bluuebunny/crossref_metadata_2025 huggingface dataset:
Template‐free self‐assembling fullerene and lipopeptide conjugates of alamethicin form voltage‐dependent ion channels of remarkable stability and activity
Authors: Jung Günther , Redemann Thomas , Kroll Karsten , Meder Sabine , Hirsch Andreas , Boheim Günther
Published: November 2003

N‐ and C‐terminally modified with fullerene or lipopeptide alamethicin molecules were designed for the formation of template‐free, self‐assembling, voltage‐dependent ion conducting channels. The automated solid phase synthesis of the alamethicin‐F30 sequence was performed by in situ fluoride activation on 2‐chlorotritylchloride‐polystyrene resin and the conjugation with fullerenes‐C60 and ‐C70 was carried out in solution. Voltage‐dependent bilayer experiments revealed preferred channel sizes for C‐terminal alamethicin F30‐fullerene‐C60 and ‐C70 conjugates and higher activity compared with native alamethicin, whereas N‐terminally linked fullerene balls destabilize pore formation. C‐terminal alamethicin F30‐fullerene‐C70 conjugates show pore states with remarkably long lifetimes of seconds. C‐terminal lipopeptide conjugates of alamethicin were prepared by coupling via short peptide spacers with synthetic tripalmitoyl‐S‐glyceryl‐cysteine, which represents the strong membrane anchoring N‐terminus of bacterial lipoprotein. Alamethicin‐lipopeptide conjugates exhibit high channel forming activities, whereby they self‐assemble and adopt preferred pore states with extremely long lifetimes. The novel membrane modifying peptaibol constructs are valuable lead compounds for developments in sensorics related to transmembrane ion conductance. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Determination of the parameters of multidimension vibration Hamiltonian of CH3NH2 from quantum chemical data
Authors: Irgibaeva I. S.
Published: November 2003

The two large‐amplitude motions—NH2 wagging and CH3 internal rotation—take place in methylamine, CH3NH2. The complete set of potential and kinematic coupling constants, characterizing the Hamiltonian of a nonrigid molecule CH3NH2 with two large‐amplitude coordinates, is derived from standard quantum chemical data for the equilibrium geometries, normal frequencies, and eigenvectors in the ground and transition states. The reconstruction of the Hamiltonian is made via the following steps: classification of the generalized coordinates according to the irreducible representations of the group of the nonrigid molecular model; linear transformation of the ground‐state normal coordinates into the frame of the transition state taking into account the Eckart conditions; and perturbative solution of the inverse vibrational problem. It is shown that the consideration of interactions of large‐amplitude vibrations with transfer ones significantly affects the parameters of 2‐D potential. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Molecular dynamics of strained retinal in various electronic states
Authors: Egorova K. B. , Shaitan K. V. , Ermilov A. Y.
Published: November 2003

Internal rotation barriers in retinal and its protonated analog in the ground and first excited states were investigated. The Hartree–Fock method followed by Moeller–Plesset perturbation theory and molecular dynamic methods were applied. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Mixed quantum–classic intramolecular dynamics at light transformation by molecules
Authors: Morozov V. A. , Dubina Y. M. , Shorygin P. P.
Published: November 2003

The time‐dependent population probability of the excited electronic state in a two‐level electronic subsystem of a molecular model in the monochromatic light field is investigated by a mixed quantum–classic method. The dynamics of the electronic subsystem of the molecule, radiation field, and their interaction are described using the decay theory of closely coupled unstable states of quantum systems. The classic field‐free dynamics of nuclei are defined by Born–Oppenheimer quadratic potentials. Radiative coupling between “dressed” states and radiative decay of the excited electronic state of the molecule are taken into account. The differential equation of the second order by time for the probability amplitude of the excited electronic‐state population is obtained with the consistent description of the adiabatic dynamics of nuclei. The results of numerical computation of this equation were used to describe the time‐dependent population probability of the excited electronic state of the molecule in terms of “vertical” transitions between dressed states of a common system: the molecule and radiation field. On the basis of a few obtained examples of adiabatic modulation of the population of the excited electronic state, conclusions were made on corresponding intensity and spectrum of scattered radiation. The partial agreement and discrepancy of these conclusions in the frameworks of mixed quantum–classic theory with corresponding conclusions in the frameworks of rigorous quantum theory were pinpointed. The comparison severed as grounds for new conclusions concerning a degree of fitness of classic treatment of the nuclear dynamics of molecule under various conditions of light transformation by molecules. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Structure of the nitrosomethane molecule (CH3NO) in the ground electronic state: Testing of ab initio methods for the description of potential energy surface
Authors: Dolgov Eugeniy K. , Bataev Vadim A. , Godunov Igor A.
Published: November 2003

The equilibrium geometry, barrier to internal rotation, and harmonic and anharmonic vibrational frequencies of the CH3NO molecule in the ground electronic state were calculated by different modern quantum chemical techniques. Special attention was given to the problem of torsional motion. The dependence of the results of calculations on the atomic orbital and molecular orbital basis sets and correlated methods was examined. The results of calculations were compared with experimental data. Some methods provided excellent agreement with the experiment. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Paired comparisons of sensory pain adjectives
Authors: van Wijk Arjen J , Hoogstraten Johan
Published: November 2003

Background: Language is an important tool in the communication of pain. The most widely known verbal pain assessment tool is the McGill Pain Questionnaire (MPQ). The MPQ scoring procedure implies equal weights for different pain describing adjectives with the same rank value.

