bluuebunny/crossref_metadata_2025 huggingface dataset:
STRATEGIC POSTURE, TECHNOLOGY STRATEGY AND PERFORMANCE AMONG SMALL FIRMS
Authors: GIBBONS PATRICK T. , O'CONNOR TONY
Published: October 2004

This paper investigates the performance effects of both aggressive technological posture and automation in a sample of 336 small and medium-sized enterprises. The paper seeks to test whether firm strategic posture mediates the relationship between technology policy and firm performance. Findings suggest that strategic posture does not mediate the relationship between technology policy and ROI, but does mediate the relationship between technology policy and sales growth.
FUNDAMENTALS OF PLANARIAN REGENERATION
Authors: Reddien Peter W. , Alvarado Alejandro Sánchez
Published: October 2004

▪ Abstract  The principles underlying regeneration in planarians have been explored for over 100 years through surgical manipulations and cellular observations. Planarian regeneration involves the generation of new tissue at the wound site via cell proliferation (blastema formation), and the remodeling of pre-existing tissues to restore symmetry and proportion (morphallaxis). Because blastemas do not replace all tissues following most types of injuries, both blastema formation and morphallaxis are needed for complete regeneration. Here we discuss a proliferative cell population, the neoblasts, that is central to the regenerative capacities of planarians. Neoblasts may be a totipotent stem-cell population capable of generating essentially every cell type in the adult animal, including themselves. The population properties of the neoblasts and their descendants still await careful elucidation. We identify the types of structures produced by blastemas on a variety of wound surfaces, the principles guiding the reorganization of pre-existing tissues, and the manner in which scale and cell number proportions between body regions are restored during regeneration.
MEMBRANE DOMAINS
Authors: Mukherjee Sushmita , Maxfield Frederick R.
Published: October 2004

▪ Abstract  Considerable evidence shows that lateral inhomogeneities in lipid composition and physical properties exist in biological membranes. These membrane lipid domains are proposed to play important roles in processes such as signal transduction and membrane traffic. However, there is not at present an adequate description of the nature of these lipid domains in terms of their size, abundance, composition, or dynamics. We discuss the current analyses of the properties and function of membrane domains in cells and compare their properties with chemically simpler model membrane systems that can be understood in greater detail.
CELL BIOLOGY OFMYCOBACTERIUM TUBERCULOSISPHAGOSOME
Authors: Vergne Isabelle , Chua Jennifer , Singh Sudha B. , Deretic Vojo
Published: October 2004

▪ Abstract  Phagocytosis and phagolysosome biogenesis represent fundamental biological processes essential for proper tissue homeostasis, development, elimination of invading microorganisms, and antigen processing and presentation. Phagosome formation triggers a preprogramed pathway of maturation into the phagolysosome, a process controlled by Ca2+and the regulators of organellar trafficking centered around the small GTP-binding proteins Rabs and their downstream effectors, including lipid kinases, organellar tethering molecules, and membrane fusion apparatus. Mycobacterium tuberculosis is a potent human pathogen parasitizing macrophages. It interferes with the Rab-controlled membrane trafficking and arrests the maturing phagosome at a stage where no harm can be done to the pathogen while the delivery of nutrients and membrane to the vacuole harboring the microorganism continues. This process, referred to as the M. tuberculosis phagosome maturation arrest or inhibition of phagosome-lysosome fusion, is critical for M. tuberculosis persistence in human populations. It also provides a general model system for dissecting the phagolysosome biogenesis pathways. Here we review the fundamental trafficking processes targeted by M. tuberculosis and the mycobacterial products that interfere with phagosomal maturation.
CHEMOATTRACTANT SIGNALING IN DICTYOSTELIUM DISCOIDEUM
Authors: Manahan Carol L. , Iglesias Pablo A. , Long Yu , Devreotes Peter N.
Published: October 2004

▪ Abstract  Dictyostelium is an accessible organism for studies of signaling via chemoattractant receptors. Chemoattractant-mediated signaling events and components are reviewed and presented as a series of connected modules, including excitation, inhibition, G protein–independent responses, early gene expression, inositol lipids, PH domain-containing proteins, cyclic AMP signaling, polarization acquisition, actin polymerization, and cortical myosin. The network incorporates information from biochemical, genetic, and cell biological experiments carried out on living cells. The modules and connections represent current understanding, and future information is expected to modify and build upon this structure.
DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS
Authors: De Robertis Edward M. , Kuroda Hiroki
Published: October 2004

▪ Abstract  We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear β-Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal β-Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulin-like growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.
CELLULAR LENGTH CONTROL SYSTEMS
Authors: Marshall Wallace F.
Published: October 2004

