bluuebunny/crossref_metadata_2025 huggingface dataset:
Planning for Family and Financial Success in Family Businesses
Authors: Sorenson Ritch L.
Published: April 2004

Deane Kanaly has observed the success and failure of hundreds of family businesses; he knows what makes family businesses work. He also knows how to plan for financial success. In this interview, he provides insights and suggestions that should be of value to consultants, educators, and business owners. Kanaly's comments get to the heart of a variety of issues, including family relationships, financial planning, estate planning, and successful entrepreneurship in family businesses.
Entrepreneurship as Radical Change in the Family Business: Exploring the Role of Cultural Patterns
Authors: Hall Annika , Melin Leif , Nordqvist Mattias
Published: April 2004

This article explores the relationship between organizational culture and the entrepreneurial process that is viewed as radical change in the context of the family business. Drawing on results from two in-depth family business case studies, the authors develop a conceptual model for understanding organizational culture and its impact on entrepreneurial activities. The model is built around the extent to which the culture is connected to one dominant family member or several family members, the degree of cultural explicitness, and the degree of cultural openness. It is argued that whereas some cultural patterns tend to preserve the traditional way of doing business, others tend to facilitate entrepreneurial change. The conclusion is that to support entrepreneurial processes, managers need to foster a process of high-order learning in which old cultural patterns are continuously questioned and changed. To accomplish this, the organizational culture needs to be highly explicit and open.
Next-Generation Entrepreneurs and Succession: An Exploratory Study of Modes and Means of Managing Social Capital
Authors: Steier Lloyd
Published: April 2004

Relationships and connectivity play an enhanced role in most models of the new economy. For many firms, strategic advantage resides in the social capital (or relational wealth) they are able to nourish and maintain. This important asset is accumulated over time and not easily traded or transferred. For family firms with long-term continuity goals, the transfer and management of this largely intangible asset are a most significant activity. This research is based on interviews of next-generation entrepreneurs in 18 different firms. It contributes to the family business and more general management literature by identifying different ways in which relational wealth is transferred, created, and managed. Four different modes of transferring social capital emerged from the data: unplanned, sudden succession; rushed succession; natural immersion; and planned succession and deliberate transfer of social capital. Additionally, seven means of managing social capital emerged: deciphering existing network structures, deciphering the transactional content of network relationships, determining criticalities, attaining legitimacy, clarifying optimal role, managing ties through delegation and division of labor, and striving for optimal network configuration and reconstituting network structure and content. This paper concludes with a series of propositions for further research.
Work-Family Conflict: A Study of American and Australian Family Businesses
Authors: Smyrnios Kosmas X. , Romano Claudio A. , Tanewski George A. , Karofsky Paul I. , Millen Robert , Yilmaz Mustafa R.
Published: April 2004

This study examines causal pathways linking work strain to anxiety among Australian and American family business owners. To date, there has been no empirical test of strain-based, work-family conflict models on family businesses; nor have there been comparisons made between Australian and American business owners. This paper suggests a specific causal model and provides country-specific and comparative evidence for that model. The suggested model includes mediation and moderation mechanisms that link work strain and anxiety from the perspective of business owners. Data for the research were obtained through the administration of essentially identical questionnaires in the two countries in 1999. Results show that the proposed model fits the data reasonably well, regardless of the type of firm and country.
Correlation of local and global orientation and spatial frequency tuning in macaque V1
Authors: Xing Dajun , Ringach Dario L. , Shapley Robert , Hawken Michael J
Published: April 2004

Visual cortical neurones display a variety of visual properties. Among those that emerge in the primary visual cortex V1 are sharpening of selectivity for spatial frequency and for orientation. The selectivity for these stimulus attributes can be measured around the peak of the tuning function, usually as bandwidth. Other selectivity measures take into account the response across a broader range of stimulus values. An example of such a global measure is the circular variance of orientation tuning. Here we introduce a similar measure in the spatial frequency domain that takes into account the shape of the tuning curve at frequencies lower than the peak, called the low‐spatial frequency variance. Our recent studies with dynamic stimuli suggest that the selectivity for spatial frequency and orientation is strongly correlated with the degree of suppression at low spatial frequencies and off‐axis orientations. Here we extend the study of the global tuning to stimulus conditions that measure the response of cells to the presentation of drifting sinusoidal grating stimuli for periods of a few seconds. We find that under such steady‐state stimulus conditions there is a strong correlation between the global selectivity measures, orientation circular variance and low spatial frequency variance. Consistent with previous studies, there is a weaker correlation between the local tuning measures, orientation and spatial frequency bandwidth. These results support the idea that there are multiple factors that contribute to tuning and that suppression observed in dynamic experiments is also likely to contribute to the global selectivity for steady‐state stimuli.
Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps
Authors: Kockskämper Jens , Ahmmed Gias U. , Zima Aleksey V. , Sheehan Katherine A. , Glitsch Helfried G. , Blatter Lothar A.
Published: April 2004

