bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Characterization of Novel Organo‐Inorganic Hybrid Material of Poly(3,4‐Ethylene Dioxythiophene) and PhosphomolybdateAnion
Authors: Murugan A. Vadivel , Kwon C.-W. , Campet G. , Kale B. B.
Published: October 2004

The organo‐inorganic hybrid material, consisting of Poly(3,4‐Ethylene Dioxythiophene) (PEDOT) doped with phosphomolybdate cluster anions
, has been synthesized by direct in situ oxidative polymerization
of 3,4‐Ethylene Dioxythiophene (EDOT) with phosphomolybdic acid (H3PMo12O40)
. Its characterization is investigated by Fourier Transform Infrared Spectroscopy (FT‐IR) and Scanning Electron Microscopy (SEM). The hybrid material presents predominantly high electronic conductivities of around 2.0 and 7.0 S cm−1 at 300 and 400K respectively.
Distinct molecular forms of β-catenin are targeted to adhesive or transcriptional complexes
Authors: Gottardi Cara J. , Gumbiner Barry M.
Published: October 2004

β-Catenin plays essential roles in both cell–cell adhesion and Wnt signal transduction, but what precisely controls β-catenin targeting to cadherin adhesive complexes, or T-cell factor (TCF)-transcriptional complexes is less well understood. We show that during Wnt signaling, a form of β-catenin is generated that binds TCF but not the cadherin cytoplasmic domain. The Wnt-stimulated, TCF-selective form is monomeric and is regulated by the COOH terminus of β-catenin, which selectively competes cadherin binding through an intramolecular fold-back mechanism. Phosphorylation of the cadherin reverses the TCF binding selectivity, suggesting another potential layer of regulation. In contrast, the main cadherin-binding form of β-catenin is a β-catenin–α-catenin dimer, indicating that there is a distinct molecular form of β-catenin that can interact with both the cadherin and α-catenin. We propose that participation of β-catenin in adhesion or Wnt signaling is dictated by the regulation of distinct molecular forms of β-catenin with different binding properties, rather than simple competition between cadherins and TCFs for a single constitutive form. This model explains how cells can control whether β-catenin is used independently in cell adhesion and nuclear signaling, or competitively so that the two processes are coordinated and interrelated.
The forces that position a mitotic spindle asymmetrically are tethered until after the time of spindle assembly
Authors: Labbé Jean-Claude , McCarthy Erin K. , Goldstein Bob
Published: October 2004

Regulation of the mitotic spindle's position is important for cells to divide asymmetrically. Here, we use Caenorhabditis elegans embryos to provide the first analysis of the temporal regulation of forces that asymmetrically position a mitotic spindle. We find that asymmetric pulling forces, regulated by cortical PAR proteins, begin to act as early as prophase and prometaphase, even before the spindle forms and shifts to a posterior position. The spindle does not shift asymmetrically during these early phases due to a tethering force, mediated by astral microtubules that reach the anterior cell cortex. We show that this tether is normally released after spindle assembly and independently of anaphase entry. Monitoring microtubule dynamics by photobleaching segments of microtubules during anaphase revealed that spindle microtubules do not undergo significant poleward flux in C. elegans. Together with the known absence of anaphase A, these data suggest that the major forces contributing to chromosome separation during anaphase originate outside the spindle. We propose that the forces positioning the mitotic spindle asymmetrically are tethered until after the time of spindle assembly and that these same forces are used later to drive chromosome segregation at anaphase.
Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis
Authors: Pece Salvatore , Serresi Michela , Santolini Elisa , Capra Maria , Hulleman Esther , Galimberti Viviana , Zurrida Stefano , Maisonneuve Patrick , Viale Giuseppe , Di Fiore Pier Paolo
Published: October 2004

The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis.
Remodeling of Axonal Connections Contributes to Recovery in an Animal Model of Multiple Sclerosis
Authors: Kerschensteiner Martin , Bareyre Florence M. , Buddeberg Bigna S. , Merkler Doron , Stadelmann Christine , Brück Wolfgang , Misgeld Thomas , Schwab Martin E.
Published: October 2004

In multiple sclerosis (MS), inflammation in the central nervous system (CNS) leads to damage of axons and myelin. Early during the clinical course, patients can compensate this damage, but little is known about the changes that underlie this improvement of neurological function. To study axonal changes that may contribute to recovery, we made use of an animal model of MS, which allows us to target inflammatory lesions to the corticospinal tract (CST), a major descending motor pathway. We demonstrate that axons remodel at multiple levels in response to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, local interneurons show regenerative sprouting; (b) above the lesion, descending CST axons extend new collaterals that establish a “detour” circuit to the lumbar target area, whereas below the lesion, spared CST axons increase their terminal branching; and (c) in the motor cortex, the distribution of projection neurons is remodeled, and new neurons are recruited to the cortical motor pool. Behavioral tests directly show the importance of these changes for recovery. This paper provides evidence for a highly plastic response of the motor system to a single neuroinflammatory lesion. This framework will help to understand the endogenous repair capacity of the CNS and to develop therapeutic strategies to support it.
CTLA-4–Ig Activates Forkhead Transcription Factors and Protects Dendritic Cells from Oxidative Stress in Nonobese Diabetic Mice
Authors: Fallarino Francesca , Bianchi Roberta , Orabona Ciriana , Vacca Carmine , Belladonna Maria L. , Fioretti Maria C. , Serreze David V. , Grohmann Ursula , Puccetti Paolo
Published: October 2004