▪ Abstract  The problem of organelle size control can be addressed most simply by considering cellular structures that are linear, so that their size can be defined by a single parameter: length. We compare existing studies on several linear biological structures including prokaryotic flagella and flagellar hooks, eukaryotic flagella, sarcomere thin filaments, and microvilli. In some cases, existing evidence strongly supports the idea that length control involves a molecular ruler, in which the size of the overall structure is compared with the size of an individual molecule. In other cases, length control is likely to involve a steady-state balance of assembly and disassembly, in which one or the other rate is inherently length dependent. The lessons learned from size control in linear structures should be applicable to organelles with more complex three-dimensional structures.
THE ADENOMATOUS POLYPOSIS COLI PROTEIN: The Achilles Heel of the Gut Epithelium
Authors: Näthke Inke S.
Published: October 2004

▪ Abstract  The Adenomatous Polyposis coli (APC) gene is mutated or lost in most colon cancers, and the APC protein has emerged as a multifunctional protein that is not only involved in the Wnt-regulated degradation of β-catenin, but also regulates cytoskeletal proteins and thus plays a role in cell migration, cell adhesion, and mitosis. The gut epithelium is uniquely dependent on an intricate balance between a number of fundamental cellular processes including migration, differentiation, adhesion, apoptosis, and mitosis. In this review, I discuss the molecular mechanisms that govern the various functions of APC and their relationship to the role of APC in colon cancer.
Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep
Authors: Jo J. A. , Blasi A. , Valladares E. , Juarez R. , Baydur A. , Khoo M. C. K.
Published: October 2004

Heart rate variability (HRV) is mediated by at least three primary mechanisms: 1) vagal feedback from pulmonary stretch receptors (PSR), 2) central medullary coupling between respiratory and cardiovagal neurons (RCC), and 3) arterial baroreflex (ABR)-induced fluctuations. We employed a noninvasive experimental protocol in conjunction with a minimal model to determine how these sources of HRV are altered in obstructive sleep apnea syndrome (OSAS). Respiration, heart rate, and blood pressure were monitored in eight normal subjects and nine untreated OSAS patients in relaxed wakefulness and stage 2 and rapid eye movement sleep. A computer-controlled ventilator delivered inspiratory pressures that varied randomly from breath to breath. Application of the model to the corresponding subject responses allowed the delineation of the three components of HRV. In all states, RCC gain was lower in OSAS patients than in normal subjects ( P < 0.04). ABR gain was also reduced in OSAS patients ( P < 0.03). RCC and ABR gains increased from wakefulness to sleep ( P < 0.04). However, there was no difference in PSR gain between subject groups or across states. The findings of this study suggest that the adverse autonomic effects of OSAS include impairment of baroreflex gain and central respiratory-cardiovascular coupling, but the component of respiratory sinus arrhythmia that is mediated by lung vagal feedback remains intact.
Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig
Authors: Kind Karen L. , Roberts Claire T. , Sohlstrom Annica I. , Katsman Arkadi , Clifton Peter M. , Robinson Jeffrey S. , Owens Julie A.
Published: October 2004

Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term ∼69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (−39%) and placental (−30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.
Antioxidant defense responses to sleep loss and sleep recovery
Authors: Everson Carol A. , Laatsch Christa D. , Hogg Neil
Published: October 2004

Sleep deprivation in humans is widely believed to impair health, and sleep is thought to have powerful restorative properties. The specific physical and biochemical factors and processes mediating these outcomes, however, are poorly elucidated. Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical abnormality. Metabolic and immunological consequences of sleep deprivation point to a high potential for antioxidant imbalance. The objective, therefore, was to study glutathione content in the liver, heart, and lung, because glutathione is considered a major free radical scavenger that reflects the degree to which a tissue has been oxidatively challenged. We also investigated major enzymatic antioxidants, including catalase and glutathione peroxidase, as well as indexes of glutathione recycling. Catalase activity and glutathione content, which normally are tightly regulated, were both decreased in liver by 23–36% by 5 and 10 days of sleep deprivation. Such levels are associated with impaired health in other animal models of oxidative stress-associated disease. The decreases were accompanied by markers of generalized cell injury and absence of responses by the other enzymatic antioxidants under study. Enzymatic activities in the heart indicated an increased rate of oxidative pentose phosphate pathway activity during sleep deprivation. Recovery sleep normalized antioxidant content in liver and enhanced enzymatic antioxidant activities in both the liver and the heart. The present results link uncompensated oxidative stress to health effects induced by sleep deprivation and provide evidence that restoration of antioxidant balance is a property of recovery sleep.
PDZ interactions and proximal tubular phosphate reabsorption
Authors: Biber Jürg , Gisler Serge M. , Hernando Nati , Wagner Carsten A. , Murer Heini
Published: October 2004

In adults, the extent of renal reabsorption of Pi and consequently the extent of urinary excretion of phosphate are to a large extent determined by the abundance of the Na-Pi cotransporter NaPi-IIa (SLC34A1). Localization of this cotransporter is restricted to the apical membrane of proximal tubular cells, and its abundance is controlled by a number of factors and pathophysiological conditions. To guarantee a proper apical localization and specific regulated endocytosis of NaPi-IIa, an orchestrated pattern of protein interactions has to be envisaged. Attempts to screen for such interacting proteins resulted in the identification of a PDZ domain containing proteins. The purpose of this review is to discuss the roles of these PDZ proteins in proximal tubular Na-Pi cotransport.
Comroe's study of aortic chemoreceptors: a path well chosen
Authors: Neubauer Judith A.
Published: October 2004

