bluuebunny/crossref_metadata_2025 huggingface dataset:
α1 integrin activation: A link between β‐amyloid deposition and neuronal death in aging hippocampal neurons
Authors: Anderson Kelsi L. , Ferreira Adriana
Published: February 2004

A growing body of evidence obtained using in vitro model systems indicates that the deposition of fibrillar β‐amyloid (Aβ) results in neurite degeneration and cell death in central neurons. Little is known, however, about the molecular mechanisms underlying these neurotoxic effects. We have shown previously that fibrillar Aβ induced sustained activation of the mitogen‐activated protein kinase (MAPK) followed by hyperphosphorylation of tau proteins in aging hippocampal neurons. Furthermore, the blockage of MAPK activation using specific inhibitors prevented neurite degeneration in these cells. These results suggested that the MAPK signal transduction pathway could play a key role in Aβ‐induced neurite degeneration. We sought to identify upstream elements of the MAPK signaling cascade activated by Aβ deposition. We evaluated the participation of the integrins in this pathway by monitoring the activation of MAPK in the presence of specific integrin inhibitors. Our results indicate that pretreatment of mature hippocampal neurons with either echistatin or α1 integrin‐blocking antibodies prevented Aβ‐induced MAPK activation. In addition, the blockage of α1 activation prevented cell death induced by Aβ. Similar results were obtained when α1 and β1 integrin blocking antibodies were used combined. Taken collectively, these results identify α1 integrin and the α1 plus β1 integrin complexes as potential targets for therapeutic intervention in the Aβ signaling pathway in aging neurons. © 2004 Wiley‐Liss, Inc.
Quantification of hemorphins in Alzheimer's disease brains
Authors: Poljak Anne , McLean Catriona A. , Sachdev Perminder , Brodaty Henry , Smythe George A.
Published: February 2004

The hemorphins are a family of opioid receptor‐binding peptides originating from the β‐chain of hemoglobin and have been found at high levels within the central and peripheral nervous systems. In addition to opioid receptor binding, hemorphins have been shown to have a number of effects on the renin‐angiotensin system, including inhibition of angiotensin‐converting enzyme and angiotensin IV receptor binding. However, relatively few studies have examined the role of hemorphins in neurological diseases. Here we report the first study of hemorphins in Alzheimer's disease (AD) brains. Quantitative MALDI‐TOF mass spectrometry was employed to assess levels of LVV and VV hemorphin‐6 and ‐7 in 10 control and 10 AD brain tissue samples. LVV hemorphin‐6 and total hemorphin levels were elevated in AD temporal neocortex but not in hippocampus, occipital lobe, or frontal lobe. The elevation of hemorphins is probably indicative of a vascular abnormality resulting from cerebral amyloid angiopathy associated with both neurodegenerative disease and aging. © 2004 Wiley‐Liss, Inc.
Comparison of nerve terminal events in vivo effecting retrograde transport of vesicles containing neurotrophins or synaptic vesicle components
Authors: Weible M.W. , Ozsarac N. , Grimes M.L. , Hendry I.A.
Published: February 2004

Although vesicular retrograde transport of neurotrophins in vivo is well established, relatively little is known about the mechanisms that underlie vesicle endocytosis and formation before transport. We demonstrate that in vivo not all retrograde transport vesicles are alike, nor are they all formed using identical mechanisms. As characterized by density, there are at least two populations of vesicles present in the synaptic terminal that are retrogradely transported along the axon: those containing neurotrophins (NTs) and those resulting from synaptic vesicle recycling. Vesicles containing nerve growth factor (NGF), NT‐3, or NT‐4 had similar densities with peak values at about 1.05 g/ml. Synaptic‐derived vesicles, labeled with anti‐dopamine β‐hydroxylase (DBH), had densities with peak values at about 1.16 g/ml. We assayed the effects of pharmacologic agents in vivo on retrograde transport from the anterior eye chamber to the superior cervical ganglion. Inhibitors of phosphatidylinositol‐3‐OH (PI‐3) kinase and actin function blocked transport of both anti‐DBH and NGF, demonstrating an essential role for these molecules in retrograde transport of both vesicle types. Dynamin, a key element in synaptic vesicle recycling, was axonally transported in retrograde and anterograde directions, and compounds able to interfere with dynamin function had a differential effect on retrograde transport of NTs and anti‐DBH. Okadaic acid significantly decreased retrograde axonal transport of anti‐DBH and increased NGF retrograde transport. We conclude that there are both different and common proteins involved in endocytosis and targeting of retrograde transport of these two populations of vesicles. © 2004 Wiley‐Liss, Inc.
Fc receptors and the common γ‐chain in experimental autoimmune encephalomyelitis
Authors: Szalai Alexander J. , Barnum Scott R.
Published: February 2004