Prediabetes and diabetes in nonobese diabetic (NOD) mice have been targeted by a variety of immunotherapies, including the use of a soluble form of cytotoxic T lymphocyte antigen 4 (CTLA-4) and interferon (IFN)-γ. The cytokine, however, fails to activate tolerogenic properties in dendritic cells (DCs) from highly susceptible female mice early in prediabetes. The defect is characterized by impaired induction of immunosuppressive tryptophan catabolism, is related to transient blockade of the signal transducer and activator of transcription (STAT)1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. Here, we show that soluble CTLA-4 imparts suppressive properties to DCs from early prediabetic NOD female mice through mechanisms that rely on autocrine signaling by IFN-γ. Although phosphorylation of STAT1 in response to IFN-γ is compromised in those mice, CTLA-4 obviates the defect. IFN-γ–driven expression of tryptophan catabolism by CTLA-4–immunoglobulin is made possible through the concomitant activation of the Forkhead Box class O (FOXO) transcription factor FOXO3a, induction of the superoxide dismutase gene, and prevention of peroxynitrite formation.
Plasma Cell Ontogeny Defined by Quantitative Changes in Blimp-1 Expression
Authors: Kallies Axel , Hasbold Jhagvaral , Tarlinton David M. , Dietrich Wendy , Corcoran Lynn M. , Hodgkin Philip D. , Nutt Stephen L.
Published: October 2004

Plasma cells comprise a population of terminally differentiated B cells that are dependent on the transcriptional regulator B lymphocyte–induced maturation protein 1 (Blimp-1) for their development. We have introduced a gfp reporter into the Blimp-1 locus and shown that heterozygous mice express the green fluorescent protein in all antibody-secreting cells (ASCs) in vivo and in vitro. In vitro, these cells display considerable heterogeneity in surface phenotype, immunoglobulin secretion rate, and Blimp-1 expression levels. Importantly, analysis of in vivo ASCs induced by immunization reveals a developmental pathway in which increasing levels of Blimp-1 expression define developmental stages of plasma cell differentiation that have many phenotypic and molecular correlates. Thus, maturation from transient plasmablast to long-lived ASCs in bone marrow is predicated on quantitative increases in Blimp-1 expression.
Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation
Authors: Gallegos Alena M. , Bevan Michael J.
Published: October 2004

Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We show that professional BM-derived APCs acquire TSAs from Mtecs and delete autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs did not delete the CD4 T cell population tested in this study, Mtec presentation efficiently deleted both monoclonal and polyclonal populations of CD8 T cells. For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage, presumably as the cells transit from the cortex to the medulla. These studies reveal a cooperative relationship between Mtecs and BM-derived cells in thymic elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a subset of autoreactive T cells, BM-derived cells extend the range of clonal deletion by cross-presenting antigen captured from Mtecs.
Dexmedetomidine Pharmacodynamics: Part II
Authors: Cortinez Luis I. , Hsu Yung-Wei , Sum-Ping Sam T. , Young Christopher , Keifer John C. , MacLeod David , Robertson Kerri M. , Wright David R. , Moretti Eugene W. , Somma Jacques
Published: October 2004

Background

Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans.

Methods

This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41 degrees to 50 degrees C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model.

Results

Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1 degrees C at baseline to 48.4 degrees and 49.1 degrees C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients gamma during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2 degrees C) and a decrease in the steepness of the curve (decreased gamma from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and gamma).

Conclusion

As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.
Impact of Bispectral Index Monitoring on Stress Response and Propofol Consumption in Patients Undergoing Coronary Artery Bypass Surgery
Authors: Bauer Michael , Wilhelm Wolfram , Kraemer Thomas , Kreuer Sascha , Brandt Andreas , Adams Hans Anton , Hoff Gudrun , Larsen Reinhard
Published: October 2004

Background

Bispectral Index (BIS)-titrated administration allows a reduction of propofol infusion rates in patients undergoing surgery. Resulting differences in anesthetic depth might affect the stress response to surgery involving neural circuitry not reflected in the electroencephalogram.

Methods

Forty patients scheduled to undergo elective coronary artery bypass grafting receiving a background infusion of remifentanil (0.3 microg . kg . min) were anesthetized with intravenous propofol delivered by target-controlled infusion according to the Marsh pharmacokinetic model under BIS monitoring. In a randomized, prospective design, 20 patients received propofol at a target concentration of 3 microg/ml, whereas in 20 patients propofol was titrated to maintain a BIS value of 40-50. Plasma concentrations of propofol (by means of gas chromatography-mass spectrometry), epinephrine, norepinephrine (by means of high-pressure liquid chromatography), cortisol (by means of radioimmunoassay), and interleukins 6 and 10 (by means of enzyme-linked immunosorbent assay) were measured repeatedly throughout surgery.