Palytoxin is a coral toxin that seriously impairs heart function, but its effects on excitation-contraction (E-C) coupling have remained elusive. Therefore, we studied the effects of palytoxin on mechanisms involved in atrial E-C coupling. In field-stimulated cat atrial myocytes, palytoxin caused elevation of diastolic intracellular Ca2+ concentration ([Ca2+]i), a decrease in [Ca2+]i transient amplitude, Ca2+ alternans followed by [Ca2+]i waves, and failures of Ca2+ release. The decrease in [Ca2+]i transient amplitude occurred despite high sarcoplasmic reticulum (SR) Ca2+ load. In voltage-clamped myocytes, palytoxin induced a current with a linear current-voltage relationship (reversal potential ∼5 mV) that was blocked by ouabain. Whole cell Ca2+ current and ryanodine receptor Ca2+ release channel function remained unaffected by the toxin. However, palytoxin significantly reduced Ca2+ pumping of isolated SR vesicles. In current-clamped myocytes stimulated at 1 Hz, palytoxin induced a depolarization of the resting membrane potential that was accompanied by delayed afterdepolarizations. No major changes of action potential configuration were observed. The results demonstrate that palytoxin interferes with the function of the sarcolemmal Na+-K+ pump and the SR Ca2+ pump. The suggested mode of palytoxin toxicity in the atrium involves the conversion of Na+-K+ pumps into nonselective cation channels as a primary event followed by depolarization, Na+ accumulation, and Ca2+ overload, which, in turn, causes arrhythmogenic [Ca2+]i waves and delayed afterdepolarizations.
Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species
Authors: Uchikura Keiichiro , Wada Tatehiko , Hoshino Sumito , Nagakawa Yuichi , Aiko Takashi , Bulkley Gregory B. , Klein Andrew S. , Sun Zhaoli
Published: April 2004

Fas-Fas ligand (FasL)-dependent pathways exert a suppressive effect on inflammatory responses in immune-privileged organs. FasL expression in hepatic Kupffer cells (KC) has been implicated in hepatic immunoregulation. In this study, modulation of FasL expression of KC by endogenous gut-derived bacterial LPS and the role of reactive oxygen species (ROS) as potential mediators of FasL expression in KC were investigated. LPS stimulation of KC resulted in upstream ROS generation and, subsequently, increased FasL expression and consequent Jurkat cell (Fas-positive) apoptosis. The NADPH oxidase and xanthine oxidase enzymatic pathways appear to be major sources of this upstream ROS generation. Increased FasL expression was blocked by antioxidants and by enzymatic blocking of ROS generation. Exogenous administration of H2O2stimulated KC FasL expression and subsequent Jurkat cell apoptosis. Intracellular endogenous ROS generation may therefore represent an important signal transduction pathway for FasL expression in KC.
Gender differences in ANG II levels and action on multiple K+current modulation pathways in diabetic rats
Authors: Shimoni Yakhin , Liu Xiu-Fang
Published: April 2004

Gender differences were studied in ventricular myocytes from insulin-deficient (Type 1) diabetic rats. Cells were obtained by enzymatic dispersion of hearts from control male and female rats and from rats made diabetic with streptozotocin (100 mg/kg) 7–14 days before experiments. ANG II content, measured by ELISA, was augmented in diabetic males but unaltered in diabetic females. In diabetic ovariectomized females, ANG II levels were augmented as in males. ANG II affects multiple cellular pathways including activation of protein kinase C (PKC) and several tyrosine kinases as well as inhibition of protein kinase A (PKA). The involvement of these pathways in modulating outward K+currents was studied. Transient and sustained outward K+currents were measured using the whole cell voltage-clamp method. In males, these currents are attenuated under diabetic conditions but are augmented by the ANG II-converting enzyme inhibitor quinapril. Activation of PKA by 8-bromo-cAMP enhanced both K+currents in cells from diabetic males. The augmentation of these currents by quinapril was blocked when PKA inhibition was maintained with the Rp isomer of 3′,5′-cyclic monophosphorothioate. Inhibition of tyrosine kinases by genistein also augmented K+currents in cells from diabetic males. Action potentials were abbreviated by 8-bromo-cAMP and genistein. However, both genistein and 8-bromo-cAMP had no effect on K+currents in cells from diabetic females. In cells from ovariectomized diabetic females, 8-bromo-cAMP and genistein enhanced these K+currents as in males. Inhibition of PKC augmented the transient and sustained K+currents in cells from diabetic males and females. A contribution of non-ANG II-dependent activation of PKC is suggested. These results describe some of the mechanisms that may underlie gender-specific differences in the development of cardiac disease and arrhythmias.
Activation of the apical Na+/H+exchanger NHE3 by formate: a basis of enhanced fluid and electrolyte reabsorption by formate in the kidney
Authors: Petrovic Snezana , Barone Sharon , Weinstein Alan M. , Soleimani Manoocher
Published: April 2004