Fcγ receptors (FcγRs), composed of a ligand‐binding α‐chain (FcRα) sometimes associated with the homodimeric, cell‐signaling common γ‐chain (FcRγ), comprise an important family of effector molecules linking humoral and cell‐mediated adaptive immunity and regulating innate immunity. In peripheral autoimmune diseases, FcγRs contribute to inflammation and tissue damage through inappropriate activation of macrophages and neutrophils, release of cytokines and oxidants, and destruction of autoantibody‐opsonized cells. In the central nervous system (CNS), the role of FcγRs in autoimmune disease such as multiple sclerosis (MS) remains largely unexplored despite extensive documentation of CNS‐specific antibodies in cerebrospinal fluid and plaques. Several studies have now examined the role of FcγRs in experimental autoimmune encephalomyelitis (EAE), the animal model for MS, using mice genetically deficient in one or more FcγRs or in FcRγ. These studies indicate that none of the FcγR α‐chains are critical for EAE development and progression. In contrast, it is unequivocal that FcRγ contributes to EAE, and surprisingly it seems that this effect is independent of FcγRs. Recent studies now indicate that FcRγ expression in γδ T cells, most likely as a component of the TCR/CD3 signaling complex, is a critical requirement for EAE development. These studies support previous evidence implicating a pathogenic role for γδ T cells in EAE. © 2004 Wiley‐Liss, Inc.
Curcumin has potent anti‐amyloidogenic effects for Alzheimer's β‐amyloid fibrils in vitro
Authors: Ono Kenjiro , Hasegawa Kazuhiro , Naiki Hironobu , Yamada Masahito
Published: February 2004

Inhibition of the accumulation of amyloid β‐peptide (Aβ) and the formation of β‐amyloid fibrils (fAβ) from Aβ, as well as the destabilization of preformed fAβ in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine‐related polyphenols inhibit fAβ formation from Aβ(1–40) and Aβ(1–42) and destabilize preformed fAβ(1–40) and fAβ(1–42) dose‐dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and destabilization of fAβ(1–40) and fAβ(1–42) at pH 7.5 at 37°C in vitro. We next compared the anti‐amyloidogenic activities of Cur and RA with NDGA. Cur and RA dose‐dependently inhibited fAβ formation from Aβ(1–40) and Aβ(1–42), as well as their extension. In addition, they dose‐dependently destabilized preformed fAβs. The overall activities of Cur, RA, and NDGA were similar. The effective concentrations (EC50) of Cur, RA, and NDGA for the formation, extension, and destabilization of fAβs were in the order of 0.1–1 μM. Although the mechanism by which Cur and RA inhibit fAβ formation from Aβ and destabilize preformed fAβ in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD. © 2004 Wiley‐Liss, Inc.
Cell adhesion molecule L1 promotes neurite outgrowth of septal neurons
Authors: Frappé Isabelle , Wang Christine , Caines Geoffrey , Rideout‐Gros Shawna , Aubert Isabelle
Published: February 2004