Results

BIS monitoring allowed a 30% reduction of propofol infusion rates and a similar decrease in plasma propofol concentrations in the BIS group without affecting the stress response to surgery for the group mean. None of the patients reported awareness during a standardized interview. Interestingly, propofol-remifentanil anesthesia blunted the release of epinephrine and cortisol to bypass surgery completely even when the propofol infusion rate was reduced according to BIS values.

Conclusions

Total intravenous anesthesia using propofol-remifentanil effectively attenuates the neurohumoral stress response to coronary bypass surgery involving cardiopulmonary bypass. Titration of propofol using BIS allows for significant reduction of propofol consumption, with only minor effects on stress response under these conditions.
Narcotrend® Does Not Adequately Detect the Transition between Awareness and Unconsciousness in Surgical Patients
Authors: Schneider Gerhard , Kochs Eberhard F. , Horn Bettina , Kreuzer Matthias , Ningler Michael
Published: October 2004

Background

The Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany) is a dimensionless number between 0 and 100 that is calculated from the electroencephalogram and inversely correlates with depth of hypnosis. The current study evaluates the capability of the Narcotrend to separate awareness from unconsciousness at the transition between these levels.

Methods

Electroencephalographic recordings of 40 unpremedicated patients undergoing elective surgery were analyzed. Patients were randomly assigned to receive (1) sevoflurane-remifentanil (</= 0.1 microg . kg . min), (2) sevoflurane-remifentanil (>/= 0.2 microg . kg . min), (3) propofol-remifentanil (</= 0.1 microg . kg . min), or (4) propofol-remifentanil (>/= 0.2 microg . kg . min). Remifentanil and sevoflurane or propofol were given until loss of consciousness. After tracheal intubation, propofol or sevoflurane was stopped until return of consciousness and then restarted to induce loss of consciousness. After surgery, drugs were discontinued. Narcotrend values at loss and return of consciousness were compared with each other, and anesthetic groups were compared. Prediction probability was calculated from values at the last command before and at loss and return of consciousness.

Results

At 105 of 316 analyzed time points, the Narcotrend did not calculate an index, and the closest calculated value was analyzed. No significant differences between loss and return of consciousness were found. In group 1, Narcotrend values were significantly higher than in group 3. Prediction probability was 0.501.

Conclusions

In these challenging data, the Narcotrend did not differentiate between awareness and unconsciousness. In addition, Narcotrend values were not independent from the anesthetic regimen.
Induction Speed Is Not a Determinant of Propofol Pharmacodynamics
Authors: Doufas Anthony G. , Bakhshandeh Maryam , Bjorksten Andrew R. , Shafer Steven L. , Sessler Daniel I.
Published: October 2004

Background

Evidence suggests that the rate at which intravenous anesthetics are infused may influence their plasma-effect site equilibration. The authors used five different rates of propofol administration to test the hypothesis that different sedation endpoints occur at the same effect site propofol concentration, independent of the infusion rate. The authors concurrently evaluated the automated responsiveness monitor (ARM) against other sedation measures and the propofol effect site concentration.

Methods

With Human Studies Committee approval, 18 healthy volunteers received five consecutive target-controlled propofol infusions. During each infusion, the effect site concentration was increased by a rate of 0.1, 0.3, 0.5, 0.7, or 0.9 microg . ml . min. The Bispectral Index and ARM were recorded at frequent intervals. The times of syringe drop and loss and recovery of responsiveness were noted. Pharmacokinetic and pharmacodynamic modeling was performed using NONMEM.

Results

When the correct rate of plasma-effect site equilibration was determined for each individual (plasma-effect site equilibration = 0.17 min, time to peak effect = 2.7 min), the effect site concentrations associated with each clinical measure were not affected by the rate of increase of effect site propofol concentration. ARM correlated with all clinical measures of drug effect. Subjects invariably stopped responding to ARM at lower effect site propofol concentrations than those associated with loss of responsiveness.

Conclusions

: Population-based pharmacokinetics, combined with real-time electroencephalographic measures of drug effect, may provide a means to individualize pharmacodynamic modeling during target-controlled drug delivery. ARM seems useful as an automated measure of sedation and may provide the basis for automated monitoring and titration of sedation for a propofol delivery system.
Effects of Different Catecholamines on the Dynamics of Volume Expansion of Crystalloid Infusion
Authors: Vane Luiz A. , Prough Donald S. , Kinsky Michael A. , Williams Chad A. , Grady James J. , Kramer George C.
Published: October 2004

Background

The authors studied the influence of alpha, beta, and dopaminergic catecholamines on blood volume expansion in conscious normovolemic sheep before, during, and after a bolus infusion of a crystalloid.

Methods

A 0.9% NaCl bolus (24 ml/kg in 20 min) was infused in four paired experiments each: no drug, dopamine infusion (50 microg . kg . min), isoproterenol infusion (0.1 microg . kg . min), and phenylephrine infusion (3 microg . kg . min). Blood volume expansion was calculated by the dilution of blood hemoglobin concentration.