This essay looks at the historical significance of an APS classic paper that is freely available online

Comroe JH Jr. The location and function of the chemoreceptors of the aorta. Am J Physiol 127: 176—191, 1939 ( http://ajplegacy.physiology.org/cgi/reprint/127/1/176 ).
First electrodes for blood Po2 and Pco2 determination
Authors: Severinghaus John W.
Published: October 2004

This essay looks at the historical significance of an APS classic paper that is freely available online:

Severinghaus JW and Bradley AF. Electrodes for blood Po2 and Pco2 determination. J Appl Physiol 13: 515—520, 1958 ( http://jap.physiology.org/cgi/reprint/13/3/515 ).
Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs
Authors: Schwarte Lothar A. , Fournell Artur , van Bommel Jasper , Ince Can
Published: October 2004

Acute normovolemic hemodilution (ANH) compromizes intestinal microcirculatory oxygenation; however, the underlying mechanisms are incompletely understood. We hypothesized that contributors herein include redistribution of oxygen away from the intestines and shunting of oxygen within the intestines. The latter may be due to the impaired ability of erythrocytes to off-load oxygen within the microcirculation, thus yielding low tissue/plasma Po2 but elevated microcirculatory hemoglobin oxygen (HbO2) saturations. Alternatively, oxygen shunting may also be due to reduced erythrocyte deformability, hindering the ability of erythrocytes to enter capillaries. Anesthetized pigs underwent ANH (20, 40, 60, and 90 ml/kg hydroxyethyl starch; ANH group: n = 10; controls: n = 5). We measured systemic and mesenteric perfusion. Microvascular intestinal oxygenation was measured independently by remission spectrophotometry [microcirculatory HbO2 saturation (μHbO2)] and palladium-porphyrin phosphorescence quenching [microcirculatory oxygen pressure in plasma/tissue (μPo2)]. Microcirculatory oxygen shunting was assessed as the disparity between mucosal and mesenteric venous HbO2 saturation (HbO2-gap). Erythrocyte deformability was measured as shear stress-induced cell elongation (LORCA difractometer). ANH reduced hemoglobin concentration from 8.1 to 2.2 g/dl. Relative mesenteric perfusion decreased (decreased mesenteric/systemic perfusion fraction). A paralleled reduction occurred in mucosal μHbO2 (68 ± 2 to 41 ± 3%) and μPo2 (28 ± 1 to 17 ± 1 Torr). Thus the proposed constellation indicative for oxygen off-load deficits (sustained μHbO2 at decreased μPo2) did not develop. A twofold increase in the HbO2-gap indicated increasing intestinal microcirculatory oxygen shunting. Significant impairment in erythrocyte deformability developed during ANH. We conclude that reduced intestinal oxygenation during ANH is, in addition to redistribution of oxygen delivery away from the intestines, associated with oxygen shunting within the intestines. This shunting appears to be not primarily caused by oxygen off-load deficit but rather by oxygen/erythrocytes bypassing capillaries, wherein a potential contributor is impaired erythrocyte deformability.
Molecular Interactions Leading to Lipoprotein Retention and the Initiation of Atherosclerosis
Authors: Khalil Maged F. , Wagner William D. , Goldberg Ira J.
Published: October 2004

Atherosclerosis is distinguished by the accumulation of lipoprotein lipid within the arterial wall. An ionic interaction of positively charged regions of apolipoprotein (apo) B with matrix proteins, including proteoglycans, collagen, and fibronectin, is thought to initiate this process. Proteoglycans are complex glycoproteins containing highly negatively charged carbohydrate chains. These proteins are abundant in atherosclerosis lesions, and they associate with apoB-containing lipoproteins. Several specific regions of apoB may mediate this process. Other lipoprotein-associated proteins, including apoE and lipases, might also participate in this process. In addition, retention may occur via lipoprotein association with other matrix molecules or as a consequence of intra-arterial lipoprotein aggregation.
Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis
Authors: Stoll Lynn L. , Denning Gerene M. , Weintraub Neal L.
Published: October 2004