Formate stimulates sodium chloride and fluid reabsorption in kidney proximal tubule; however, the exact cellular mechanism of this effect remains unknown. We hypothesized that the primary target of formate is the apical Na+/H+exchanger. Here, we demonstrate that formate directly enhances the apical Na+/H+exchanger (NHE3) activity in mouse kidney proximal tubule. In the absence of CO2/HCO3−, addition of formate (500 μM) to the bath and lumen of microperfused mouse kidney proximal tubule caused significant intracellular alkalinization, with intracellular pH (pHi) increasing from baseline levels 7.17 ± 0.01 to 7.55 ± 0.01 ( P < 0.001, n = 14), with a ΔpH of 0.38 ± 0.02. Removal of luminal chloride did not block cell pH alkalinization by formate (baseline pH of 7.26 ± 0.01 to 7.53 ± 0.01 with formate, P < 0.001, n = 10), indicating that the apical Cl−/OH−exchanger was not the primary mediator of the effect of formate on cell pH. However, removal of sodium from the lumen or addition of EIPA completely prevented cell pH alkalinization. Addition of formate to the lumen and bath in the outer medullary collecting duct, which does not express any apical Na+/H+exchanger, did not cause any cell pH alkalinization. At lower concentrations (50 μM), formate caused significant pHialkalinization in proximal tubule cells, with pHiincreasing from baseline levels 7.15 ± 0.02 to 7.36 ± 0.02 ( P < 0.02, n = 11). Acetate, at 50 μM, had no effect on pHi. Formate’s effect was observed both in the absence and presence of CO2/HCO3−in the media. We conclude that formate stimulates the apical Na+/H+exchanger NHE3 in the kidney proximal tubule. We propose that formate stimulation of chloride reabsorption in the proximal tubule is indirect and is secondary to the activation of apical Na+/H+exchanger NHE3, which then leads to the stimulation of the apical chloride/base exchanger.
Evidence of a myogenic response in vasomotor control of forearm and palm cutaneous microcirculations
Authors: Durand S. , Zhang R. , Cui J. , Wilson T. E. , Crandall C. G.
Published: April 2004

Previous investigations of autoregulatory mechanisms in the control of skin blood flow suffer from the possibility of interfering effects of the autonomic nervous system. To address this question, in 11 subjects cutaneous vascular responses were measured during acute changes in perfusion pressure (using Valsalva maneuver; VM) before and after ganglionic blockade via systemic trimethaphan infusion. Cutaneous vascular conductance at baseline (CVCbase) and during the last 5 s of the VM (CVCVM) were measured from forearm (nonglabrous) and palm (glabrous) skin. During the VM without ganglionic blockade, compared with CVCbase, CVCVM decreased significantly at the palm [0.79 ± 0.17 to 0.55 ± 0.17 arbitrary units (AU)/mmHg; P = 0.002] but was unchanged at the forearm (0.13 ± 0.02 to 0.16 ± 0.02 AU/mmHg; P = 0.50). After ganglionic blockade, VM induced pronounced decreases in perfusion pressure, which resulted in significant increases in CVCVM at both forearm (0.19 ± 0.03 to 0.31 ± 0.07 AU/mmHg; P = 0.008) and palm (1.84 ± 0.29 to 2.76 ± 0.63 AU/mmHg; P = 0.003) sites. These results suggest that, devoid of autonomic control, both glabrous and nonglabrous skin are capable of exhibiting vasomotor autoregulation during pronounced reductions in perfusion pressure.
Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats
Authors: MacLennan Nicole K. , James S. Jill , Melnyk Stephan , Piroozi Ali , Jernigan Stefanie , Hsu Jennifer L. , Janke Sara M. , Pham Tho D. , Lane Robert H.
Published: April 2004

Uteroplacental insufficiency leads to intrauterine growth retardation (IUGR) and increases the risk of insulin resistance and hypertriglyceridemia in both humans and rats. Postnatal changes in hepatic gene expression characterize the postnatal IUGR rat, despite the transient nature of the initial in utero insult. Phenomena such as DNA methylation and histone acetylation can induce a relatively static reprogramming of gene transcription by altering chromatin infrastructure. We therefore hypothesized that uteroplacental insufficiency persistently affects DNA methylation and histone acetylation in the IUGR rat liver. IUGR rat pups were created by inducing uteroplacental insufficiency through bilateral uterine artery ligation of the pregnant dam on day 19 of gestation. The SssI methyltransferase assay and two-dimensional thin-layer chromatography demonstrated genome-wide DNA hypomethylation in postnatal IUGR liver. To investigate a possible mechanism for this hypomethylation, levels of hepatic metabolites and enzyme mRNAs involved in one-carbon metabolism were measured using HPLC with coulometric electrochemical detection and real-time RT-PCR, respectively. Uteroplacental insufficiency increased IUGR levels of S-adenosylhomocysteine, homocysteine, and methionine in association with decreased mRNA levels of methionine adenosyltransferase and cystathionine-β-synthase. Western blotting further demonstrated that increased quantities of acetylated histone H3 also characterized the IUGR liver. Increased hepatic levels of S-adenosylhomocysteine can promote DNA hypomethylation, which is often associated with histone hyperacetylation. We speculate that the altered intrauterine milieu associated with uteroplacental insufficiency affects hepatic one-carbon metabolism and subsequent DNA methylation, which thereby alters chromatin dynamics and leads to persistent changes in hepatic gene expression.
Adiponectin Specifically Increased Tissue Inhibitor of Metalloproteinase-1 Through Interleukin-10 Expression in Human Macrophages
Authors: Kumada Masahiro , Kihara Shinji , Ouchi Noriyuki , Kobayashi Hideki , Okamoto Yoshihisa , Ohashi Koji , Maeda Kazuhisa , Nagaretani Hiroyuki , Kishida Ken , Maeda Norikazu , Nagasawa Azumi , Funahashi Tohru , Matsuzawa Yuji
Published: April 2004

Background—

Vascular inflammation and subsequent matrix degradation play an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipose-specific plasma protein, accumulated to the injured artery and attenuated vascular inflammatory response. Clinically, high plasma adiponectin level was associated with low cardiovascular event rate in patients with chronic renal failure. The present study was designed to elucidate the effects of adiponectin on matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in human monocyte-derived macrophages.