Results

Dopamine had little effect on peak blood volume expansion (12.7 +/- 0.9 ml/kg) compared with 0.9% NaCl (13.0 +/- 2.7 ml/kg); in contrast, isoproterenol augmented blood volume expansion (18.5 +/- 1.8 ml/kg), and phenylephrine reduced blood volume expansion (8.9 +/- 1.4 ml/kg). Two hours after the 0.9% NaCl bolus, sustained blood volume expansion was greatest in the isoproterenol protocol (12.2 ml/kg), whereas the dopamine protocol (6.8 ml/kg) remained similar to the control protocol (4.1 ml/kg), and the phenylephrine protocol had a net volume loss (-1.9 ml/kg). Some blood volume expansion differences were attributed to changes in renal function as phenylephrine infusion increased urinary output, whereas isoproterenol was associated with antidiuresis. However, dopamine caused diuresis and sustained augmentation of blood volume.

Conclusion

Catecholamines can alter the intravascular volume expansion of fluid therapy. beta-Receptor (isoproterenol) stimulation augmented blood volume expansion, whereas alpha (phenylephrine) stimulation reduced blood volume expansion. Combined dopaminergic, beta, and possibly alpha stimulation with dopamine augmented blood volume expansion and cardiac output while inducing diuresis.
Interaction of Halogenated Anesthetics with α- and β-Adrenoceptor Stimulations in Diabetic Rat Myocardium
Authors: Amour Julien , David Jean-Stéphane , Vivien Benoît , Coriat Pierre , Riou Bruno
Published: October 2004

Background

Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown.

Methods

Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD.

Results

Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane.

Conclusion

Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.
Activation of A3Adenosine Receptors Attenuates Lung Injury after In Vivo Reperfusion
Authors: Rivo Julia , Zeira Evelyne , Galun Eithan , Matot Idit
Published: October 2004

Background

A3 adenosine receptor (AR) activation worsens or protects against renal and cardiac ischemia-reperfusion (IR) injury, respectively. The aims of the current study were to examine in an in vivo model the effect of A3AR activation on IR lung injury and investigate the mechanism by which it exerts its effect.

Methods

The arterial branch of the left lower lung lobe in intact-chest, spontaneously breathing cats was occluded for 2 h and reperfused for 3 h (IR group). Animals were treated with the selective A3 receptor agonist IB-MECA (300 microg/kg intravenously) given 15 min before ischemia or with IB-MECA as described, with pretreatment 15 min earlier with the selective A3AR antagonist MRS-1191, the nonsulfonylurea adenosine triphosphate-sensitive potassium channel-blocking agent U-37883A, or the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester.

Results

IB-MECA markedly (P < 0.01) reduced the percentage of injured alveoli (IR, 48 +/- 4%; IB-MECA, 18 +/- 2%), wet:dry weight ratio (IR, 8.2 +/- 0.4; IB-MECA, 4 +/- 2), and myeloperoxidase activity (IR, 0.52 +/- 0.06 U/g; IB-MECA, 0.17 +/- 0.04 U/g). This protective effect was completely blocked by pretreatment with the selective A3AR antagonist MRS-1191 and the adenosine triphosphate-sensitive potassium channel blocking agent U-37883A but not the nitric oxide synthase inhibitor N-nitro-l-arginine benzyl ester.

Conclusions

In the feline lung, the A3AR agonist IB-MECA confers a powerful protection against IR lung injury. This effect is mediated by a nitric oxide synthase-independent pathway and involves opening of adenosine triphosphate-sensitive potassium channels. Therefore, selective activation of A3AR may be an effective means of protecting the reperfused lung.
Selective Postsynaptic Inhibition of Tonic-firing Neurons in Substantia Gelatinosa by μ-Opioid Agonist
Authors: Santos Sónia F. A. , Melnick Igor V. , Safronov Boris V.
Published: October 2004

Background

Spinal substantia gelatinosa (SG) is a site of action of administered and endogenous opioid agonists and is an important element in the system of antinociception. However, little is known about the types of neurons serving as specific postsynaptic targets for opioid action within the SG. To study the spinal mechanisms of opioidergic analgesia, the authors compared the action of mu-opioid agonist [D-Ala, N-Me-Phe, Gly-ol]-enkephalin (DAMGO) on SG neurons with different intrinsic firing properties.

Methods

Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the sensitivity of SG neurons to DAMGO.

Results

Three groups of neurons with distinct distributions in SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1 microm concentration selectively hyperpolarized all tonic-firing neurons tested, whereas none of the adapting- or delayed-firing neurons were affected. The effect of DAMGO on tonic-firing neurons was due to activation of G protein-coupled inward-rectifier K conductance, which could be blocked by 500 microm Ba and 500 microm Cs but increased by 50 microm baclofen. As a functional consequence of DAMGO action, a majority of tonic-firing neurons changed their pattern of intrinsic firing from tonic to adapting.