Aim: In the present study the relative intensity of the most severe sensory pain adjectives of the MPQ was examined by means of Thurstone's method of paired comparison.

Method: A questionnaire was constructed to run a balanced pairwise comparison experiment with pain describing adjectives obtained from the Dutch version of the MPQ. The questionnaire was filled out by psychology freshmen (N=528).

Results: Subjects were highly consistent in their choices regarding the paired comparisons but showed substantial individual differences with respect to agreement about the relative intensity of the adjectives. However, some adjectives were clearly rated as more painful than others, these were lancinating, bursting and tearing. Adjectives seen as relatively least painful were clasping, shooting and freezing.

Conclusions: The results suggest that the MPQ scoring procedure is not entirely consistent with the relative ranking obtained in the present study. The authors do not consider the extent of this deviation to be a violation of one of the MPQ's underlying assumptions.
Construct validity of the French version of the Dyadic Adjustment Scale
Authors: Vandeleur C. L. , Fenton B. T. , Ferrero F. , Preisig M.
Published: November 2003

The Dyadic Adjustment Scale (DAS) and its revised version (RDAS) are measures of the quality of dyadic relationships. The goal of this study was to assess the properties of the French version of this self-rating instrument by testing the most commonly proposed models of the English version using confirmatory factor analysis. Our study sample included 1,131 parents of school children recruited in the general population in the French-speaking part of Switzerland. Data analysis revealed an excellent fit of the unique-factor solution for both the DAS and RDAS. Alternatively, our analyses also showed a good fit for the hierarchical solution of the DAS. These results provide evidence for similar psychometric properties of the French version of the DAS as compared to the original English version.
Retrieval of precipitable water using Special Sensor Microwave/Temperature‐2 (SSM/T‐2) millimeter‐wave radiometric measurements
Authors: Manning W. , Wang J. R.
Published: November 2003

Four years of Special Sensor Microwave/Temperature‐2 (SSM/T‐2) measurements over the high‐latitude regions of both the Northern and Southern Hemispheres are used to retrieve precipitable water W < 0.8 cm. The retrieved W values compare well with several thousand near‐concurrent radiosonde‐derived estimates of W. Additionally, very good agreement is found between the retrieved SSM/T‐2 W values and continuous ground‐based radiometer‐derived estimates of W during a couple of extended time periods. A bias (0.03–0.06 cm) exists between the W values retrieved from the SSM/T‐2 and the values derived from the radiosonde/radiometer observations. This bias is caused primarily by the assumption of equivalent surface emissivity across the 150–183 GHz frequency range that is made during the development of the retrieval algorithm. The spatial distribution of the SSM/T‐2‐retrieved winter mean W values is examined together with digital elevation models for both the Greenland and Antarctic ice sheets. This detailed comparison conveys expected climatological characteristics that are quite sensible when the combined effects of the surface elevation and the general atmospheric circulation patterns near and over the ice sheets are considered in unison. The SSM/T‐2 W retrieval presented provides accurate W information with a high sampling rate for the potentially climate change‐sensitive polar regions of the Northern and Southern Hemispheres.
Electrical discharges and broadband radio emission by Martian dust devils and dust storms
Authors: Renno Nilton O. , Wong Ah‐San , Atreya Sushil K. , de Pater Imke , Roos‐Serote Maarten
Published: November 2003

Triboelectric charging of saltating and colliding sand and dust particles produces strong electric fields in terrestrial dust devils and dust storms. Acceleration of the charged particles, as well as microdischarges between them, generates wideband electromagnetic radiation. Similar phenomena are expected to be ubiquitous on Mars, because Martian dust devils and dust storms are larger, stronger and more frequent than their terrestrial analogues, and electrical discharges occur at a much lower potential gradient in the thin Martian atmosphere. We present theoretical arguments and observational evidence that Martian dust events produce nonthermal wideband electromagnetic radiation detectable from Earth.
The Sabotage of Patriarchy in Colonial Rhodesia, Rural African Women's Living Legacy to Their Daughters
Authors: Wells Julia C.
Published: November 2003

Evidence from a University of Zimbabwe oral history project suggests that many rural women in colonial Rhodesia played an active role in undermining patriarchal customs which they experienced as oppressive. These women defied family norms by choosing their own marriage partners, prioritizing the formal education of their daughters and finding ways to generate income to secure greater degrees of autonomy. This study compliments other research which depicts women's primary form of resistance to be moving from rural to urban areas, by showing what options some women exercised while remaining within rural society.
Vacant Wombs: Feminist Challenges to Psychoanalytic Theories of Childless Women
Authors: Hird Myra J.
Published: November 2003

This paper concerns a theoretical struggle to situate childless women within contemporary feminist debates about gender, the body and sexuality. Although psychoanalytic theory offers a compelling approach to the body, a Freudian account of childless women has largely escaped investigation. This paper will provide such an analysis, arguing that competing interpretations of psychoanalytic theory reveal a salient tension in the interpretation of gender identification. On the one hand, some theorists focus on a social development model of gender identification. This model emphasizes the sexual aim of reproduction as a salient feature of ‘normal’ gender identity development. In this paper, I argue this approach may pathologize childless women insofar as they ‘fail’ to socially develop in ways that conform to the imperative to sexually reproduce. On the other hand, a number of theorists argue against the foreclosure on gender identity that the social development model implies. An alternate interpretation of psychoanalytic theory calls attention to Freud's theory of ‘psychic bisexuality’ or ‘polymorphous perversity’. This notion invites a much more complex and ambivalent notion of gender identity as it emphasizes the temporal, fragile and incomplete process of gender identification. I aim to argue that this latter interpretation offers a space for childless women as it attempts to lay bare the hegemonic relationship between femininity and sexual reproduction. I draw upon the work of a number of feminist theorists who variously take up these central themes in Freudian psychoanalytic theory to further contest the reification of the association between femininity and maternity.
Effect of contact statistics on electrical contact resistance
Authors: Jang Yong Hoon , Barber J. R.
Published: November 2003