Atherosclerosis is increasingly recognized as a chronic inflammatory disease. Although a variety of inflammatory markers (ie, C-reactive protein) have been associated with atherosclerosis and its consequences, it is important to identify principal mediators of the inflammatory responses. One potentially important source of vascular inflammation in atherosclerosis is bacterial endotoxin. Mutations in Toll-like receptor 4 (TLR-4), an integral component of the endotoxin signaling complex, are fairly common in the Caucasian population and have recently been associated with reduced incidence of atherosclerosis and other cardiovascular diseases in some studies. Moreover, epidemiological studies suggest that endotoxemia at levels as low as 50 pg/mL constitutes a strong risk factor for the development of atherosclerosis. Endotoxin concentrations in this range may be produced by a variety of common subclinical Gram-negative infections. In this article, we outline the main elements of the endotoxin signaling receptor complex that initiates proinflammatory signaling (lipopolysaccharide binding protein [LBP], CD14, TLR-4, and MD-2) and discuss how changes in expression of these molecules may affect proatherogenic responses in the vessel wall. We also describe some of the proinflammatory effects of endotoxin that may be relevant to atherosclerosis, and discuss how serum lipoproteins, especially high-density lipoprotein, may modulate endotoxin-induced inflammatory responses. Further, we discuss recent findings suggesting that the lipid-lowering statins may have an additional protective role in blocking at least some of these proinflammatory signaling pathways. Finally, we discuss species diversity with regard to endotoxin signaling that should be considered when extrapolating experimental data from animal models to humans.
Disruption of Autosomal Recessive Hypercholesterolemia Gene Shows Different Phenotype In Vitro and In Vivo
Authors: Harada-Shiba Mariko , Takagi Atsuko , Marutsuka Kousuke , Moriguchi Sayaka , Yagyu Hiroaki , Ishibashi Shun , Asada Yujiro , Yokoyama Shinji
Published: October 2004

We previously characterized the patients with autosomal recessive hypercholesterolemia (ARH) as having severe hypercholesterolemia and retarded plasma low-density lipoprotein (LDL) clearance despite normal LDL receptor (LDLR) function in their cultured fibroblasts, and we identified a mutation in the
ARH
locus in these patients. ARH protein is an adaptor protein of the LDL and reportedly modulates its internalization. We developed ARH knockout mice (
ARH
−/−
) to study the function of this protein. Plasma total cholesterol level was higher in
ARH
−/−
mice than that in wild-type mice (
ARH
+/+
), being attributed to a 6-fold increase of LDL, whereas plasma lipoprotein was normal in the heterozygotes (
ARH
+/−
). Clearance of
125
I-LDL from plasma was retarded in
ARH
−/−
mice, as much as that found in
LDLR
−/−
mice. Fluorescence activity of the intravenously injected 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-LDL was recovered in the cytosol of the hepatocytes of
ARH
+/+
mice, but not in those of
ARH
−/−
or
LDLR
−/−
mice. Also, less radioactivity was recovered in the liver of
ARH
−/−
or
LDLR
−/−
mice when [
3
H]cholesteryl oleyl ether (CE)-labeled LDL was injected. In contrast, uptakes of [
3
H]CE-labeled LDL,
125
I-LDL, and DiI-LDL were all normal or slightly subnormal when the
ARH
−/−
hepatocytes were cultured. We thus concluded that the function of the hepatic LDLR is impaired in the
ARH
−/−
mice in vivo, despite its normal function in vitro. These findings were consistent with the observations with the ARH homozygous patients and suggested that certain cellular environmental factors modulate the requirement of ARH for the LDLR function.
Epoxycyclopentenone-Containing Oxidized Phospholipids Restore Endothelial Barrier Function via Cdc42 and Rac
Authors: Birukov Konstantin G. , Bochkov Valery N. , Birukova Anna A. , Kawkitinarong Kamon , Rios Alexander , Leitner Alexander , Verin Alexander D. , Bokoch Gary M. , Leitinger Norbert , Garcia Joe. G.N.
Published: October 2004

After an acute phase of inflammation or injury, restoration of the endothelial barrier is important to regain vascular integrity and to prevent edema formation. However, little is known about mediators that control restoration of endothelial barrier function. We show here that oxidized phospholipids that accumulate at sites of inflammation and tissue damage are potent regulators of endothelial barrier function. Oxygenated epoxyisoprostane-containing phospholipids, but not fragmented oxidized phospholipids, exhibited barrier-protective effects mediated by small GTPases Cdc42 and Rac and their cytoskeletal, focal adhesion, and adherens junction effector proteins. Oxidized phospholipid-induced cytoskeletal rearrangements resulted in a unique peripheral actin rim formation, which was mimicked by coexpression of constitutively active Cdc42 and Rac, and abolished by coexpression of dominant-negative Rac and Cdc42. Thus, oxidative modification of phospholipids during inflammation leads to the formation of novel regulators that may be critically involved in restoration of vascular barrier function.
Translation of Ischemic Preconditioning to the Patient
Authors: Ratan Rajiv R. , Siddiq Ambreena , Aminova Leila , Lange Philipp S. , Langley Brett , Ayoub Issam , Gensert JoAnn , Chavez Juan
Published: October 2004