Conclusions

It is suggested that tonic-firing neurons, presumably functioning as excitatory interneurons, are primary postsynaptic targets for administered and endogenous opioid agonists in spinal SG. Functional transition of cells in this group from tonic to adapting firing mode may represent an important mechanism facilitating opioidergic analgesia.
Mitochondrial Injury and Caspase Activation by the Local Anesthetic Lidocaine
Authors: Johnson Michael E. , Uhl Cindy B. , Spittler Karl-Heinz , Wang Hongxun , Gores Gregory J.
Published: October 2004

Background

Lidocaine, a local anesthetic, can be neurotoxic. However, the cellular mechanisms of its neurotoxicity at concentrations encountered during spinal anesthesia remain unclear.

Methods

The authors examined the mechanisms of lidocaine neurotoxicity in the ND7 cell line derived from rat dorsal root ganglion. Individual neurons were assayed by flow cytometry or microscopy using fluorescent probes of plasma membrane integrity, mitochondrial membrane potential, caspase activity, phospholipid membrane asymmetry, and mitochondrial cytochrome c release.

Results

In the ND7 cell line, lidocaine at 185 mm x 10 min to 2.3 mm x 24 h caused necrosis or late apoptosis. Equimolar Tris buffer and equipotent tetrodotoxin controls were not toxic, indicating that neither osmotic nor Na-blocking effects explain lidocaine neurotoxicity. The earliest manifestation of lidocaine neurotoxicity was complete loss of mitochondrial membrane potential within 5 min after exposure to lidocaine at a concentration of 19 mm or greater. Consistent with these data, 37 mm lidocaine (1%) induced release of mitochondrial cytochrome c into the cytoplasm, as well as plasma membrane blebbing, loss of phosphatidylserine membrane asymmetry, and caspase activation, with release of mitochondrial cytochrome c to the cytoplasm within 2 h. Treatment with z-VAD-fmk, a specific inhibitor of caspases, prevented caspase activation and delayed but did not prevent neuronal death, but did not inhibit the other indicators of apoptosis.

Conclusions

Collectively, these data indicate that lidocaine neurotoxicity involves mitochondrial dysfunction with activation of apoptotic pathways.
Ultrasound-guided Lumbar Facet Nerve Block
Authors: Greher Manfred , Kirchmair Lukas , Enna Birgit , Kovacs Peter , Gustorff Burkhard , Kapral Stephan , Moriggl Bernhard
Published: October 2004

Background

Lumbar facet nerve (medial branch) blocks are often used to diagnose facet joint-mediated pain. The authors recently described a new ultrasound-guided methodology. The current study determines its accuracy using computed tomography scan controls.

Methods

Fifty bilateral ultrasound-guided approaches to the lumbar facet nerves were performed in five embalmed cadavers. The target point was the groove at the cephalad margin of the transverse (or costal) process L1-L5 (medial branch T12-L4) adjacent to the superior articular process. Axial transverse computed tomography scans, with and without 1 ml contrast dye, followed to evaluate needle positions and spread of contrast medium.

Results

Forty-five of 50 needle tips were located at the exact target point. The remaining 5 were within 5 mm of the target. In 47 of 50 cases, the applied contrast dye reached the groove where the nerve is located, corresponding to a simulated block success rate of 94% (95% confidence interval, 84-98%). Seven of 50 cases showed paraforaminal spread, 5 of 50 showed epidural spread, and 2 of 50 showed intravascular spread. Despite the aberrant distribution, all of these approaches were successful, as indicated by contrast dye at the target point. Abnormal contrast spread was equally distributed among all lumbar levels. Contrast traces along the needle channels were frequently observed.

Conclusions

: The computed tomography scans confirm that our ultrasound technique for lumbar facet nerve block is highly accurate for the target at all five lumbar transverse processes (medial branches T12-L4). Aberrant contrast medium spread is comparable to that of the classic fluoroscopy-guided method.
Simultaneous Measurement and Integrated Analysis of Analgesia and Respiration after an Intravenous Morphine Infusion
Authors: Dahan Albert , Romberg Raymonda , Teppema Luc , Sarton Elise , Bijl Hans , Olofsen Erik
Published: October 2004

Background

To study the influence of morphine on chemical control of breathing relative to the analgesic properties of morphine, the authors quantified morphine-induced analgesia and respiratory depression in a single group of healthy volunteers. Both respiratory and pain measurements were performed over single 24-h time spans.

Methods

Eight subjects (four men, four women) received a 90-s intravenous morphine infusion; eight others (four men, four women) received a 90-s placebo infusion. At regular time intervals, respiratory variables (breathing at a fixed end-tidal partial pressure of carbon dioxide of 50 mmHg and the isocapnic acute hypoxic response), pain tolerance (derived from a transcutaneous electrical acute pain model), and arterial blood samples were obtained. Data acquisition continued for 24 h. Population pharmacokinetic (sigmoid Emax)-pharmacodynamic models were applied to the respiratory and pain data. The models are characterized by potency parameters, shape parameters (gamma), and blood-effect site equilibration half-lives. All collected data were analyzed simultaneously using the statistical program NONMEM.

Results

Placebo had no systematic effect on analgesic or respiratory variables. Morphine potency parameter and blood-effect site equilibration half-life did not differ significantly among the three measured effect parameters (P > 0.01). The integrated NONMEM analysis yielded a potency parameter of 32 +/- 1.4 nm (typical value +/- SE) and a blood-effect site equilibration half-life of 4.4 +/- 0.3 h. Parameter gamma was 1 for hypercapnic and hypoxic breathing but 2.4 +/- 0.7 for analgesia (P < 0.01).

