine: a biochemical index of allodynia using in vivo voltammetry.

Blockade of spinal glycinergic inhibition with intrathecal (i.t.) strychnine induces a reversible allodynia-like state in both conscious and lightly-anaesthetized rats. Since the locus coeruleus (LC) is activated by noxious stimuli, we determined the effect of non-noxious hair deflection (HD) on noradrenergic neuronal activity in the LC of rats treated with i.t. strychnine. Differential normal pulse voltammetry was used to measure the catechol oxidation current (CA.OC), an index of LC activity. Rats were maintained in a light plane of anaesthesia with i.v. urethane and i.t. strychnine (40 micrograms) was injected near the L1-L2 segment. HD, applied to the caudal dermatomes affected by i.t. strychnine, evoked a significant increase (max. 141 +/- 7%, n = 5, P < 0.05) in CA.OC and mean arterial pressure as compared to baseline (no strychnine). In contrast, HD had no significant effect on CA.OC or mean arterial pressure in the saline-treated rats (n = 5). Pre-treatment with i.t. MK801 (30 micrograms) significantly blocked the increase in CA.OC and mean arterial pressure evoked by HD in strychnine-treated rats. The results of this study indicated that HD, in the presence of i.t. strychnine but not saline, can evoke noradrenergic activity in the LC of lightly anaesthetized rats. This effect on the LC is: (1) comparable to that observed with noxious stimulation without i.t. strychnine; (2) segmentally localized, corresponding to the spinal site of strychnine injection; and (3) mediated by spinal NMDA receptors, consistent with the role of excitatory amino acids in sensory transmission. These data provide the first neurochemical evidence that HD, in the presence of i.t. strychnine, is a nociceptive event, supporting the use of this preparation as an experimental model of allodynia.

Animals↗
PubMed1993

Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets.

Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to contain predominantly PKC alpha, beta I, beta II, and delta with minor immunoreactivity for PKC epsilon, zeta, and eta. In intact platelets, sodium oleate caused a time-dependent redistribution of PKC alpha, beta II, and delta from cytosol to membrane fractions with little effects on PKC beta I. On the other hand, PMA and thrombin induced translocation of all four isoenzymes of PKC. In vitro, oleate partially activated (50% of Vmax) purified calcium-dependent PKC (alpha, beta I, and beta II) with an EC50 of 50 microM whereas it fully activated (100% of Vmax) purified calcium-independent PKC (predominantly delta) with an EC50 of 5 microM. The selective effects of oleate on PKC isoenzymes were investigated in platelet cytosol which contains endogenous PKC and its physiologic substrates. Under these conditions, oleate potently activated calcium-independent PKC causing the phosphorylation of the 40-kDa substrate. Activation of calcium-dependent isoforms occurred only at higher concentrations of oleate. Thus, oleate activates multiple isoenzymes of PKC with predominant effects on calcium-independent PKC.

Amino Acid Sequence↗
PubMed1993

Differential expression of protein kinase C isoenzymes in normal and psoriatic adult human skin: reduced expression of protein kinase C-beta II in psoriasis.

Psoriatic lesions contain elevated levels of 1,2-diacylglycerol, the physiologic activator of protein kinase C (PKC), suggesting that PKC activation may be aberrant in psoriasis. We therefore have investigated the expression and properties of PKC isozymes in normal and psoriatic skin and in human skin cells. Chromatographic and immunoblot analyses revealed the presence of the calcium-dependent PKC isozymes PKC-alpha and -beta, but not -gamma, in normal human epidermis. PKC-beta was more prominent, constituting two thirds of the total calcium-dependent PKC activity. In psoriatic lesions, expression of both PKC-alpha and -beta was decreased, with preferential reduction (80%) of PKC-beta. Northern analysis and semi-quantitative polymerase chain reaction (PCR) indicated no change in the mRNA levels of PKC-alpha and -beta between normal and psoriatic epidermis. In normal epidermis, PKC-alpha was expressed mainly in the lower epidermis, whereas PKC-beta was localized to the upper cell layers, with very intense staining of CD1a+ Langerhans cells. In psoriasis, PKC-alpha staining was present in the lower epidermis, whereas PKC-beta staining was essentially absent, with the exception of some positive inflammatory cells. In addition to PKC-alpha and beta, immunoblot and Northern/PCR analysis revealed expression of four calcium-independent PKC isozymes, delta, epsilon, zeta, and eta, in both normal and psoriatic skin. There were no significant differences in mRNA levels among any of these PKC isozymes, between normal and psoriatic skin. Soluble PKC-zeta protein was modestly increased (twofold) in psoriatic, compared to normal, skin, whereas the levels of PKC-delta, epsilon, and eta were unchanged. Analysis of PKC isozyme expression in the three major cell types of human epidermis revealed that Langerhans cells and keratinocytes were the major sources of PKC-beta and PKC-zeta, respectively. These data demonstrate the diversity of PKC isozyme expression in human skin, and suggest that alterations of PKC-beta and -zeta may participate in the aberrant regulation of growth and differentiation observed in psoriasis.