Effective therapies for stroke must interdict multiple parallel and sequential pathophysiological events. A paradigm which offers insight into multivalent but thoughtfully coordinated protective programs is ischemic preconditioning. A central hypothesis of our group and others is that pharmacological agents that activate programs of gene expression normally induced by ischemic preconditioning will be effective agents for the prevention and treatment of stroke. Inhibitors of a class of enzymes, the hypoxia inducible factor-1 (HIF-1) prolyl hydroxylases stabilize the transcriptional activator HIF-1 and activate target genes involved in compensation for ischemia, including erythropoeitin (Epo) and vascular endothelial growth factor (VEGF). Here, we review evidence suggesting that the HIF-1 prolyl hyroxylases are inhibited during ischemic preconditioning and that pharmacological inhibitors of these enzymes are viable targets for stroke therapy.
Two Sodium/Calcium Exchanger Gene Products, NCX1 and NCX3, Play a Major Role in the Development of Permanent Focal Cerebral Ischemia
Authors: Pignataro Giuseppe , Gala Rosaria , Cuomo Ornella , Tortiglione Anna , Giaccio Lucia , Castaldo Pasqualina , Sirabella Rossana , Matrone Carmela , Canitano Adriana , Amoroso Salvatore , Di Renzo Gianfranco , Annunziato Lucio
Published: October 2004

Background and Purpose—

The Na
+
/Ca
2+
exchanger, by mediating Ca
2+
and Na
+
fluxes in a bidirectional way across the synaptic plasma membrane, may play a pivotal role in the events leading to anoxic damage. In the brain, there are 3 different genes coding for 3 different proteins: NCX1, NCX2, and NCX3. The aim of this study was to determine whether NCX1, NCX2, and NCX3 might play a differential role in the development of cerebral injury induced by permanent middle cerebral artery occlusion (pMCAO).

Methods—

By means of Western blotting, NCX1, NCX2, and NCX3 protein expression was evaluated in the ischemic core and in the remaining nonischemic area of the slice at different time intervals starting from ischemia induction. The role of each isoform was also assessed with antisense oligodeoxynucleotides (ODNs) targeted for each isoform. These ODNs were continuously intracerebroventricularly infused with an osmotic minipump (1 μL/h) for 48 hours, 24 hours before pMCAO.

Results—

The results showed that after pMCAO all 3 NCX proteins were downregulated in ischemic core; NCX3 decreased in periinfarctual area whereas NCX1 and NCX2 were unchanged. The ODNs for NCX1 and NCX3 gene products were capable of inducing an increase in the ischemic lesion and to worsen neurological scores.

Conclusions—

The results of this study suggest that in the neuroprotective effect exerted by NCX during ischemic injury, the major role is prevalently exerted by NCX1 and NCX3 gene products.
Enhanced Motor Cortex Excitability During Ipsilateral Voluntary Hand Activation in Healthy Subjects and Stroke Patients
Authors: Woldag Hartwig , Lukhaup Sven , Renner Caroline , Hummelsheim Horst
Published: October 2004

Background and Purpose—

It is still a matter of debate whether the ipsilateral voluntary hand activation has a facilitatory or inhibitory effect on the nondominant or affected hemisphere. To give an answer to this question is of great importance for the rehabilitation of stroke patients, because they often use the unaffected hand for compensation.

Methods—

Ten healthy volunteers and 11 stroke patients were investigated using transcranial magnetic stimulation (TMS). TMS was applied to the dominant/unaffected hemisphere during performance of different tasks (simple index finger abduction, pinch grip, and power grip) at various force levels (5%, 10%, 50%, and 100% maximal voluntary contraction) with the ipsilateral hand. Peak-to-peak amplitudes of motor-evoked potentials were used as measure for motor cortex excitability.

Results—

Both simple and complex tasks led to a facilitation of the contralateral corticospinal system at all levels of applied force. Not only the facilitatory effect in general but also the slope of the relationship between force level and MEP amplitude were significantly lower in stroke patients indicating that both the general activation level of the impaired motor system and the bandwidth of possible activation levels are diminished.

Conclusion—

Voluntary activation of the hand does not exert an inhibitory effect on the excitability of the ipsilateral hemisphere in healthy volunteers or in stroke patients.
Early Vasospasm on Admission Angiography in Patients with Aneurysmal Subarachnoid Hemorrhage Is a Predictor for In-Hospital Complications and Poor Outcome
Authors: Baldwin Maria E. , Macdonald R. Loch , Huo Dezheng , Novakovia Roberta L. , Goldenberg Fernando D. , Frank Jeffrey I. , Rosengart Axel J.
Published: October 2004

Background and Purpose—

Early vasospasm (EVSP), defined here as arterial narrowing seen on diagnostic angiography within the first 48 hours of aneurysmal rupture, is a rarely reported and poorly defined phenomenon in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to characterize EVSP in a large database of such patients.

Methods—

We analyzed the relationship of EVSP to clinical characteristics, in-hospital complications, and outcome at 3 months among 3478 patients entered into 4 prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997.

Results—

Three hundred thirty-nine (10%) of 3478 patients had EVSP. EVSP was significantly more likely in patients with poor neurological grade on admission, history of SAH, intracerebral hematoma, larger aneurysm, thick SAH on cranial computed tomography, and intraventricular hemorrhage. EVSP was not associated with delayed cerebral vasospasm. After adjustment for differences in admission characteristics, EVSP was associated with cerebral infarction (adjusted odds ratios [OR]=1.51; 95% CI, 1.18 to 1.94;
P
=0.001), neurological worsening (OR=1.41; 95% CI, 1.10 to 1.81;
P
=0.007), and unfavorable outcome (OR=1.51; 95% CI, 1.15 to 2.00;
P
=0.003). In addition, there was a trend for patients with increasingly severe EVSP to have unfavorable outcome (OR=1.84 for mild and OR=2.66 for moderate/severe EVSP).