Conclusions

Our data indicate that systems involved in morphine-induced analgesia and respiratory depression share important pharmacodynamic characteristics. This suggests similarities in central mu-opioid analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and G proteins). The clinical implication of this study is that after morphine administration, despite lack of good pain relief, moderate to severe respiratory depression remains possible.
Introduction of Anesthesia Resident Trainees to the Operating Room Does Not Lead to Changes in Anesthesia-controlled Times for Efficiency Measures
Authors: Eappen Sunil , Flanagan Hugh , Bhattacharyya Neil
Published: October 2004

Background

Operating room efficiency is an important concern in most hospitals today. Little work has been reported to evaluate the contribution of anesthesia residents to changes in anesthesia-controlled time-related efficiencies in the operating room. The goal of this study was to measure the impact of the initiation of new residents to the operating room on anesthesia-related time measures of operating room efficiency.

Methods

Using the computerized operating room information systems, specific data regarding anesthesia-controlled times were extracted over three distinct 2-week periods over the course of 1 academic year. These included the first 2 weeks of July, when most of the operating rooms were staffed by attending physicians working alone; 2 weeks in September when new anesthesia residents were working in a 2:1 ratio with staff; and 2 weeks in May. The induction times, emergence times, and room turnover times were compared over these three periods for first-year anesthesia residents. Standard descriptive statistics were computed. Analysis of variance testing was then conducted comparing each of these time periods. Significance was set at P < 0.05.

Results

A total of 3,004 surgical procedures were performed during the 2-week study periods in July, September, and May, respectively. For the July, September, and May groups, the mean anesthesia induction times were 17.3, 19.0, and 20.8 min (P = 0.047); the emergence times were 8.7, 9.7, and 10.0 min, (P = 0.024); and the corresponding mean room turnover times were 47.6, 48.5, and 48.6 min (P = 0.907), respectively.

Conclusion

Although statistically significant time differences were found, these data strongly suggest that the initiation of anesthesia trainees to the operating room has no clinically or economically meaningful adverse effect on the anesthesia-controlled time component of operating room efficiency.
Distillation of secret key and entanglement from quantum states
Authors: Devetak Igor , Winter Andreas
Published: October 2004

We study and solve the problem of distilling a secret key from quantum states representing correlation between two parties (Alice and Bob) and an eavesdropper (Eve) via one–way public discussion: we prove a coding theorem to achieve the ‘wire–tapper’ bound, the difference of the mutual information Alice–Bob and that of Alice–Eve, for so–called classical–quantum–quantum–correlations, via one–way public communication. This result yields information–theoretic formulae for the distillable secret key, giving ‘ultimate’ key rate bounds if Eve is assumed to possess a purification of Alice and Bob's joint state. Specializing our protocol somewhat and making it coherent leads us to a protocol of entanglement distillation via one–way LOCC (local operations and classical communication) which is asymptotically optimal: in fact we prove the so–called ‘hashing inequality’, which says that the coherent information (i.e. the negative conditional von Neumann entropy) is an achievable Einstein–Podolsky–Rosen rate. This result is known to imply a whole set of distillation and capacity formulae, which we briefly review.
CHEMICAL COMPOSITION AND PHOTOSYNTHETIC CHARACTERISTICS OF ETHMODISCUS REX (BACILLARIOPHYCEAE): EVIDENCE FOR VERTICAL MIGRATION1
Authors: Villareal Tracy A. , Carpenter Edward J.
Published: October 2004

Ethmodiscus rex (Rattray) Wiseman and Hendey cells from near surface net tows in the Southwest Atlantic Ocean and Caribbean Sea were examined for chemical composition, internal nutrient pool concentrations, and oxygen evolution characteristics. Elemental ratios indicated nitrogen limitation with C:N:P ratios of 125:9:1 (atoms), and carbon: chlorophyll (chl) ratios of 129:1 (weight). However, internal nitrate pools (1.4–27.1 mM) suggested that cells were not N‐limited. Intracellular NO3− accounted for up to 54% (range = 3–54%) of the total N quota in some samples. Photosynthetic parameters were consistent with a high‐light‐adapted population and suggested an instantaneous maximum chl‐specific photosynthetic rate (PBmax) of 4.8–12.4 nmol O2·μg chl−1· h−1. Respiration rates varied ten‐fold and were inversely related to PBmax Ethmodiscus chemical composition and buoyancy characteristics are similar to vertically migrating Rhizosolenia mats and the non‐motile dinoflagellate Pyrocystis noctiluca Murray (Schuett). The presence of internal NO3− pools in Ethmodiscus suggests that this genus is also vertically migrating to exploit sub‐surface nitrogen pools. Such behavior may be widespread in large, non‐motile oceanic phytoplankton. Based on ascent rate data, chemical composition, and photosynthetic rates, we estimate that the entire division–migration cycle for Ethmodiscus requires at least 7–12 days.
THE ACCLIMATED RESPONSE OF GROWTH, PHOTOSYNTHESIS, COMPOSITION, AND CARBON BALANCE TO TEMPERATURE IN THE PSYCHROPHILIC ICE DIATOM NITZSCHIA SERIATA1
Authors: Smith Ralph E. H. , Stapleford Lynn C. , Ridings Richard S.
Published: October 2004