The flow of electrical current through a microscopic actual contact spot between two conductors is influenced by the flow through adjacent contact spots. A smoothed version of this interaction effect is developed and used to predict the contact resistance when the statistical size and spatial distribution of contact spots is known. To illustrate the use of the method, an idealized fractal rough surface is defined using the random midpoint displacement algorithm, and the size distribution of contact spots is assumed to be given by the intersection of this surface with a constant height plane. With these assumptions, it is shown that including finer scale detail in the fractal surface, equivalent to reducing the sampling length in the measurement of the surface, causes the predicted resistance to approach the perfect contact limit.
Excitonic properties of strained wurtzite and zinc-blende GaN/AlxGa1−xN quantum dots
Authors: Fonoberov Vladimir A. , Balandin Alexander A.
Published: November 2003

We investigate exciton states theoretically in strained GaN/AlN quantum dots with wurtzite (WZ) and zinc-blende (ZB) crystal structures, as well as strained WZ GaN/AlGaN quantum dots. We show that the strain field significantly modifies the conduction- and valence-band edges of GaN quantum dots. The piezoelectric field is found to govern excitonic properties of WZ GaN/AlN quantum dots, while it has a smaller effect on WZ GaN/AlGaN, and very little effect on ZB GaN/AlN quantum dots. As a result, the exciton ground state energy in WZ GaN/AlN quantum dots, with heights larger than 3 nm, exhibits a redshift with respect to the bulk WZ GaN energy gap. The radiative decay time of the redshifted transitions is large and increases almost exponentially from 6.6 ns for quantum dots with height 3 nm to 1100 ns for the quantum dots with height 4.5 nm. In WZ GaN/AlGaN quantum dots, both the radiative decay time and its increase with quantum-dot height are smaller than those in WZ GaN/AlN quantum dots. On the other hand, the radiative decay time in ZB GaN/AlN quantum dots is of the order of 0.3 ns, and is almost independent of the quantum-dot height. Our results are in good agreement with available experimental data and can be used to optimize GaN quantum-dot parameters for proposed optoelectronic applications.
Equilibrium and nonequilibrium molecular dynamics methods for determining solid–liquid phase coexistence at equilibrium
Authors: Ge Jialin , Wu Guang-Wen , Todd B. D. , Sadus Richard J.
Published: November 2003

The solid–liquid equilibrium phase transition of a one-component Lennard-Jones system is determined by equilibrium and nonequilibrium molecular dynamics simulation methods. One method uses the observation that the scaling exponent of the pressure or energy of a shearing Lennard-Jones liquid is approximately 1 at the solid phase. This enables us to locate the density of the coexisting solid phase. The coexisting liquid phase density is then obtained by constructing a tie line between the coexisting solid phase point and the liquid phase curve. Alternatively, the coexisting liquid phase density can be efficiently obtained by observing the change in pressure as a function of strain rate and density. The coexisting solid phase density can be then obtained from a tie line from the liquid curve to the solid curve. These calculations are the first reported use of combined equilibrium and nonequilibrium molecular dynamics methods for phase coexistence at equilibrium. Our results are in very good agreement with those obtained by alternative simulation methods for phase equilibria.
Quantum mechanical effects on random oxide thickness and random doping induced fluctuations in ultrasmall semiconductor devices
Authors: Andrei Petru , Mayergoyz Isaak
Published: November 2003

Quantum mechanical effects on fluctuations in ultrasmall semiconductor devices are studied. Quantum mechanical effects are included in the analysis by using the density gradient model, for which the main parameters (effective masses) are identified through the two-dimensional Schrödinger equation. A very fast technique for the computation of threshold voltage fluctuations induced by random oxide thickness and doping variations is proposed. This technique is based on linearization of the transport equations with respect to the fluctuating quantities. This technique is computationally very efficient because it avoids numerous simulations for various doping and oxide realizations (as in the case of Monte Carlo techniques). At the same time, it provides information about the sensitivity of threshold voltage to the fluctuations of oxide thicknesses and doping at different locations. Sample simulation results are reported and compared with those previously published and good agreement is observed.
Self-induced oscillations in the shock wave flow pattern formed in a stationary supersonic flow over a double wedge
Authors: Ben-Dor G. , Vasilev E. I. , Elperin T. , Zenovich A. V.
Published: November 2003

Numerical simulations of a two-dimensional supersonic flow of an inviscid perfect gas over a double wedge in the Mach numbers range 5⩽M⩽9, revealed the existence of self-induced oscillations in the shock wave flow pattern in a narrow range of geometrical parameters.
Direct measurement of nanoscale sidewall roughness of optical waveguides using an atomic force microscope
Authors: Jang J. H. , Zhao W. , Bae J. W. , Selvanathan D. , Rommel S. L. , Adesida I. , Lepore A. , Kwakernaak M. , Abeles J. H.
Published: November 2003