Methods and Results—

Human monocyte-derived macrophages were incubated with the physiological concentrations of human recombinant adiponectin for the time indicated. Adiponectin treatment dose-dependently increased TIMP-1 mRNA levels without affecting MMP-9 mRNA levels. Adiponectin also augmented TIMP-1 secretion into the media, whereas MMP-9 secretion and activity were unchanged. Time course experiments indicated that TIMP-1 mRNA levels started to increase at 24 hours of adiponectin treatment and were significantly elevated at 48 hours. Adiponectin significantly increased interleukin-10 (IL-10) mRNA expression at the transcriptional level within 6 hours and significantly increased IL-10 protein secretion within 24 hours. Cotreatment of adiponectin with anti–IL-10 monoclonal antibody completely abolished adiponectin-induced TIMP-1 mRNA expression.

Conclusions—

Adiponectin selectively increased TIMP-1 expression in human monocyte-derived macrophages through IL-10 induction. This study identified, for the first time, the adiponectin/IL-10 interaction against vascular inflammation.
Bradykinin B
1
Receptor Expression Induced by Tissue Damage in the Rat Portal Vein
Authors: Medeiros Rodrigo , Cabrini Daniela A. , Ferreira Juliano , Fernandes Elizabeth S. , Mori Marcelo A.S. , Pesquero João B. , Bader Michael , Avellar Maria C.W. , Campos Maria M. , Calixto João B.
Published: April 2004

The bradykinin B
1
receptor (B
1
R) is normally absent under physiological conditions, but is highly inducible during inflammatory conditions or following tissue damage. The present study attempted to determine some of the mechanisms underlying B
1
R upregulation following tissue injury in rat portal vein. Damage induced by tissue isolation and in vitro incubation caused a significant and time-dependent increase in des-Arg
9
–bradykinin (des-Arg
9
–BK) responsiveness that paralleled the B
1
R mRNA expression, as confirmed by real-time quantitative PCR. In vitro incubation of rat portal vein also induced the activation of some members of the mitogen activated protein kinase (MAPK) family, namely, extracellular signal-regulated kinase (ERK), c-Jun NH
2
-terminal kinase (JNK), and p38 MAPK, an effect accompanied by degradation of the inhibitory protein IκBα and translocation of nuclear transcription factor-κB (NF-κB) to the nucleus. The blockade of p38 MAPK, JNK or NF-κB, but not ERK pathways with selective inhibitors, resulted in a significant reduction of the upregulated contractile response caused by the selective B
1
R agonist des-Arg
9
–BK, and largely prevented the induction of B
1
R mRNA expression in the rat portal vein. Together, these results demonstrate that in vitro tissue damage induces activation of several intracellular signaling pathways that have a key role in the control of B
1
R expression. B
1
R could exert a pivotal role in the development of the cardiovascular response associated with vascular damage.
Direct Observation of the Human Cerebral Microcirculation During Aneurysm Surgery Reveals Increased Arteriolar Contractility
Authors: Pennings Frederik A. , Bouma Gerrit J. , Ince Can
Published: April 2004

Background and Purpose—

The effects of aneurysmal subarachnoid hemorrhage on morphology and function of the cerebral microcirculation are poorly defined, partly due to the lack of suitable techniques to visualize the microvessels in vivo. We used orthogonal polarization spectral (OPS) imaging on the brain cortex during aneurysm surgery to directly observe the small cortical blood vessels and quantify their responses to hypocapnia.

Methods—

In 16 patients undergoing aneurysm surgery, the diameter changes of small cortical vessels (15 to 180 μm) were observed using OPS imaging. Ten patients were operated on early (within 48 hours after bleeding) and 6 underwent late surgery. Immediately after dura opening, the response to hyperventilation of arterioles and venules was observed with OPS imaging under sevoflurane anesthesia.

Results—

In patients operated on early, layers of subarachnoid blood were clearly visible. In this group, hyperventilation resulted in a 39±15% decrease in arteriolar diameter with a “bead-string” constriction pattern occurring in 60% of patients. In late surgery and in controls, no subarachnoid blood was seen. The arteriolar diameter decrease with hyperventilation was 17±20% in patients undergoing late surgery and 7±7% in controls. Venules were not affected by hyperventilation in any of the groups studied.

Conclusions—

OPS imaging allows direct in vivo observation of the cerebral microcirculation enabling us, for the first time, to visually observe and quantify microvascular reactivity in the human brain. The present study demonstrates increased contractile responses of the cerebral arterioles in the presence of subarachnoid blood, suggesting increased microvascular tonus with possibly greater susceptibility to ischemia.
A Biomechanical Comparison of Initial Soft Tissue Tibial Fixation Devices
Authors: Caborn David N. M. , Brand Jeff C. , Nyland John , Kocabey Yavuz
Published: April 2004

Background

Biomechanical testing of the Intrafix device has not been performed using human tibiae.