To establish if the cell adhesion molecule L1 could promote neurite outgrowth of septal neurons, L1‐positive substrates were prepared by genetically modifying 3T3 fibroblasts with a retroviral vector encoding human L1 under the control of a negative tetracycline‐regulatory system. In several clones of L1‐transfected fibroblasts, L1 expression at the cell surface was prominent and efficiently regulated by doxycycline, a tetracycline analogue. In co‐culture of septal neurons and fibroblasts, a two‐dimensional fractionator probe provided systematic random sampling of the neurites to be measured. Septal neurons, isolated at embryonic Day 17, were found to express L1 in vitro and to extend significantly longer neurites when plated on L1‐expressing fibroblasts compared to control fibroblasts. The neurite outgrowth‐promoting effect of L1 was inhibited after a doxycycline treatment, which specifically suppressed L1 expression from the modified fibroblasts. The findings that septal neurons at embryonic Day 17 in vitro express L1 and respond to L1‐modulation suggest that this molecule is involved in development of the septohippocampal pathway. © 2004 Wiley‐Liss, Inc.
Oxidation of vitamin E and vitamin C and inhibition of brain mitochondrial oxidative phosphorylation by peroxynitrite
Authors: Vatassery Govind T. , Lai James C.K. , DeMaster Eugene G. , Smith W. Ed , Quach Hung T.
Published: February 2004

The effects of peroxynitrite (PN; product of the reaction between nitric oxide and superoxide) on mitochondrial respiration as well as oxidation of α‐tocopherol and ascorbic acid were studied. Mitochondria were isolated from brain hemispheres of 4‐month‐old male Fisher rats by standard centrifugation procedures utilizing Ficoll gradients. Treatment of brain mitochondria with PN caused a concentration‐dependent impairment of oxidative phosphorylation and depletion of the endogenous antioxidants α‐tocopherol and ascorbic acid. PN‐induced mitochondrial dysfunction was characterized by 1) decreases in state 3 respiration and oxidative phosphorylation, 2) loss of respiratory control [ratio of ADP‐stimulated (state 3) to basal (state 4) respiration], and 3) uncoupling of oxidative phosphorylation. PN did not function as a pure uncoupler, insofar as the increase in state 4 respiration was accompanied by a larger decrease in state 3 respiration. This contrasts with the uncoupling action of the protonophore carbonyl cyanide m‐chlorophenylhydrozone, which increases both state 3 and state 4 respiration. PN‐induced reduction in respiratory control and oxidative phosphorylation closely paralleled the oxidation of membrane tocopherol and were preceded by loss of ascorbate. α‐Tocopherol (the most potent biological lipid antioxidant) may have a unique role in protecting mitochondrial membranes from oxidative stress. The two antioxidant nutrients α‐tocopherol and ascorbate (which interact with each other and glutathione) may be intimately involved in protecting mitochondria in situations in which excessive release of superoxide and nitric oxide occurs under normal and/or pathological conditions. © 2004 Wiley‐Liss, Inc.
Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP‐1‐associated regulator of cyclin B, in Alzheimer's disease
Authors: Zhu Xiongwei , McShea Andrew , Harris Peggy L.R. , Raina Arun K. , Castellani Rudy J. , Funk Jens Oliver , Shah Sapan , Atwood Craig , Bowen Richard , Bowser Robert , Morelli Laura , Perry George , Smith Mark A.
Published: February 2004

Adult neurons are generally accepted to be in a quiescent, nonproliferative state. However, it is becoming increasingly apparent that, in Alzheimer's disease (AD), alterations in cell cycle machinery, suggesting an attempt to reenter cell cycle, relate temporally and topographically to degenerating neurons. These findings, together with the fact that neurons lack the necessary components for completion of mitosis, have led to the notion that an ill‐regulated attempt to reenter the cell cycle is associated with disease pathogenesis and, ultimately, neuronal degeneration. To understand better the role of such cell cycle abnormalities in AD, we undertook a study of CIP‐1‐associated regulator of cyclin B (CARB), a protein that associates with two key proteins, p21 and cyclin B, involved in cellular checkpoints in the cell cycle. Our results show that there are increases in CARB localized to intraneuronal neurofibrillary tangles and granulovacuolar degeneration in susceptible hippocampal and cortical neurons in AD. By marked contrast, CARB is found only at background levels in these neuronal populations in nondiseased age‐matched controls. Our data not only provide another line of evidence indicative of cell cycle abnormalities in neurons in AD but also lend further credence to the hypothesis that susceptible neurons may be arrested at the G2/M phase of the cell cycle before they die. Therefore, therapeutics targeted toward initiators of the cell cycle are likely to prove of great efficacy for the treatment of AD. © 2004 Wiley‐Liss, Inc.
Acute transplantation of olfactory ensheathing cells or Schwann cells promotes recovery after spinal cord injury in the rat
Authors: García‐Alías Guillermo , López‐Vales Rubén , Forés Joaquim , Navarro Xavier , Verdú Enrique
Published: February 2004