An atomic force microscope (AFM) with an ultrasharp tip was used to directly measure the sidewall profile of InP/InGaAsP waveguide structures etched using an inductively coupled plasma reactive ion etching (ICP-RIE) in Cl2-based plasma. A special staircase pattern was devised to allow AFM tip to access the etched sidewall of the waveguides in the normal direction. Statistical information such as correlation length and rms roughness of the sidewall profile obtained through three-dimensional imaging by AFM has been presented. rms roughness as low as 3.45 nm was measured on the sidewall of 4-μm-deep etched InP/InGaAsP heterostructures.
Differently anchored influenza hemagglutinin mutants display distinct interaction dynamics with mutual rafts
Authors: Shvartsman Dmitry E. , Kotler Mariana , Tall Renee D. , Roth Michael G. , Henis Yoav I.
Published: November 2003

Lipid rafts play important roles in cellular functions through concentrating or sequestering membrane proteins. This requires proteins to differ in the stability of their interactions with lipid rafts. However, knowledge of the dynamics of membrane protein–raft interactions is lacking. We employed FRAP to measure in live cells the lateral diffusion of influenza hemagglutinin (HA) proteins that differ in raft association. This approach can detect weak interactions with rafts not detectable by biochemical methods. Wild-type (wt) HA and glycosylphosphatidylinositol (GPI)-anchored HA (BHA-PI) diffused slower than a nonraft HA mutant, but became equal to the latter after cholesterol depletion. When antigenically distinct BHA-PI and wt HA were coexpressed, aggregation of BHA-PI into immobile patches reduced wt HA diffusion rate, suggesting transient interactions with BHA-PI raft patches. Conversely, patching wt HA reduced the mobile fraction of BHA-PI, indicating stable interactions with wt HA patches. Thus, the anchoring mode determines protein–raft interaction dynamics. GPI-anchored and transmembrane proteins can share the same rafts, and different proteins can interact stably or transiently with the same raft domains.
Interactions between Sec Complex and Prepro-α-Factor during Posttranslational Protein Transport into the Endoplasmic Reticulum
Authors: Plath Kathrin , Wilkinson Barrie M. , Stirling Colin J. , Rapoport Tom A.
Published: November 2003

Posttranslational translocation of prepro-α-factor (ppαF) across the yeast endoplasmic reticulum membrane begins with the binding of the signal sequence to the Sec complex, a membrane component consisting of the trimeric Sec61p complex and the tetrameric Sec62p/63p complex. We show by photo-cross-linking that the signal sequence is bound directly to a site where it contacts simultaneously Sec61p and Sec62p, suggesting that there is a single signal sequence recognition step. We found no evidence for the simultaneous contact of the signal sequence with two Sec61p molecules. To identify transmembrane segments of Sec61p that line the actual translocation pore, a late translocation intermediate of ppαF was generated with photoreactive probes incorporated into the mature portion of the polypeptide. Cross-linking to multiple regions of Sec61p was observed. In contrast to the signal sequence, neighboring positions of the mature portion of ppαF had similar interactions with Sec61p. These data suggest that the channel pore is lined by several transmembrane segments, which have no significant affinity for the translocating polypeptide chain.
Long-Term Enhanced Expression of Heat Shock Proteins and Decelerated Apoptosis in Polymorphonuclear Leukocytes from Major Burn Patients
Authors: Ogura Hiroshi , Hashiguchi Naoyuki , Tanaka Hiroshi , Koh Taichin , Noborio Mitsuhiro , Nakamori Yasushi , Nishino Masato , Kuwagata Yasuyuki , Shimazu Takeshi , Sugimoto Hisashi
Published: November 2003

Heat shock proteins (HSPs), as molecular chaperones, have been reported to protect cells against a variety of environmental stresses. The objective of this study was to clarify the serial changes in expression of HSPs, oxidative activity, and apoptosis in polymorphonuclear leukocytes (PMNLs) from burn patients. Eight patients with severe burns (mean burn index 24.0 ± 6.1) were included. Blood samples were serially obtained at five time points: days 0 to 1, days 2 to 7, days 8 to 14, days 15 to 21, and days 22 to 28. We measured expressions of HSP27, HSP60, HSP70, and HSP90 in permeabilized PMNLs by flow cytometry with the use of a monoclonal antibody against each HSP. The oxidative activity and apoptosis in PMNLs were also measured by flow cytometry. During all five time periods, expressions of HSP27, HSP60, and HSP70 in PMNLs from burn patients were significantly greater than those in PMNLs from healthy volunteers. The expression of HSP90 in PMNLs of burn patients increased between days 2 and 21. Oxidative activity in their PMNLs was significantly enhanced between days 2 and 28, and PMNL apoptosis was markedly inhibited for as long as 4 weeks after thermal injury. In conclusion, major burn causes long-term, enhanced expression of HSPs in PMNLs along with increased oxidative activity and decelerated apoptosis. The enhanced expression of HSPs may regulate the oxidative stress response and life-span of PMNLs in burn patients.
Endogenous Production of Heparin-Binding EGF-Like Growth Factor During Murine Partial-Thickness Burn Wound Healing
Authors: Cribbs Randolph K. , Harding Paul A. , Luquette Mark H. , Besner Gail E.
Published: November 2003