Conclusions—

EVSP was seen in 10% of SAH patients and was predictive of cerebral infarction and neurological worsening as well as unfavorable outcome at 3 months. EVSP was not associated with late vasospasm. EVSP may be as important as delayed vasospasm in predicting complications and long-term morbidity in SAH patients.
Determination of Carotid Artery Atherosclerotic Lesion Type and Distribution in Hypercholesterolemic Patients With Moderate Carotid Stenosis Using Noninvasive Magnetic Resonance Imaging
Authors: Chu Baocheng , Hatsukami Thomas S. , Polissar Nayak L. , Zhao Xue-Qiao , Kraiss Lawrence W. , Parker Dennis L. , Waterton John C. , Raichlen Joel S. , Hamar Wendy , Yuan Chun
Published: October 2004

Background and Purpose—

The aims of this study were to noninvasively determine carotid atherosclerotic lesion type and distribution and to evaluate the reproducibility of determining lesion types in asymptomatic patients with moderate hypercholesterolemia and moderate carotid artery (CA) stenosis using MRI.

Methods—

Forty-two asymptomatic patients with moderate CA stenosis underwent bilateral carotid MRI in a 1.5-T scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MRI-modified American Heart Association criteria were used to evaluate lesion types at 3 locations (common and internal CA [CCA and ICA, respectively] and CA bifurcation) and at the minimum lumen area. Two identical MR scans were conducted to evaluate reproducibility of lesion types.

Results—

Lesion types were obtained from 230 locations. Type III (39%) occurred most commonly, followed by types IV–V (25%), I–II (20%), VI (12%), and VII (4%). Type III was more commonly distributed in the CCA (n=35, 39%) and ICA (n=32, 36%). Type IV–V was more commonly distributed in the CCA (n=24, 41%) and at the bifurcation (n=21, 36%). Forty-two lesions were available at the site of minimum lumen area: type III (33%), IV–V (33%), VI (29%), and VII (5%). There was good agreement of lesion types between both MRI scans (Cohen’s κ=0.73; 95% CI: 0.65 to 0.81).

Conclusions—

MRI can determine lesion types reproducibly as well as the distribution of lesions in hypercholesterolemic patients with moderate CA stenosis. A wide range of lesion types, including advanced lesions, were found in these patients.
Blood Vessel Function and Cognition in Elderly Patients With Atherosclerosis
Authors: Moser David J. , Hoth Karin F. , Robinson Robert G. , Paulsen Jane S. , Sinkey Christine A. , Benjamin Michelle L. , Schultz Susan K. , Haynes William G.
Published: October 2004

Background and Purpose—

Although a strong relationship has been established between vascular disease and cognitive decline, the current challenge is to identify vascular risk factors and mechanisms that are associated with cognitive function before the development of severe dysfunction (eg, vascular dementia). This study was conducted to determine the relationship between blood vessel function and cognition in elderly patients with atherosclerosis.

Methods—

Participants were 14 elderly individuals with atherosclerotic vascular disease, who had no history of stroke, cardiac surgery, or dementia diagnosis. Forearm blood flow was measured before and after brachial artery infusion of 3 vasoactive agents (verapamil, acetylcholine, nitroprusside), and these measures of vessel function were then correlated with neuropsychological performance (total scale score on the Repeatable Battery for the Assessment of Neuropsychological Status).

Results—

Positive correlations were found between neuropsychological performance and vasodilation in response to all 3 agents, with 2 reaching statistical significance (verapamil: ρ=0.78,
P
=0.001; nitroprusside: ρ=0.56,
P
=0.038) and the third showing a strong trend toward significance (acetylcholine: ρ=0.49,
P
=0.076). Correlations between neuropsychological performance and more conventional vascular-related variables were much weaker.

Conclusions—

These data provide preliminary evidence of a relationship between resistance vessel function and neuropsychological performance. With further research, measures of vessel dysfunction may be useful in identifying individuals at risk for cognitive decline and vascular dementia.
Improved Prediction of Final Infarct Volume Using Bolus Delay–Corrected Perfusion-Weighted MRI
Authors: Rose Stephen E. , Janke Andrew L. , Griffin Mark , Finnigan Simon , Chalk Jonathan B.
Published: October 2004

Background and Purpose—

Magnetic resonance imaging (MRI)-based perfusion measures using dynamic susceptibility contrast are extremely useful for identification of ischemic penumbral tissue in acute stroke. However, errors in the measurement of cerebral blood flow (CBF) and mean transit time (MTT) can occur. The aim of this study was to investigate whether bolus delay–corrected (BDC) perfusion measures enable better delineation of the ischemic penumbra.