Hypothesis

The Intrafix device would provide comparable or superior tibial fixation of a quadrupled hamstring tendon graft to a 35-mm-long bioabsorbable interference screw.

Study Design

In vitro, biomechanical study.

Methods

Eight paired human tibiae and 16 quadrupled hamstring tendon grafts were divided into 2 groups. Each quadrupled hamstring tendon graft was fixed in a tunnel sized to 0.5 mm graft diameter with either an Intrafix device or a screw.

Results

Displacement at failure was greater in the Intrafix group (17.3 ± 4.6 mm versus 10.9 ± 4.4 mm, P = .002). Load at failure (796 ± 193 N versus 647 ± 269 N), stiffness (49.2 ± 21.9 N/mm versus 64.5 ± 22 N/mm), and bone mineral density (0.74 ±0.15 gm/cm3 versus 0.74 ± 0.14 gm/cm3) did not display significant differences for the Intrafix device and the screw, respectively (P > .05).

Conclusions

Displacement at failure was greater for the Intrafix device.

Clinical Relevance

Increased displacement at failure for the Intrafix group suggests slippage from sheath channel deployment. Concentric fixation may not occur when less than optimal tibial bone mineral density increases the difficulty of attaining precise sheath deployment and quadrupled hamstring tendon graft strand alignment.
Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis
Authors: Wagner Wolfgang , Ansorge Alexandra , Wirkner Ute , Eckstein Volker , Schwager Christian , Blake Jonathon , Miesala Katrin , Selig Jan , Saffrich Rainer , Ansorge Wilhelm , Ho Anthony D.
Published: April 2004

The molecular mechanisms that regulate asymmetric divisions of hematopoietic progenitor cells (HPCs) are not yet understood. The slow-dividing fraction (SDF) of HPCs is associated with primitive function and self-renewal, whereas the fast-dividing fraction (FDF) predominantly proceeds to differentiation. CD34+/CD38– cells of human umbilical cord blood were separated into the SDF and FDF. Genomewide gene expression analysis of these populations was determined using the newly developed Human Transcriptome Microarray containing 51 145 cDNA clones of the Unigene Set-RZPD3. In addition, gene expression profiles of CD34+/CD38– cells were compared with those of CD34+/CD38+ cells. Among the genes showing the highest expression levels in the SDF were the following: CD133, ERG, cyclin G2, MDR1, osteopontin, CLQR1, IFI16, JAK3, FZD6, and HOXA9, a pattern compatible with their primitive function and self-renewal capacity. Furthermore, morphologic differences between the SDF and FDF were determined. Cells in the SDF have more membrane protrusions and CD133 is located on these lamellipodia. The majority of cells in the SDF are rhodamine-123dull. These results provide molecular evidence that the SDF is associated with primitive function and serves as basis for a detailed understanding of asymmetric division of stem cells.
Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation
Authors: de Lima Marcos , Anagnostopoulos Athanasios , Munsell Mark , Shahjahan Munir , Ueno Naoto , Ippoliti Cindy , Andersson Borje S. , Gajewski James , Couriel Daniel , Cortes Jorge , Donato Michele , Neumann Joyce , Champlin Richard , Giralt Sergio
Published: April 2004

Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P = .006), patients in first CR (28% versus 3%, P = .008), and HLA-matched sibling donors (81% versus 40%, P = .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P = .036), and lower cumulative incidence of relapse-related mortality (P = .029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.
Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation
Authors: Offman Judith , Opelz Gerhard , Doehler Bernd , Cummins David , Halil Ozay , Banner Nicholas R. , Burke Margaret M. , Sullivan Dianne , Macpherson Peter , Karran Peter
Published: April 2004

Immunosuppression after organ transplantation is an acknowledged risk factor for skin cancer and lymphoma. We examined whether there was also an excess of leukemia in patients after transplantation and whether this might be related to a particular immunosuppressive treatment. Data from more than 170 000 patients indicated that organ transplantation is associated with a significantly increased risk for acute myeloid leukemia (AML). AML was more frequent after heart transplantation and lung transplantation than after kidney transplantation and was associated with immunosuppression by azathioprine, a thiopurine prodrug. Cellular resistance to thiopurines is associated with DNA mismatch repair (MMR) deficiency. We demonstrate that thiopurine treatment of human cells in vitro selects variants with defective MMR. Consistent with a similar selection in patient bone marrow, in 7 of 7 patients, transplant-related AML/myelodysplastic syndrome (MDS) exhibited the microsatellite instability (MSI) that is diagnostic for defective MMR. Because MSI occurs infrequently in de novo AML, we conclude that the selective proliferation of MMR-defective, azathioprine-resistant myeloid cells may contribute significantly to the development of AML/MDS in patients who have received organ transplants. Identifying azathioprine as a risk factor for AML/MDS suggests that discontinuing the use of azathioprine as an immunosuppressant might reduce the incidence of posttransplantation AML/MDS.
Managing Capacity Through Reward Programs
Authors: Kim Byung-Do , Shi Mengze , Srinivasan Kannan
Published: April 2004