Heparin-binding EGF-like growth factor (HB-EGF), a potent epithelial cell mitogen, has been identified in human burn blister fluid and excised human burn wounds. Topical application of HB-EGF to murine partial-thickness scald burns accelerated reepithelialization, increased keratinocyte proliferation, and enhanced production of endogenous transforming growth factor-α in the healing wounds. The goal of the present study was to examine the production of endogenous HB-EGF and transforming growth factor-alpha (TGF-α) in a murine partial-thickness scald burn model. Keratinocyte proliferation was assessed by 5-bromo-deoxyuridine incorporation, and tissue sections were examined by in situ hybridization for HB-EGF mRNA expression and by immunohistochemistry for HB-EGF and TGF-α production. HB-EGF mRNA expression and production of HB-EGF and TGF-α proteins by both marginal surface keratinocytes and hair follicle epithelial cells reached a maximum by postburn day five and decreased thereafter. This corresponded to the peak period of keratinocyte proliferation. We conclude that HB-EGF and TGF-α act in conjunction to stimulate wound healing following thermal injury.
Use of a Token Reinforcement System to Promote Appropriate Behavior at a Pediatric Burn Summer Camp
Authors: Adams C. D. , Girolami P. A. , Joseph K. E. , Sauvageot S. A. , Slater H.
Published: November 2003

Child behavior management can be an important concern in conducting summer camps for pediatric burn patients, because many of these patients have a history of significant behavioral difficulties. To be efficient, a flexible camp-wide behavior management system, such as a token economy, would be ideal. In this article we discuss the concept and principles of a token reinforcement system and outline how this intervention was applied to our pediatric burn summer camp across 2 consecutive years. We also provide a description of modifications made for the second camp, based on counselor ratings of and our experience with the token system during the first camp. Results from counselor assessments indicated that after using the token system, counselors' perceptions of its utility (eg, effective in decreasing problem behavior in campers, useful in making behavior management easier) increased significantly across both years.
Long-Term Trends in Mortality According to Age Among Adult Burn Patients
Authors: McGwin Gerald , Cross James M. , Ford Jeremy W. , Rue Loring W.
Published: November 2003

The purpose of this study was to evaluate differences in mortality among adult burn patients over a 25-year period according to age. All patients admitted to a regional burn center between 1973 and 1997 were divided into three age groups (18–34, 35–54, and 55 and older), and mortality rates were compared over time. Between 1973 and 1997, the proportion of patients in each age group remained consistent, as did the type of burns. The average total body surface area burned declined steadily from 31.6% in the 1970s to 18.2% in the late 1990s. The absolute change in mortality was small (7.7%), moderate (16.3%), and large (30.2%) in the young, middle-aged, and old, respectively. However, the relative change demonstrated the opposite pattern. The results of this study suggest that declines in mortality among adult burn patients have occurred across the age spectrum over the past 25 years.
Effect of a Supervised Exercise and Physiotherapy Program on Surgical Interventions in Children with Thermal Injury
Authors: Celis Mario M. , Suman Oscar E. , Huang Ted T. , Yen Peter , Herndon David N.
Published: November 2003

Continuous body growth and rigidity of scars in children are significant contributors to burn scar contractures (BSCs). BSCs decrease a patient's range of motion and their ability to perform activities of daily living. A benefit of exercise is an increase the patient's ability to perform and sustain activities of daily living. Therefore, we investigated whether patients who were involved in a supervised, hospital-based exercise program, in addition to physical and occupational therapy (PTEX), would have fewer surgical interventions than a nonexercise group receiving home-delivered physical and occupational therapy (PT) alone. We examined 53 patients at 6, 9, 12, 18, and 24 months postburn. The PTEX group (n = 27) completed a 12-week supervised exercise program starting at 6 months postburn. Exercise sessions were held three times per week, with duration of 60 to 90 minutes per session. Resistance and aerobic exercises were performed at 70 to 85% of the patient's maximal effort. In contrast, the PT group (n = 26) received a home rehabilitation program with no supervised exercise. Patients were evaluated at 3-month intervals for scar formation, range of motion, and need for surgery. At 12, 18, 24 months postburn, the number of patients in the PTEX group needing release of BSC was significantly lower than the number of patients in the PT group. The results indicate that patients would receive a significant benefit if enrolled in a supervised exercise and physiotherapy program with the exercise portion consisting of an aerobic and resistance-training component. This type of program is beneficial in decreasing the number of surgical interventions and should be incorporated as part of a postburn outpatient rehabilitation.
Endothelin Receptor Antagonist Increases Cerebral Perfusion and Reduces Ischaemic Damage in Feline Focal Cerebral Ischaemia
Authors: Patel Toshal R. , Galbraith Samuel , Graham David I. , Hallak Hussein , Doherty Annette M. , McCulloch James
Published: November 2003