Methods—

Diffusion-weighted MRI (DWI) and perfusion-weighted MRI data were acquired from 19 acute stroke patients. Perfusion abnormalities were manually defined on BDC perfusion maps (corrected MTT [cMTT] and corrected CBF [cCBF]), and on maps derived from an arterial input function placed within the contralateral (CBF, MTT) and ipsilateral (ipsilateral CBF [iCBF] and ipsilateral MTT [iMTT]) middle cerebral artery. Perfusion lesion volumes were correlated with 30-day T2-weighted MRI lesion volumes and with clinical outcome using the National Institutes of Health Stroke Scale (NIHSS).

Results—

Spearman correlation coefficients for comparing lesion volumes delineated on DWI, CBF, iCBF, cCBF, MTT, iMTT, and cMTT maps with 30-day T2-weighted lesion volumes were 0.72, 0.87, 0.88, 0.90, 0.84, 0.92, and 0.96, respectively (all
P
<0.001). The analogous correlation coefficients for comparing 30-day National Institutes of Health Stroke Scale (NIHSS) scores were 0.39 (NS), 0.69 (NS), 0.75 (
P
<0.001), 0.62 (NS), 0.72 (
P
<0.001), 0.78 (
P
<0.001), and 0.83 (
P
<0.001), respectively.

Conclusions—

Uncorrected perfusion lesion volumes overestimated the extent of ischemic injury. BDC perfusion measures (cMTT) correlated more accurately with final lesion volume and clinical outcome. Such measures offer an improved estimation of the final infarct size in acute stroke.
Relative Importance of Rehabilitation Therapy Characteristics on Functional Outcomes for Persons With Stroke
Authors: Bode Rita K. , Heinemann Allen W. , Semik Patrick , Mallinson Trudy
Published: October 2004

Background and Purpose—

The purpose of this study was to evaluate the relative importance of therapy focus, intensity, and length of stay on greater than expected functional gain, controlling for stroke severity.

Methods—

This observational study included 198 first-stroke patients who were recruited from 8 in-patient rehabilitation facilities and 5 subacute programs. Stroke severity (motor, sensory and cognitive impairment) at admission was measured using an instrument combining all 3 aspects; self-care, mobility, and cognitive status at admission and discharge were measured with the Functional Independence Measure. Time spent by physical, occupational, and speech-language therapists on function- and impairment-focused activities were used to compute therapy intensity by discipline and type of activity. Residual change scores, estimated by regressing discharge on admission functional status, were modeled using patient and therapy characteristics.

Results—

Controlling for the stroke severity, greater than expected gains in self-care were predicted by longer lengths of stay and more intensive function-focused occupational therapy, and greater than expected cognitive gains were predicted by longer stays alone. Predictors of residual change in mobility, however, differed by gender: greater than expected gains in mobility for men were predicted by longer lengths of stay and more intense function-focused physical therapy whereas, for women, they were predicted by stroke severity alone.

Conclusions—

Unlike previous studies using raw functional gains, therapies accounted for a significant proportion of the variance in residual functional change. The results support studies suggesting that both content and amount of therapy are important aspects.
Intracerebral Hemorrhage
Authors: Gong Ye , Hua Ya , Keep Richard F. , Hoff Julian T. , Xi Guohua
Published: October 2004

Background and Purpose—

Intracerebral hemorrhage (ICH) is mostly a disease of the elderly, but most current experimental ICH models have used young animals. Age is an important factor in other forms of brain injury, affecting microglia and astrocyte reactions and plasticity. Therefore, the present study investigated the effects of aging on brain injury after ICH.

Methods—

Young and aged (3 and 18 months old, respectively) male Sprague-Dawley rats received an intracerebral infusion of 100 μL autologous blood. Age-related changes in brain swelling, glial reaction, stress protein (heat shock proteins [HSPs] 27 and 32), and neurological deficits were examined.

Results—

Brain swelling was more severe in old rats compared with young rats at 3 days after ICH (
P
<0.05). There were also more severe neurological deficits in the older rats at 1 day after ICH, which persisted for the 4 weeks of monitoring (
P
<0.05). The older rats also had stronger microglial activation and a greater perihematomal induction of HSP-27 and HSP-32 (
P
<0.05). In contrast, there was a weaker astrocytic reaction to the hematoma.