Rewarding customers with own products or services has become an increasingly popular practice across a spectrum of industries such as airlines, hotels, and telecommunication. In these service industries, firms face demand uncertainty and strict short-term capacity constraint. When the market demand is low, firms hold excess capacities that would lead to intense price competition. In this paper we study the adoption and design of reward programs in the context of capacity management. We demonstrate that it is optimal for firms to offer capacity rewards when the market demand varies from one period to the other. By offering the reward programs, firms can effectively reduce available capacities when the market demand is low, and hence credibly show their unwillingness to undersell. Such a commitment can encourage their competitors to set their prices high. When firms provide reward programs, if a firm sets a higher price than the other and sells less today, in the future the firm can benefit from the other firm's larger reduction in available capacity through rewards. Thus, reward programs also provide additional incentives for firms to set higher current prices. Finally, since reward programs can add flexibility in adjusting the available capacities to the market demand, firms increase the size of regular capacities with reward programs.
Doing the Right Thing or Doing the Thing Right: Allocating Resources Between Marketing Research and Manufacturing
Authors: Hess James D. , Lucas Marilyn T.
Published: April 2004

Matching production with sales potential is essential for survival in volatile markets. Manufacturing and marketing managers compete for staff, space, cash, and other assets as they struggle both to determine what and how many products ought to be produced, and to actually produce them. We develop an analytical framework to answer one simple question, “How much marketing research should a firm do when it takes resources away from manufacturing the goods that generate revenue?” To understand the costs and benefits of marketing research, we account for the lost opportunities to produce these goods. Some analytical findings are striking: firms without initial knowledge of their potential customers should allocate one-third of the firm's resources to marketing research. The model suggests a host of issues to be more deeply studied by management scientists.
Extended-Interval Aminoglycoside Dosing for Treatment of Enterococcal and Staphylococcal Osteomyelitis
Authors: Graham A Christie , Mercier Renee-Claude , Achusim Louis E , Pai Manjunath P
Published: April 2004

BACKGROUND:

Gram-positive osteomyelitis requires long-term antibiotic therapy, much of which is often administered in the outpatient setting. Historically, synergistic aminoglycoside use in these infections requires multiple daily doses, which can be inconvenient. Data regarding extended-interval aminoglycoside dosing (EIAD), also known as once-daily dosing, in this setting are lacking.

OBJECTIVE:

To evaluate the safety and efficacy of EIAD in the treatment of gram-positive osteomyelitis.

METHODS:

Retrospective chart review of adult patients treated for documented, gram-positive osteomyelitis with EIAD at the University of New Mexico Home IV Antibiotic Clinic was conducted. The patients' medical records were reviewed by an infectious diseases clinical pharmacist. Clinical and microbiologic outcomes and the incidence of nephrotoxicity and ototoxicity were the main outcome measures.

RESULTS:

Fifteen patients (16 events) were included. Enterococcus spp. was the most common organism isolated. Nine patients had infected equipment or devices; 6 of these had removal of these devices in conjunction with antibiotic therapy. The median duration of antibiotic therapy was 6 weeks (range 6–31). The median duration of aminoglycoside therapy was 28 days (range 6–43). Seven patients developed nephrotoxicity, 5 of whom received an aminoglycoside in combination with vancomycin. Male patients had a higher risk of developing nephrotoxicity compared with females (p = 0.04). The mean ± SD duration of EIAD before the development of nephrotoxicity was 34 ± 8 days. Clinical cure was achieved in 12 (75%) patients. Three patients achieved clinical cure without hardware removal.

CONCLUSIONS:

Most of the patients with gram-positive osteomyelitis were successfully managed with EIAD. However, nephrotoxicity developed in a high proportion of patients and was likely related to prolonged aminoglycoside use.
The First Boomer: Bill Clinton, George W., and Fictions of State
Authors: LOTT ERIC
Published: April 2004

ABSTRACT This essay discusses the way our images of the presidency dictate our relationship with governmental structures of all kinds—also known as the state. I consider how two recent presidents' generational status as baby boomers defines them in particular ways. For Clinton, his “blackness” generated his evasive aura of post-1960s hipness; for Bush, his status as “rightful heir,” center of a long-awaited “Restoration” of pre-1960s values, now legitimizes his call for a reawakened imperial patriotism.
Shadows
Authors: ABEL ELIZABETH
Published: April 2004

ABSTRACT This essay traces the relationship of Hollywood blackface to the figure of the shadow in the moving and still pictures of the 1930s. By reading Fred Astaire's Swing Time (1936) against Al Jolson's The Jazz Singer (1927), I argue that the shadow linked the breakthroughs in thirties cinematography with a distinctively Protestant variant of cinematic blackface.
Escape from Alienation: Challenges to the Nation-State
Authors: JACOBSON NORMAN
Published: April 2004

ABSTRACT The specter that haunts the thinking of the modern West is alienation, the bugaboo of intellectuals from left to right, and the nation-state is both a contributor to the uneasiness generated by alienation and the beneficiary of its consequences. Learning to live with alienation is the equivalent in the political sphere of the relinguishment of the security blanket of our infancy.
National Identity and Shifting Imperial Frontiers: Whiteness and the Exclusion of Colonial Labor After World War I
Authors: STOVALL TYLER
Published: April 2004