We compared the neurological and electrophysiological outcome, glial reactivity, and spared spinal cord connectivity promoted by acute transplantation of olfactory ensheathing cells (group OEC) or Schwann cells (group SC) after a mild injury to the rat spinal cord. Animals were subjected to a photochemical injury of 2.5 min irradiation at the T8 spinal cord segment. After lesion, a suspension containing 180,000 OECs or SCs was injected. A control group (group DM) received the vehicle alone. During 3 months postsurgery, behavioral skills were assessed with open field‐BBB scale, inclined plane, and thermal algesimetry tests. Motor (MEPs) and somatosensory evoked potentials (SSEPs) were performed to evaluate the integrity of spinal cord pathways, whereas lumbar spinal reflexes were evaluated by the H reflex responses. Glial fibrillary acidic protein and proteoglycan expressions were quantified immunohistochemically at the injured spinal segments, and the preservation of corticospinal and raphespinal tracts caudal to the lesion was evaluated. Both OEC‐ and SC‐transplanted groups showed significantly better results in all the behavioral tests than the DM group. Furthermore, the OEC group had higher MEP amplitudes and lower H responses than the other two groups. At the injury site, the area of spared parenchyma was greater in transplanted than in control injured rats. OEC‐transplanted animals had reduced astrocytic reactivity and proteoglycan expression in comparison with SC‐transplanted and DM rats. Taken together, these results indicate that transplantation of both OEC and SC has potential for restoration of injured spinal cords. OEC grafts showed superior ability to reduce glial reactivity and to improve functional recovery. © 2004 Wiley‐Liss, Inc.
Neural precursor cells derived from human embryonic brain retain regional specificity
Authors: Horiguchi Satoshi , Takahashi Jun , Kishi Yo , Morizane Asuka , Okamoto Yo , Koyanagi Masaomi , Tsuji Masayuki , Tashiro Kei , Honjo Tasuku , Fujii Shingo , Hashimoto Nobuo
Published: February 2004

Recent studies have revealed that neural precursor cells can be expanded not only from the subventricular zone and hippocampus but also from other regions of the human embryonic brain. To determine the regional differences of these precursor cells, we divided the brain of a 9‐week‐old human embryo into four parts, i.e., telencephalon, diencephalon, mesencephalon, and rhombencephalon. All cultures of the tissues yielded neurospheres, and these spheres gave rise to neurons, astrocytes, and oligodendrocytes. An analysis of clonal populations revealed that these precursor cells were multipotent, and two region‐specific differences in neural precursor cells were revealed: 1) The precursor cells from the rostral part of the brain tended to proliferate faster than those from the caudal part, and 2) the precursor cells from the diencephalon and mesencephalon gave rise to more tyrosine hydoxylase (TH)‐positive neurons than those from the telencephalon and rhombencephalon. When 50‐day‐cultured spheres were caused to differentiate, the percentage of TH‐positive cells per total cell population was 1.2% for diencephalic and mesencephalic precursors, whereas it was 0.4% for telencephalic and rhombencephalic ones. Furthermore, the TH‐positive cells from diencephalic and mesencephalic precursors were large, multipolar, and γ‐aminobutyric acid (GABA)‐negative, which suggested that these cells were midbrain dopaminergic neurons. In contrast, TH‐positive cells from telencephalic and rhombencephalic precursors were small, bipolar, and GABA‐positive. These results suggest that human neural precursor cells might have the potential to differentiate into a variety of cells but retain regional specificity. © 2004 Wiley‐Liss, Inc.
Nerve growth factor, brain‐derived neurotrophic factor, and neurotrophin‐3 are sorted to dense‐core vesicles and released via the regulated pathway in primary rat cortical neurons
Authors: Wu Y.J. , Krüttgen A. , Möller J.C. , Shine D. , Chan J.R. , Shooter E.M. , Cosgaya J.M.
Published: February 2004