These investigations characterised the cerebrovascular effects of an endothelin ETA-receptor antagonist PD156707 in normal and ischaemic cat brain. A dose of PD156707 that inhibited the effects of exogenous endothelin-1 was established in nonischaemic cerebral resistance arterioles. Perivascular microapplication of the endothelin–receptor antagonist PD156707 (0.03–3 μ M) had a minimal effect on nonischaemic pial resistance arterioles. The perivascular coapplication of PD156707 and ET-1 (10 n M) effected a dose-dependent attenuation of the ET-1 vasoconstrictive response (IC50 = 0.1 μ M). Intravenous administration of PD156707 (3 μmol/kg bolus + 5 μmol/kg/h infusion) attenuated the vasoconstriction elicited by perivascular ET-1 (10 n M) in normal pial arterioles (ET-1 vasoconstriction: −37 ± 13% from preinjection baseline; after intravenous PD156707: 6 ± 10% from preinjection baseline). In the focal ischaemia studies, cerebral perfusion was measured in the suprasylvian and ectosylvian gyri (by laser Doppler flowmetry). Occlusion of the middle cerebral artery reduced cerebral perfusion in the suprasylvian and ectosylvian gyri by ∼50%. Intravenous administration of PD156707 (3 μmol/kg bolus + 5 μmol/kg/h infusion), initiated 30 min after middle cerebral artery occlusion, effected a progressive increase in cerebral perfusion up to preocclusion baseline levels, whereas cerebral perfusion in vehicle-treated animals did not vary from its postocclusion level. In these animals, the intravenous administration of PD156707 reduced the hemispheric volume of ischaemic damage by 45% (vehicle: 2,376 ± 1,107 mm3; PD156707: 1,307 ± 548 mm3; p < 0.05). Our investigations indicate that endothelin receptor antagonism may be a new therapeutic strategy for the amelioration of focal ischaemic damage.
Systemic Nitric Oxide Synthase Inhibition Does Not Affect Brain Oxygenation during Cortical Spreading Depression in Rats: A Noninvasive Near-Infrared Spectroscopy and Laser-Doppler Flowmetry Study
Authors: Wolf Tilo , Lindauer Ute , Obrig Hellmuth , Dreier Jens , Back Tobias , Villringer Arno , Dirnagl Ulrich
Published: November 2003

Cortical spreading depression (CSD) has been implicated in the migraine aura and in stroke. This study demonstrates near-infrared spectroscopy (NIRS) for the first time as capable of noninvasive on-line detection of CSD in the pentobarbital-anesthetized rat. CSD was accompanied by a brief and rapid increase of regional CBF (by laser-Doppler flowmetry) to 200–400% baseline. NIRS demonstrates that this hyperperfusion is associated with concentration increases of oxyhemoglobin, while deoxyhemoglobin decreases. Simultaneously, oxygen partial pressure, measured on the brain surface with a solid-state Polarographic probe, was shown to be raised by at least 14 mm Hg during CSD. Oxygen-dependent phosphorescence life-time quenching measurements confirmed this finding. NIRS data on cytochrome aa3, however, showed a CSD-related shift toward a more reduced state, despite raised blood oxygenation. This may suggest either limited O2 transport from the blood to mitochondria or decreased oxygen utilization during CSD as supposed by theories about compartmentalization of energy metabolism favoring glycolytic rather than aerobic energy supply during CSD. However, the data on cytochrome aa3, warrant caution and are discussed critically. Nitric oxide synthase inhibition by systemic application of N′-nitro-l-arginine had no significant effect on the perfusion response or the tissue Po2 during CSD. During most CSD episodes, a brief decrease in MABP by 4–8 mm Hg was noted that might be caused by functional decortication during CSD.
Neuronal Protection from Cerebral Ischemia by Synthetic Fibronectin Peptides to Leukocyte Adhesion Molecules
Authors: Yanaka Kiyoyuki , Camarata Paul J. , Spellman Stephen R. , McCarthy James B. , Furcht Leo T. , Low Walter C. , Heros Roberto C.
Published: November 2003

Leukocytes play an important role in the development of ischemia/reperfusion injury. Recent work in our laboratory has demonstrated that a mixture of synthetic fibronectin peptides to leukocyte adhesion molecules reduces ischemic brain damage after transient focal cerebral ischemia. The purpose of this study was to evaluate the efficacy of the individual peptides on leukocyte accumulation, infarct size, and neurological outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Thirty-five animals were divided into five groups: transient ischemia without treatment (Group I), treatment with arginyl-glycyl-aspartic acid (RGD) peptide (Group II), connecting segment (CS)-1 peptide (Group III), fibronectin (FN)-C/H-V peptide (Group IV), and scrambled FN-C/H-V peptide (Group V). Groups III and IV showed a significant decrease in the degree of leukocyte infiltration in the lesion and in the infarct size ( p < 0.05) when compared to Groups I, II, and V. The neurological grade of Groups III and IV was significantly better than in Groups I, II, and V at 48 h after reperfusion ( p < 0.01). Thus, in addition to demonstrating the potential efficacy of synthetic peptides as therapeutic agents for ischemia-reperfusion, these results also offer new insights into the mechanisms of leukocyte arrest and recruitment in ischemia/reperfusion injury.
E-Selectin in Focal Cerebral Ischemia and Reperfusion in the Rat
Authors: Zhang Rui Lan , Chopp Michael , Zhang Zheng G. , Phillips M. Laurie , Rosenbloom Craig L. , Cruz Rebecca , Manning Anthony
Published: November 2003

The selectin family of glycoproteins facilitates the early phase of polymorphonuclear leukocyte adhesion to the endothelial cell and, thus, may promote ischemic cell damage. To evaluate E-selectin in the pathogenesis of focal cerebral ischemia and reperfusion injury, we cloned rat E-selectin cDNA and measured the temporal profiles E-selectin mRNA (Northern blot) and protein (immunohistochemistry) during (1 h of ischemia) and after (up to 1 week) transient (2 h) middle cerebral artery (MCA) occlusion in the male Wistar rat. We also tested the effect on these rats of administration of CY-1503, an analog of sialyl Lewisx (SLex), on ischemia cell damage. mRNA for E-selectin was first detected in the ischemic hemisphere at 2 h of reperfusion and persisted to 46 h of reperfusion. E-selectin (protein) was localized to microvessels within the ischemic lesion at 0 h of reperfusion and persisted to 70 h of reperfusion. Treatment of the ischemic animals with CY-1503 (50 mg/kg) (n = 8) significantly reduced infarct volume by 42% ( p < 0.05) and significantly reduced myeloperoxidase immunoreactive cells in the ischemic lesion by 60% ( p < 0.05). These findings provide the first direct evidence for the involvement of E-selectin in transient MCA occlusion in rats and suggest that the E-selectin may facilitate neutrophil adhesion and subsequent cerebral ischemic cell damage.
Interleukin-1 Mediates Induction of Tolerance to Global Ischemia in Gerbil Hippocampal CA1 Neurons
Authors: Ohtsuki Toshiho , Ruetzler Christi A. , Tasaki Kaoru , Hallenbeck John M.
Published: November 2003