ABSTRACT This article addresses both the specific history and the broader implications of France's expulsion of colonial labor after World War I. The article also considers questions of race, immigration, and exoticist culture during the interwar years, showing that the French fascination with the Other reflected a determination to confirm a national identity as white. The use and expulsion of colonial labor in effect transferred a central colonial focus, racial identity, to the metropole.
American Naturalism and Asiatic Racial Form: Frank Norris's The Octopus and Moran of the “Lady Letty”
Authors: LYE COLLEEN
Published: April 2004

ABSTRACT American literary naturalism is well known for its formal engagement with determination and abstraction and its thematic preoccupation with Anglo-Saxon degeneration. Yet the central importance of the U.S.-Asian border to the literature's elaboration of the imperial contradictions of monopoly finance capitalism has been largely overlooked. Taking up the question of U.S. anti-Asian anticapitalism, a political movement with which American naturalism was historically coincident, this essay explores the powerful early twentieth-century consensus that permitted the conflation of trust-busting and coolie-fighting.
Anisotropic Properties of Conducting Polymers Prepared by Liquid Crystal Templating
Authors: Hulvat J. F. , Stupp S. I.
Published: April 2004

Anisotropic films of poly(3,4‐ethyldioxythiophene) (PEDOT) have been prepared by polymerization in an aqueous, self‐organized liquid crystalline template. The cylindrical, hydrophobic cores of the hexagonal template direct electropolymerization, producing films with anisotropic optical absorption and conductivity (see Figure).
Coiled‐Coil Peptide‐Based Assembly of Gold Nanoparticles
Authors: Stevens M. M. , Flynn N. T. , Wang C. , Tirrell D. A. , Langer R.
Published: April 2004

The coiled‐coil‐based assembly of gold nanoparticles (see Figure and cover) is demonstrated. Control over the assembly and disassembly of nanostructures is achieved under mild conditions (near‐neutral pH and ambient temperature). The flexibility in design afforded by varying the peptide sequence to produce coiled coils with different stabilities is also highlighted by the generation of more stable binary nanoparticle systems with controlled spacing and architecture.
Carbon Nanotubes with Graphitic Wings
Authors: Trasobares S. , Ewels C. P. , Birrell J. , Stephan O. , Wei B. Q. , Carlisle J. A. , Miller D. , Keblinski P. , Ajayan P. M.
Published: April 2004

Graphitic platelets (wings) on carbon nanotubes are produced using a new two‐step chemical vapor deposition method (see Figure and inside cover). Chemical attack during the process, aided by curvature‐induced strain, rips open the outer nanotube walls and produces an irregular and corrugated surface. The new morphology, which presents a highly modulated and active nanotube surface, could facilitate posterior functionalization or direct composite fabrication.
Efficient Organic Electrophosphorescent White‐Light‐Emitting Device with a Triple Doped Emissive Layer
Authors: D'Andrade B. W. , Holmes R. J. , Forrest S. R.
Published: April 2004

An organic electrophosphorescent white‐light‐emitting device (see Figure) containing green, red, and blue emitters doped into a 9 nm thick wide‐bandgap material is shown to attain a maximum forward viewing power efficiency of (26±3) lm W–1. The high power efficiency is attributed to the efficient confinement of excitons and charge within the emissive layer, a thin emissive layer, and highly efficient blue electrophosphorescent dopant.
Identification of 14 rare marker chromosomes and derivatives by spectral karyotyping in prenatal and postnatal diagnosis
Authors: Guanciali‐Franchi Paolo , Calabrese Giuseppe , Morizio Elisena , Fantasia Donatella , Colosimo Alessia , Rinaldi Maria M. , Cristini Luciano , Simonelli Andrea , Lonardo Fortunato , Turci Alessandra , Zatterale Adriana , Laganà Carmelo , Stuppia Liborio , Sabatino Giuseppe , Palka Giandomenico
Published: April 2004

Extra structurally abnormal chromosomes (ESACs) and cryptic rearrangements are often associated with mental retardation and phenotypic abnormalities. In some cases their characterisation, using standard cytogenetic techniques and fluorescence in situ hybridization (FISH), is difficult and time consuming, where a fast and accurate identification is essential, especially when such chromosomal aberrations are found in prenatal diagnosis. A recent molecular technique, spectral karyotyping (SKY), based on the spectral signature of 24 chromosome‐specific painting probes labelled with different combinations of five fluorochromes, allows the simultaneous visualisation of all human chromosomes in different colours. We used SKY analysis on 14 cases with rare ESACs or cryptic unbalanced rearrangements found at pre‐ or postnatal diagnosis. SKY analysis permitted the classification of chromosome rearrangements in all 14 cases analysed in combination with FISH analysis. © 2004 Wiley‐Liss, Inc.
Association between the brain‐derived neurotrophic factor 196G/A polymorphism and eating disorders
Authors: Koizumi Hiroki , Hashimoto Kenji , Itoh Kanako , Nakazato Michiko , Shimizu Eiji , Ohgake Shintaro , Koike Kaori , Okamura Naoe , Matsushita Sachio , Suzuki Kenji , Murayama Masanobu , Higuchi Susumu , Iyo Masaomi
Published: April 2004