Neurotrophins (NTs) play an important role in the modulation of synaptic transmission and in morphological changes in synaptic structures. Although there is agreement that brain‐derived neurotrophic factor (BDNF) is sorted to large dense‐core vesicles (LDCVs) and released via the regulated secretory pathway, there has been some dispute regarding the mode of secretion of nerve growth factor (NGF) and neurotrophin‐3 (NT‐3), two structurally related members of the NT family. In this study, we examined the subcellular localization and release characteristics of NGF, BDNF, and NT‐3 in adenovirus‐infected primary cortical neurons. We found that all members of the NT family colocalized with markers for the endoplasmic reticulum and Golgi within cell bodies and in a punctate manner with a marker for LDCVs within processes. Moreover, their release was triggered by depolarization, indicating that NGF, BDNF, and NT‐3 are released via the regulated secretory pathway. When neurons were coinfected with two separate adenoviruses coding for NGF or BDNF, both NTs showed almost complete vesicular colocalization within single cells, suggesting that different NTs might be packaged into shared vesicles. We also examined whether the two splice variants of NGF, the short and long precursors, differ in their release characteristics. We found that neurons infected with viruses coding for either splice variant released NGF in a regulated way. Overall, our study supports the notion that all members of the NT family undergo activity‐dependent regulated release from neurons, enabling them to act as “synaptotrophins” on electrically active neurons. © 2004 Wiley‐Liss, Inc.
Cytoplasmic domain of NCAM 180 reduces NCAM‐mediated neurite outgrowth
Authors: Büttner Bettina , Reutter Werner , Horstkorte Rüdiger
Published: February 2004

The neural cell adhesion molecule (NCAM) is one of the best‐characterized cell adhesion molecules of the immunoglobulin superfamily. In the nervous system, NCAM is involved in cell migration, axon fasciculation and in neurite outgrowth. Neurite outgrowth is mediated by homophilic NCAM‐NCAM interactions. Alternative splicing generates three major isoforms of NCAM differing in their intracellular portion. Two of them, NCAM 180 and NCAM 140, are transmembrane proteins with large intracellular domains. The present study is concerned with novel details of the intracellular domains of NCAM 140 and NCAM 180. We expressed these NCAM isoforms consisting only of the transmembrane and intracellular domains (without extracellular domains) in PC12 cells and elaborated their function in neurite outgrowth assays. Our data demonstrate that membrane‐associated NCAM 180 interferes with neurite outgrowth, whereas membrane‐associated NCAM 140 promotes neurite outgrowth. © 2004 Wiley‐Liss, Inc.
Neuronal MEK is important for normal fear conditioning in mice
Authors: Shalin Sara C. , Zirrgiebel Ute , Honsa Katya J. , Julien Jean‐Pierre , Miller Freda D. , Kaplan David R. , Sweatt J. David
Published: February 2004

The extracellular signal‐regulated kinase (ERK) cascade has received much attention for its possible role in neuronal synaptic plasticity. Although ERK activation has been linked to learning behaviors and activity‐dependent neuronal function, much of the acquired data has relied upon pharmacological agents that suppress ERK function in both neurons and nonneuronal cells. To determine the function of neuronal ERK activity in learning, a new line of transgenic mice was generated wherein dominant‐negative MEK1, the upstream obligate activator of ERK1/2, was expressed by using a neuronal‐specific and pan‐neuronal Tα1 α‐tubulin promoter element. Mice expressing this construct exhibited decreased ERK1/2 activity in the hippocampus and thus were tested for learning impairments. In a battery of control tests, including open field, rotarod, and shock threshold, the transgenic mice displayed no deficits and performed as well as their wild‐type littermate counterparts. However, the mice displayed a significant impairment in contextual fear conditioning compared with the wild‐type littermates. These findings indicate that the MEK1/ERK1/2 cascade within neurons plays an important role in the processes of learning and memory. © 2004 Wiley‐Liss, Inc.
Glucose transporter GLUT8 translocation in neurons is not insulin responsive
Authors: Shin Bo‐Chul , McKnight Robert A. , Devaskar Sherin U.
Published: February 2004