Adult↗
PubMed1992

Stereoselective effects of central alpha 2-adrenergic agonist medetomidine on in vivo catechol activity in the rat rostral ventrolateral medulla (RVLM).

The stereoselective central effects of a novel, highly potent and selective alpha 2-agonist medetomidine on adrenergic neuronal activity, reflected by changes in catechol oxidation current, in the rostral ventrolateral medulla of the halothane-anesthetized rat were examined using in vivo differential normal pulse voltammetry. Dexmedetomidine, the active isomer, significantly decreased catechol oxidation current to 33.4 +/- 4.5% of baseline when given centrally (1 microgram, i.c.v.) and to 10.3 +/- 3.9% of baseline when given systemically (50 micrograms/kg, i.v.). Dexmedetomidine also significantly reduced mean arterial blood pressure by 19.9% following central administration but significantly increased mean arterial blood pressure by 59.9% following systemic administration. Levomedetomidine, the inactive isomer, had no effect on catechol oxidation current or blood pressure. The depressant effects of dexmedetomidine on catechol oxidation current were reversed by the selective alpha 2-adrenoceptor antagonist atipamezole (2 micrograms, i.c.v. or 200 micrograms/kg, i.v.). The results of the present study demonstrate, to our knowledge, for the first time the central stereoselective effects of medetomidine and antagonism by atipamezole on rostral ventrolateral medulla activity in the anesthetized rat.

Adrenergic alpha-Agonists↗
PubMed1992

Translocation of protein kinase C isozymes in thrombin-stimulated human platelets. Correlation with 1,2-diacylglycerol levels.

Human platelets were found by immunoblot analysis to express protein kinase C (PKC) isozymes alpha, beta, delta, and zeta, but not gamma, epsilon, or eta. Exposure of platelets to thrombin, in the presence of 1 mM calcium, induced increased membrane association of PKC-alpha, -beta, and -zeta, while the subcellular distribution of PKC-delta remained unaltered. Maximal membrane association (2-fold) of PKC-alpha, -beta, and -zeta occurred within 1 min and was sustained for at least 10 min after the addition of thrombin. Similar results were obtained in the presence of the RGDS peptide, which blocks thrombin-induced binding of fibrinogen to its receptor, which indicates that PKC translocation was independent of fibrinogen binding. In the absence of added extracellular calcium, thrombin-induced translocation of PKC-alpha, -beta, and -zeta was transient, reaching a maximum at 1 min and returning to base line by 10 min. In the presence of calcium, thrombin induced a rapid (within 15 s) 8-fold rise in inositol 1,4,5-trisphosphate, which returned to baseline levels within 1 min, and a biphasic increase in sn-1,2-diacylglycerol (DAG), with peaks at 15 s and 2 min, which remained elevated for at least 5 min. Chelation of external calcium abolished the second phase of DAG formation but had no effect on the kinetics or magnitude of the increase in inositol 1,4,5-trisphosphate or the first phase of DAG formation. Two early PKC-dependent functions, serotonin release and 40-kDa protein phosphorylation, were independent of extracellular calcium and sustained DAG. These data demonstrate that in thrombin-stimulated human platelets the duration of the increased PKC membrane association closely parallels that of increased DAG content, and sustained elevations in DAG content and PKC translocation are dependent on extracellular calcium.

Amino Acid Sequence↗