A series of experiments was performed to determine the role of interleukin (IL)-1 in the induction of tolerance to global ischemia in Mongolian gerbils. In Group I, a 2-min “preconditioning” ischemia protected CA1 hippocampal neurons in gerbils subjected to 3.5 min ischemia 3 days later. CA1 neuronal density was: sham, 171 ± 3/mm; 3.5 min ischemia, 30 ± 30/mm; 2 and 3.5 min ischemia 162 ± 6/mm. Experiments in Group II addressed the role of IL-1 in the induction of tolerance by sublethal ischemia. Arterial IL-1α and IL-Iβ became elevated between 1 and 3 days after a 2-min ischemic exposure. IL-1α was: sham, 6.4 ± 0.6 ng/ml; and 2-day, 10.2 ± 1.2 ng/ml. IL-1β was: sham, 6.4 ± 0.5 ng/ml; and 2-day, 17.3 ± 2 ng/ml. Recombinant human IL-1 receptor antagonist (IL-1ra) i.p. blocked ischemic tolerance induction by 2-min preconditioning ischemia: 2-min ischemia + vehicle, 162 ± 6/mm; and 2-min ischemia + IL-1ra, 67 ± 17/mm. Experiments in Group III assessed the capacity of IL-1 to induce tolerance to brain ischemia. IL-1α i.p. (0, 10, 20 μg/kg) for 3 days prior to 3.5-min forebrain ischemia provided significant CA1 neuroprotection in a dose-dependent manner: 2 ± 2, 68 ± 83, and 129 ± 42/mm, respectively. IL-1β (15 μg/kg) in combination with either IL-1ra (100 mg/kg) or IL-1ra vehicle i.p. on the same schedule demonstrated a significant CA1 neuroprotection that could be nullified by IL-1ra: IL-1β + IL-1ra vehicle, 153 ± 16/mm; and IL-1β + IL-1ra, 67 ± 36/mm. Recognition that tolerance arises from stimulation of a known receptor (IL-1RI) permits molecular analysis of the intracellular signaling that is critical for production of that state.
Cytotoxic Fragment of Amyloid Precursor Protein Accumulates in Hippocampus after Global Forebrain Ischemia
Authors: Yokota Masayuki , Saido Takaomi C. , Tani Eiichi , Yamaura Ikuya , Minami Nobutaka
Published: November 2003

We developed an antibody specific to β-amyloid precursor protein (βAPP) fragments possessing the exact amino terminus of the β-amyloid peptide and examined its induction in postischemic hippocampus. In control hippocampus, this APP fragment was lightly observed in pyramidal neurons of CA sectors and dentate granule cells. Transient forebrain ischemia enhanced accumulation of the APP fragment in CA1 pyramidal neurons. Seven days after the ischemia, while the APP fragment was still observed in dentate granule cells and CA3 neurons, it disappeared in dead CA1 neurons. While astrocytes did not show in any immunoreactivity throughout the experiment, those in the CA1 sector showed moderate immunoreactivity 7 days after the ischemia. The APP fragment has a cytotoxic effect on cultured neurons. These results suggest that the accumulation of the cytotoxic APP fragment in CA1 neurons may play a role in the development of delayed neuronal death after the ischemic insult.
Tests for Comparing Images Based on Randomization and Permutation Methods
Authors: Arndt Stephan , Cizadlo Ted , Andreasen Nancy C. , Heckel Dan , Gold Sherri , O'Leary Daniel S.
Published: November 2003

Tests comparing image sets can play a critical role in PET research, providing a yes-no answer to the question “Are two image sets different?” The statistical goal is to determine how often observed differences would occur by chance alone. We examined randomization methods to provide several omnibus test for PET images and compared these tests with two currently used methods. In the first series of analyses, normally distributed image data were simulated fulfilling the requirements of standard statistical tests. These analyses generated power estimates and compared the various test statistics under optimal conditions. Varying whether the standard deviations were local or pooled estimates provided an assessment of a distinguishing feature between the SPM and Montreal methods. In a second series of analyses, we more closely simulated current PET acquisition and analysis techniques. Finally, PET images from normal subjects were used as an example of randomization. Randomization proved to be a highly flexible and powerful statistical procedure. Furthermore, the randomization test does not require extensive and unrealistic statistical assumptions made by standard procedures currently in use.
Experimental Cerebral Venous Thrombosis: Evaluation Using Magnetic Resonance Imaging
Authors: Röther Joachim , Waggie Kim , van Bruggen Nick , de Crespigny Alexander J. , Moseley Michael E.
Published: November 2003