We examined the subcellular distribution of a novel glucose transporter isoform (GLUT8) in murine N2A neuroblastoma cells. Exogenous expression of GLUT8‐green fluorescent protein (GFP) DNA constructs mimicked the endogenous GLUT8 localization to intracellular vesicles and minimally to the Giantin‐positive Golgi. This distribution was unlike the distributions of endogenous GLUT1 and GLUT3 (predominant neuronal isoform), which were limited predominantly to the plasma membrane and minimal in the cytoplasm. Although GLUT4‐GFP (insulin responsive isoform) was expressed transiently, no endogenous GLUT4 was detected in N2A cells. By employing stable transfectants that expressed GLUT8‐GFP, the effect of insulin and insulin‐like growth factor‐I, potassium chloride (depolarized state), and 3% oxygen on translocation of GLUT8 to the plasma membrane of N2A cells was examined immunohistochemically and by subfractionation, followed by Western blot analysis. None of these agents translocated GLUT8 to the plasma membrane. However, when the internalization dileucine motif (L12,13) of GLUT8 was mutated to a dialanine motif (A12,13), GLUT8 colocalized with GLUT3 in the plasma membrane. We conclude that GLUT8 translocation to the N2A cellular plasma membrane is not observed secondary to the various stimuli investigated. Mutation of the N‐terminal dileucine motif led to constitutive GLUT8 localization in the plasma membrane. The endogenous stimulus required for translocating neuronal GLUT8 is unknown. This stimulus, which is necessary for uncoupling the “cytoplasmic vesicular anchor” of GLUT8, would be crucial for its glucose‐transporting function. © 2004 Wiley‐Liss, Inc.
Ciliary neurotrophic factor overexpression in neural progenitor cells (ST14A) increases proliferation, metabolic activity, and resistance to stress during differentiation
Authors: Weinelt Sabine , Peters Sabine , Bauer Peter , Mix Eilhard , Haas Stefan J.P. , Dittmann Aline , Wree Andreas , Cattaneo Elena , Knoblich Rupert , Strauss Ulf , Rolfs Arndt
Published: February 2004

The original article to which this Erratum refers was published in Journal of Neuroscience Research (2003) 71(2) 228‐236
The business practices of small Chinese restaurants in the UK: an exploratory investigation
Authors: Chaudhry Shiv , Crick Dave
Published: February 2004

Owner‐managers of Chinese restaurants in the UK have a need to continually monitor their business practices to obtain an advantageous position in a competitive business environment.

Specific attention to elements of the ‘marketing mix’ — product, place, price and promotion — is likely to positively benefit many owner‐managed businesses.

Hiring and training of appropriate staff members is important in order to offer enhanced customer service.

This paper considers the importance of cultural factors within ethnic minority‐owned firms' business practices and provides a contribution to the growing body of knowledge at the marketing–entrepreneurship interface. Specifically, it reports on an empirical investigation into the business practices of a sample of Chinese‐owned restaurants operating in the UK. The findings from ten in‐depth personal interviews provide an insight into the practices of these businesses. The results indicate that particular cultural issues balanced against resource constraints had a major impact on owner‐managers' operations. Copyright © 2004 John Wiley & Sons, Ltd.
South Korean companies in transition: an evolving strategic management style
Authors: Lee Yang‐Im
Published: February 2004

South Korea has a unique socio‐cultural identity that results in the development of mutually oriented business relationships.

South Korean managers are loyal and respectful but are gradually learning to develop a risk‐oriented approach to decision‐making.

Although employees of South Korean companies are known for their ability to work in groups, they are becoming independent thinkers and more individualistic.

In the future, South Korean managers are likely to develop a more competitive nature to business as company growth and survival become priorities.

Copyright © 2004 John Wiley & Sons, Ltd.
The impact of the Internet on marketing priorities in the financial services industry
Authors: Harris Lisa , Coles Anne‐Marie
Published: February 2004

This paper examines the impact of the Internet upon marketing dynamics within UK banks. It draws upon ongoing empirical research in the retail sector of the financial services industry to report some preliminary findings as to the nature of change that is taking place.