Nitzschia seriata Cleve, a common member of marine bottom ice communities in the Arctic, was grown in unialgal batch cultures to test for compensatory mechanisms for the low temperatures (−1.8° C) typical of its natural habitat. The upper lethal limit for growth was between 12° and 15°C, and the optimum was between 6° and 12° C. The Arrhenius function adequately (R2= 73%) fitted the relationship between growth rate and temperature from – 1.6° up to 10° C, with an average Q10 of 1.9 over the entire range. Light‐saturated and light‐limited rates of photosynthesis (normalized to chlorophyll a or cell carbon) showed complete compensation from 12° to 4° C. Photosynthetic rates, especially at light saturation, declined rapidly at temperatures below 4° C. Susceptibility to photoinhibition was greatest at the lowest growth temperatures. Cellular composition (chlorophyll a, protein, polysaccharide, and lipid contents) was not systematically related to temperature in any simple way, although cell size (carbon per cell) was maximal at the lowest growth temperature. Dark respiration was unmeasurably low (<0.015 day−1) at all growth temperatures. The strategy of adaptation in N. seriata may be characterized as optimizing efficiency and compensation, rather than maximization, of growth rate.
RESPONSE OF CATALASE ACTIVITY TO ENVIRONMENTAL STRESS IN THE FRESHWATER DINOFLAGELLATE PERIDINIUM GATUNENSE1
Authors: Butow Barbara , Wynne David , Tel‐Or Elisha
Published: October 2004

Catalase activity increased in Peridinium gatunense (formerly P. cinctum fa. westii) cells during the decline of the seasonal spring bloom period in Lake Kinneret. This was correlated with the low ambient total CO2 concentration. The relationship was confirmed in laboratory experiments where maximum catalase activity occurred under an atmosphere composed of 30% O2 and 0.003% CO2. Conversely, high CO2 concentrations inhibited catalase activity. The rise in catalase activity was not directly due to increasing environmental pH, as in vitro and in vivo measurements showed a characteristic broad pH curve with a constant activity from pH 6–10 for catalase.

Photoinhibition of catalase occurred above 250 μmol photons · m−2· s−1. However, at high photoinactivating irradiances, photoinhibition was ameliorated under high pO2/pCO2. Such conditions prevail in the Kinneret at the end of the spring. We propose that the enhancement of photorespiration (under high pO2/pCO2) induces a temporary burst in catalase activity despite the progressively photoinhibitory conditions of early summer.
CHLOROPLAST MICROTUBULES IN OEDOGONIUM CAPILLIFORME (CHLOROPHYTA)1
Authors: Ueda Katsumi , Kawaguchi Tomoko , Noguchi Tetsuko
Published: October 2004

Microtubular elements in the chloroplasts (chl‐MTs) of Oedogonium capilliforme Wittrock were examined by conventional electron microscopy and immunoelectron microscopy. Chl‐MTs were frequently seen in the terminal, convex, and concave peripheral regions of the chloroplasts. Each bundle of chl‐MTs was composed of 2–25 tubular elements. Some chl‐MTs were located in the stroma. Chl‐MTs frequently bridged two areas of the envelope membrane near the apex of convex regions of chloroplasts. Some chl‐MTs were closely associated with the envelope membrane via apparent anchors along their length. The distribution patterns of chl‐MTs and their appearance suggest that chl‐MTs are involved in the maintenance of the outer shape of chloroplasts. However, immunoelectron microscopy with an antibody against α‐tubulin indicated that the chl‐MTs are not composed of tubulin.
ATTACHMENT AND FUSION OF GAMETES DURING FERTILIZATION OF PALMARIA SP. (RHODOPHYTA)1
Authors: Mine Ichiro , Tatewaki Masakazu
Published: October 2004

Fertilization of cultured microscopic female gametophytes by spermatia from field‐collected male gametophytes of Palmaria sp. was observed by light and transmission electron microscopy. Liberated spermatia had a prophase‐arrested nucleus with a pair of polar rings. The protoplast of spermatia was covered with ca. a 3‐μm‐thick hyaline covering. After spermatium inoculation, the spermatial covering was attached specifically to the coat surrounding the cell wall of the trichogyne. The spermatial covering was eliminated only at the site of gamete attachment, resulting in direct attachment of the spermatial plasma membrane to the trichogyne within 5 min after spermatium inoculation. This direct attachment was followed by completion of spermatial nuclear division and cell wall formation. The polar rings disappeared before prometaphase. The cytoplasm of the binucleate spermatium invaded the trichogyne cell wall and subsequently fused with the trichogyne cytoplasm. The trichogyne could fuse with many spermatia, and many male nuclei (the derivative nuclei of spermatial nuclear division) could enter the trichogyne cytoplasm.
APPLICATION OF RAPD MARKERS IN AN EXAMINATION OF HETEROSIS IN GELIDIUM VAGUM (RHODOPHYTA)1
Authors: Patwary Mohsin U. , van der Meer John P.
Published: October 2004