Conclusions—

ICH causes more severe brain swelling and neurological deficits in old rats. Clarification of the mechanisms of brain injury after ICH in the aging brain should help develop new therapeutic strategies for hemorrhagic brain injury.
Knowledge-Based Economies, Organizations and the Sociocultural Regulation of Work
Authors: Casey Catherine
Published: October 2004

A predominant economic and managerial discourse drives imperatives for a ‘knowledge-based’ economy, now widely espoused by economic leaders in much of the developed world. Demands for ever-modernizing ef.ciencies, production growth and competitive advantage encourage heightened emphasis on knowledge-rich production and innovation. They stimulate strategic managerial and organizational contingencies, labour market .exibility and deregulated markets, and weaken existing norms and processes in the social regulation of work. At the same time, political calls for a ‘learning society’ or a ‘knowledge society’ to accompany a knowledge-based economy gain much attention. They include demands for lifelong learning, for learning organizations and greater worker learning and skills development at work. This article critically examines the knowledge-based economy discourse and its formulation of worker and organizational learning. It argues that alternative conceptualizations of organizational learning that recognize workers’ cultural and non-material demands may stimulate resources for culturally innovative practices. In particular, the article considers ways in which learning economy discourses may be strategically utilized by trade unions, worker educators and other workplace actors in a revitalization of the sociocultural regulation of work.
Information Needs of Adolescents With Cancer
Authors: Decker Carol , Phillips Celeste R. , Haase Joan E.
Published: October 2004

Adolescents with cancer (AWC) have poorer treatment outcomes as well as higher incidence and mortality rates than do younger children, and they face additional challenges related to normal developmental issues of adolescence. Although research has shown that information on the cancer experience improves outcomes by decreasing uncertainty and increasing perceived support, little is known about the types of information AWC need and want. This study describes how AWC rate the importance of specific cancer-related information, analyzes gender and age group differences, and compares 2 different time-since-diagnosis groups of AWC. The sample consisted of adolescents with newly diagnosed cancer (n = 74) and those 1 to 3 years from diagnosis (n = 39). The Information Preferences of Adolescents (IPA) Scale was used to measure the adolescents’ information needs. Both samples of AWC rated the need for information as high. There were no significant differences by age, but females had significantly higher total scores for both groups and for many item means in the newly diagnosed group. Qualitative analysis of the additional write-in items generated 4 themes: treatment/side effects, uncertainty, social issues, and personal/emotional issues.
Neuropathic Pain in Children With Cancer
Authors: Jacob Eufemia
Published: October 2004

Different mechanisms of cancer pain may involve somatic, visceral, and neural tissues. Pain that involves the neural tissues is classified as neuropathic pain and is less responsive to analgesics than pain that involves somatic and visceral tissues. Because young children are unable to describe the quality of pain, presence of neuropathic pain with cancer may be unrecognized and undetected. The purpose of this article is to explain the nature of neuropathic pain, to review the literature related to children with cancer that suggests the presence of neuropathic pain, to outline assessment strategies that may lead to appropriate detection of neuropathic pain in children, and to discuss challenges in the management of neuropathic pain. Future research is needed to characterize the intensity, location, quality, and duration of neuropathic pain in children. In addition, research that would determine the efficacy of opioids, nonsteroidal anti-inflammatory drugs, and adjuvant analgesics (antidepressants, anticonvulsants) is needed to increase the nurses’ ability to assess and manage neuropathic pain in children with cancer.
Nurses’ Perceptions of Phase I Clinical Trials in Pediatric Oncology: A Review of the Literature
Authors: Chang Ann
Published: October 2004

A review of literature was conducted to explore nurses’ perceptions of phase I clinical trials in pediatric oncology. Specifically, nurses’ perceptions of the goals and outcomes, the nurse’s role, and the informed consent process in pediatric oncology phase I clinical trials were investigated. Findings on possible factors influencing the nurses’ perceptions and the quality of work-life of nurses working at pediatric phase I clinical trial centers were also searched. However, despite an extensive review of published works, no studies on nurses’ perceptions of phase I trials in pediatric oncology were found. Therefore, this literature review consists of findings in similar or related studies such as nurses’ perceptions of experimental therapies in the adult setting, adult patients’ perceptions, parents’ perceptions, or oncologists’perceptions of phase I clinical trials.
Mothers in Two Types of Lesbian Families: Stigma Experiences, Supports, and Burdens
Authors: van Dam Mary Ann A.
Published: October 2004

This study of 360 lesbian mothers represented 180 dual-parent lesbian families from 38 U.S. states and examined the maternal experiences with stigma and the families’ support systems and burdens. Mothers in lesbian families, who established a lesbian relationship and subsequently had children together, were compared to mothers in lesbian stepfamilies, where partners started their intimate relationship after having children. Results indicated that mothers in lesbian stepfamilies had less support. Both types of families had men in their lives, and most mothers were burdened by concerns regarding their children’s experience of stigma. Both types of families experience stigma; however, mothers in lesbian stepfamilies perceive more stigma. Health care providers (HCP) should know the tolerance for lesbian identities in their community and assist women in disclosing their family constellation. Specific suggestions are provided for the HCP to make these assessments.
A Bold Leadership Style: Nothing Will Ever Be Accomplished If All Obstacles Must First Be Overcome!
Authors: Fitzpatrick Joyce J.
Published: October 2004

A bold and visionary leader, Joyce J. Fitzpatrick charts her leadership style. Seven key components of her leadership style are included: vision and insight, positive thinking and behavior, creating win-win situations, learning from mistakes, sensitivity to others, sharpening the leadership skill set, and mentoring. Examples of her pioneering leadership in nursing and health care are included.