Several lines of evidence suggest that genetic factors might contribute to the pathogenesis of eating disorders and that brain‐derived neurotrophic factor (BDNF) plays a role in the pathophysiology of eating disorders. To investigate the role of the BDNF gene in the susceptibility to eating disorders, we analyzed the BDNF 196G/A gene polymorphism in female patients with eating disorders and female normal controls. The difference in the genotype frequency between patients (n = 198) and normal controls (n = 222) was statistically significant (P = 0.029). Interestingly, a significant (P = 0.015) difference in the genotype frequency between normal controls and bulimia nervosa patients (n = 101) with binge‐purging type was detected. This study suggests that the BDNF 196G/A gene polymorphism might be associated with a susceptibility to eating disorders.© 2003 Wiley‐Liss, Inc.
Direct analysis of the genes encoding G proteins GαT2, Gαo, GαZ in ADHD
Authors: Turic D. , Langley K. , Kirov G. , Owen M.J. , Thapar A. , O'Donovan M.C.
Published: April 2004

We have followed up the extensive replicated evidence that the dopamine DRD4 receptor is involved in the aetiology of ADHD by undertaking direct analysis of genes encoding other proteins in this effector system. We prioritised the genes encoding G protein α subunits GαT2, Gαo, GαZ as these have been shown to transduce the effects of ligand binding at DRD4. We screened the exons of all three genes for sequence variation in 28 unrelated subjects with ADHD and identified 13 novel polymorphisms. All were tested for possible association with ADHD using a combination of pooled and individual genotyping. The results of our study do not suggest that polymorphisms in these genes contribute to susceptibility to ADHD. © 2004 Wiley‐Liss, Inc.
Rotationplasty about the knee:
Authors: Fuchs B. , Sim F.H.
Published: April 2004

Rotationplasty is an intercalary resection of a bone segment with subsequent reconstruction of the lower limb by rotating it through an arc of 180°. After rotation, the rotated ankle functions as a knee joint, thereby powering a custom‐made below‐knee prosthesis. Rotationplasty is a satisfactory treatment option in selected patients. A prerequisite for this type of surgery is an intact sciatic nerve. Rotationplasty is indicated for skeletally immature patients with a tumoral lesion about the knee (<8–10 years of age), for older patients with large lesions that are not candidates for limb salvage as an alternative to above‐knee amputation, and as a salvage procedure for chronically infected prosthetic implants. Preoperative planning includes the prediction of the exact remaining bone growth, because the ipsilateral distal tibial epiphysis will not completely substitute for the growth deficit resulting from the resected distal femoral and proximal tibial epiphyses. Therefore, minimal over length of the ankle of the operated leg is retained. Technical details of the surgery are described with particular emphasis on anatomical considerations. It provides a durable and biologic reconstruction and allows patients to become good functional below‐knee prosthesis users and allows participation in recreational activities and sports. Clin. Anat. 17:345–353, 2004. © 2004 Wiley‐Liss, Inc.
Anatomical basis for a successful upper limb sympathectomy in the thoracoscopic era
Authors: Ramsaroop L. , Singh B. , Moodley J. , Partab P. , Satyapal K.S.
Published: April 2004

In this clinico‐anatomical study, factors potentially responsible for unsuccessful upper limb sympathectomy (ULS) by the thoracoscopic route were evaluated. This study comprised two subsets: 1) in the clinical subset, 25 patients (n = 50 sides) underwent bilateral second thoracic ganglionectomy for palmar hyperhidrosis, and factors predisposing to unsuccessful ULS were identified; and 2) in the anatomical subset, the neural connections of the first and second intercostal spaces were bilaterally dissected in 22 adult cadavers (22 right, 21 left; n = 43 sides). Alternate neural pathways (ANP) were noted in 9 of 50 sides in the 25 clinical cases (18%). In three asthenic patients (5 sides), fascia overlying the longus colli muscle mimicked the sympathetic chain. The right superior intercostal vein (SIV) was located anterior to the second thoracic ganglion in 6 of 50 sides (12%) and predisposed to troublesome bleeding in 2 of 50 cases; the SIV was posterior to the ganglion in 19 of 50 sides (38%), posing no technical problem. On the left, the SIV was noted outside the field of dissection in all but one case. A successful outcome to sympathectomy was noted in all 25 patients. A spectrum of sympathetic contributions to the first thoracic ventral ramus for the first intercostal space was noted in 37 of 43 anatomical cases (86%). These were categorized according to the arrangements of the intrathoracic ramus between the second intercostal nerve and the first thoracic ventral ramus. The cervicothoracic ganglion (37/43 cases; 86%) and an independent inferior cervical ganglion (6/43 cases; 14%) were always located above the second rib. The second thoracic ganglion was consistently located in the second intercostal space. This study demonstrates that ANPs have little clinical significance when a second thoracic ganglionectomy is undertaken. Technical failures may be avoided if the surgeon is mindful of anatomical variations at surgery. Clin. Anat. 17:294–299, 2004. © 2004 Wiley‐Liss, Inc.