Four morphologically indistinguishable isolates of monoecious Gelidium vagum Okamura were crossed reciprocally to obtain hybrids for a study on heterosis in this alga. Approximately 50% outcrossing was achieved by adding a small fragment of the designated female parent to a much larger quantity of designated male thallus in the crossing dish. Hybrids in the mixed population of isomorphic hybrid and inbred sporelings were identified by the presence of male‐specific random amplified polymorphic DNA markers. Growth performance of hybrid tetrasporophytes was compared to that of their gametophytic parents and with inbred tetrasporophytes at near‐optimum and sub‐optimum temperature and density. In general, the hybrids showed growth superiority over inbred lines, particularly under sub‐optimum conditions. In these experiments, the hybrid plants from cross 129 × 130 exhibited a 9.5–130% higher growth rate as compared to the mid‐value of the related inbred tetrasporophytes, strongly suggesting the presence of heterosis.
TWO SOLIERIACEAN ALGAE NEW TO THE MEDITERRANEAN: AGARDHIELLA SUBULATA AND SOLIERIA FILIFORMIS (RHODOPHYTA, GIGARTINALES)1
Authors: Perrone Cesira , Cecere Ester
Published: October 2004

Two Atlantic species found in the Mediterranean Sea were ascribed to the family Solieriaceae on the basis of morphological features. In the extensive drifting beds of the Mar Piccolo basin (Taranto, Ionian Sea), Agardhiella subulata (C. Agardh) Kraft et Wynne and Solieria filiformis (Kützing) Gabrielson were the dominant species in summer. There were no attached populations, and perennation was ensured only by vegetative propagation. Characteristics of the outer cortex and chromatophores were useful for distinguishing the taxa at the species level and are recommended for recognition of sterile specimens.
DISTRIBUTION AND SYSTEMATICS OF BATRACHOSPERMUM (BATRACHOSPERMALES, RHODOPHYTA) IN NORTH AMERICA. 4. SECTION VIRESCENTIA1
Authors: Sheath Robert G. , Vis Morgan L. , Cole Kathleen M.
Published: October 2004

Thirty‐nine populations of Batrachospermum section Virescentia from North America were compared to eight type specimens and two historically important specimens using multivariate morphometrics and image analysis. From this analysis, two species are recognized: B. helminthosum Bory de Saint‐Vincent (syn. B. bruziense Sirodot, B. graibussoniense Sirodot, B. sirodotii Skuja ex Flint, B. testale Sirodot, B. virgatum Sirodot nom. illeg., and B. viride Sirodot) and B. elegans Sirodot (syn. B. coerulescens Sirodot nom. illeg.). In B. helminthosum trichogynes are cylindrical to slightly club‐shaped with few to no protuberances, whereas in B. elegans half to all of the trichogynes have one to three basal knobs or branches. None of the qualitative features previously used to separate species in this section were found to be of taxonomic value due to their universal presence; quantitative characteristics were highly variable and overlapped among specimens examined. Emended descriptions of both species are provided. Batrachospermum elegans was collected in northeastern U.S.A. and central Costa Rica, whereas B. helminthosum ranged from Nova Scotia to Louisiana and was collected in central Mexico, Costa Rica, and northwestern U.S.A. Batrachospermum julianum Arcangeli and B. transtaganum Reis, previously classified in section Virescentia, were observed to have twisted carpogonial branches and, therefore, should be placed in section Contorta. Sections Setacea and Virescentia of Batrachospermum differ in whorl size, ratio of carposporophyte height to whorl diameter, and trichogyne stalking; hence, we continue to recognize them as being distinct taxonomic entities as originally described.
ULTRASTRUCTURE AND PHYLOGENETIC RELATIONSHIPS OF CHAETOPELTIDALES ORD. NOV. (CHLOROPHYTA, CHLOROPHYCEAE)1
Authors: O'Kelly Charles J. , Watanabe Shin , Floyd Gary L.
Published: October 2004

Vegetative cells and zoospores of Hormotilopsis gelatinosa Trainor & Bold, H. tetravacuolaris Arce & Bold, Planophila terrestris Groover & Hofstetter, and Phyllogloea fimbriata (Korchikov) Silva were examined by transmission electron microscopy. All cells had pyrenoids traversed by cytoplasmic channels. Zoospores were quadriflagellate and had essentially cruciate flagellar apparatuses. Scales were present on free‐swimming zoospores. These features are essentially identical to those of Chaetopeltis sp. and are dissimilar to those of other described green algae. The new order Chaetopeltidales is created to accommodate the genera Chaetopeltis, Hormotilopsis, Planophila sensu Groover & Hofstetter, Phyllogloea, Dicranochaete, and Schizochlamys, organisms previously scattered among the orders Tetrasporales, Chloro‐coccales, Chlorosarcinales, and Chaetophorales. Members of the order are closely related to the ancestral chlorophycean flagellate genus Hafniomonas, may be ancestral with respect to other Chlorophyceae, and may also be closely related to the ulvophycean order Ulotrichales.