Diffusion-weighted (DWI), dynamic contrast-enhanced (perfusion imaging), and conventional spin-echo magnetic resonance imaging (MRI) were applied to characterize the pathophysiology of cerebral venous thrombosis (CVT) in the rat. We induced CVT by rostral and caudal ligation of the superior sagittal sinus (SSS) and injection of a thrombogenic cephalin suspension. The resulting pathology was monitored in an acute and long-term study group. Evans blue and hematoxylin–eosin staining was performed for comparison with MRI data. A subgroup of animals was treated with i.v. tissue plasminogen activator (t-PA). Successful thrombosis of the SSS was confirmed by macropathology or histopathology in all rats. Parenchymal lesions as shown by MRI, however, were present only in animals with additional involvement of cortical cerebral veins (11 of 18 rats). The early pathology was clearly detected with the DWI. The apparent diffusion coefficient declined to 56 ± 7% of control value at 0.5 h and slowly increased to 84 ± 8% by 48 h. Perfusion imaging showed parasagittal perfusion deficits. Treatment with t-PA partially resolved the hyperintensity on DWI. Evidence of blood–brain-barrier disruption was observed 2 to 3 h after induction of CVT. In conclusion, experimental CVT is characterized by early cytotoxic edema closely followed by vasogenic edema. The t-PA treatment partially reversed the DWI signal changes consistent with regional tissue recovery, as shown by histopathology. These results encourage the use of cytoprotective drugs in addition to anticoagulant or thrombolytic therapy.
Deep Prepiriform Cortex Modulates Neuronal Cell Death in Global Ischemia
Authors: Kawaguchi Kenji , Simon Roger P.
Published: November 2003

Deep prepiriform cortex has an important role in modulating neurotransmission during limbic seizures. We used pharmacologic blockade of non- N-methyl-D-aspartate (NMDA) receptors to study excitatory circuitry from the deep prepiriform cortex to the hippocampus during global ischemia in rat. NBQX, a potent non-NMDA glutamate receptor antagonist, was microinjected stereotactically into the deep prepiriform cortex before global ischemia for 10 min. Neuronal cell death in the hippocampus was evaluated quantitatively 72 h after ischemia. The NBQX-injected rats had a greater number of surviving cells in CA1 sector of hippocampus than did saline-injected controls or rats that received NBQX injections 1 mm from the target. Thus, excitatory amino acid-mediated circuitry emanating from deep prepiriform cortex modulates ischemic neuronal injury in the hippocampus.
Noninvasive Quantitative Measurements of Regional Cerebral Blood Flow Using Technetium-99m-L,L-ECD SPECT Activated with Acetazolamide: Quantification Analysis by Equal-Volume-Split 99mTc-ECD Consecutive SPECT Method
Authors: Takeuchi Ryo , Matsuda Hiroshi , Yonekura Yoshiharu , Sakahara Harumi , Konishi Junji
Published: November 2003

Resting- and acetazolamide (Acz)-activated-regional cerebral blood flow (rCBF) measurements were performed by consecutive single-photon emission computed tomography (SPECT) studies before and after Acz administration using equal-volume-split technetium-99m-L,L-ethyl cysteinate dimer. Quantitative rCBF images were converted from qualitative axial SPECT images by the application of Patlak plot graphical analysis with radionuclide angiography and Lassen's linearization correction. Total time span required for this study was 53 minutes. The unaffected side of 37 studies with unilateral vascular lesions and 45 studies without apparent vascular lesions showed 132 ± 17% and 140 ± 15% increase of mean CBF (mCBF), respectively, under Acz administration. Comparing these values, the Acz-activated rCBF increases of less-affected and affected hemispheres of 23 studies with bilateral vascular lesions (116 ± 13% and 113 ± 12%, respectively) was lower with high statistical significance ( P < 0.001). For the other 20 cases, physiologic saline was administered instead of Acz. This group showed no changes in mCBF under placebo administration (after placebo/baseline; 100 ± 6%). Acetazolamide-activated rCBF increase was recognized clearly and easily using quantitative images. This noninvasive method is easy to perform and may be helpful to detect regional abnormalities of hemodynamic reserve in cerebrovascular diseases.
Effect of Brain Ischemia and Reperfusion on the Localization of Phosphorylated Eukaryotic Initiation Factor 2α
Authors: DeGracia Donald J. , Sullivan Jonathon M. , Neumar Robert W. , Alousi Sarah S. , Hikade Katie R. , Pittman Joel E. , White Blaine C. , Rafols José A. , Krause Gary S.
Published: November 2003

Postischemic brain reperfusion is associated with a substantial and long-lasting reduction of protein synthesis in selectively vulnerable neurons. Because the overall translation initiation rate is typically regulated by altering the phosphorylation of serine 51 on the α-subunit of eukaryotic initiation factor 2 (eIF-2α), we used an antibody specific to phosphorylated eIF-2α [eIF-2(αP)] to study the regional and cellular distribution of eIF-2(αP) in normal, ischemic, and reperfused rat brains. Western blots of brain postmitochondrial supernatants revealed that ~1% of all eIF-2α is phosphorylated in controls, eIF-2(αP) is not reduced by up to 30 minutes of ischemia, and eIF-2(αP) is increased ~20-fold after 10 and 90 minutes of reperfusion. Immunohistochemistry shows localization of eIF-2(αP) to astrocytes in normal brains, a massive increase in eIF-2(αP) in the cytoplasm of neurons within the first 10 minutes of reperfusion, accumulation of eIF-2(αP) in the nuclei of selectively vulnerable neurons after 1 hour of reperfusion, and morphology suggesting pyknosis or apoptosis in neuronal nuclei that continue to display eIF-2(αP) after 4 hours of reperfusion. These observations, together with the fact that eIF-2(αP) inhibits translation initiation, make a compelling case that eIF-2(αP) is responsible for reperfusion-induced inhibition of protein synthesis in vulnerable neurons.