A number of marketing strategies are emerging that can be categorized along a continuum between ‘evolutionary’ and ‘revolutionary’ change. Hence there are likely to be implications for the way in which banks are organized and managed.

The preliminary conclusions however, indicate that established norms seem to be enduring and online banking innovations are not in themselves transforming business priorities in the industry in the way that early predictions might have had us believe.

Copyright © 2004 John Wiley & Sons, Ltd.
Commercial activity in new university business schools: trends and predictions for the future
Authors: Prince Christopher , Beaver Graham
Published: February 2004

Commercial activity, or third leg activity as the Higher Education Funding Council for England (HEFCE) defines it, and the income it generates, is of increasing importance to all higher education institutions (DES, 2003; CEML, 2002).

For new or modern university business schools in particular, the falling unit of resource attaching to HEFCE student teaching income and the virtual disappearance of research revenues as a result of the poor results in the 2001 Research Assessment Exercise (RAE), has combined to produce a scenario in which commercial activity is likely to be an increasing priority as business schools attempt to remain effective and solvent.

Copyright © 2004 John Wiley & Sons, Ltd.
Total removal of the posterior mediastinal gastric conduit due to gastric cancer after esophagectomy
Authors: Akita Hirofumi , Doki Yuichiro , Ishikawa Osamu , Takachi Ko , Miyashiro Isao , Sasaki Yo , Ohigashi Hiroaki , Murata Kohei , Noura Shingo , Yamada Terumasa , Eguchi Hidetoshi , Imaoka Shingi
Published: February 2004

Background

Total removal of the gastric conduit (TRGC) due to gastric cancer after esophagectomy often results in high operative morbidity and mortality rates, especially when done in the posterior mediastinum. This is one of the reasons for the retro‐sternal or subcutaneous route being preferred for gastric conduit replacement in esophageal cancer operation.

Patients

Five out of 680 post‐operative esophageal cancer patients underwent TRGC via thoracotomy and laparotomy due to posterior mediastinal gastric conduit cancers.

Results

In these patients, advanced gastric cancers were found at an average of 84 months (ranging 57–136 months) after esophageal cancer surgery and preoperative risk factors for TRGC were found in age, nutrition, and pulmonary function. The operative time for TRGC was long (average 670 min) but not associated with operative complications, while blood loss varied among patients, with one with the most operative blood loss dying after surgery due to pyothorax and renal failure. This case, and another early case subjected to TRGC first with thoracotomy then followed by laparotomy, showed more operative blood loss (10,895 and 3,260 ml) than the later three patients (2,370, 1,900, and 1,780 ml), who underwent laparotomy before thoracotomy with ligation of the blood supply of the gastric conduit and lysis of adhesion around gastric conduit in the lower mediastinum from the abdomen.

Conclusion

TRGC in the posterior mediastinum would be safer if operative manipulation were started from laparotomy in order to reduce operative blood loss. J. Surg. Oncol. 2004;85:204–208. © 2004 Wiley‐Liss, Inc.
Application of minimally invasive treatment for early gastric cancer
Authors: Hyung Woo Jin , Cheong Jae Ho , Kim Junuk , Chen Jian , Choi Seung Ho , Noh Sung Hoon
Published: February 2004

Background and Objectives

Although various types of minimally invasive treatment have emerged as the best front‐line therapies for early gastric cancer (EGC), there have been no established indications that these attempts are applicable. The purpose of this study was to propose indications for the application of minimally invasive therapy for EGC.

Methods

A total of 566 patients with EGC who had undergone gastrectomy with D2 or more extended lymphadenectomy, from July 1993 to December 1997 were retrospectively analyzed. The risk factors that determine lymph node metastasis were investigated by univariate and multivariate analysis.

Results

The rate of lymph node metastasis was 11.8% for all EGC, 3.4% for mucosal cancer, and 21.0% for submucosal cancer. Lymph node metastasis was associated with submucosal invasion, larger tumor size, undifferentiated histology, and the presence of lymphatic or blood vessel invasion (LBVI) by univariate and multivariate analyses. When LBVI was absent, there was no lymph node metastasis if the tumor was smaller than 2.5 cm with differentiated histology, and smaller than 1.5 cm with undifferentiated histology, regardless of depth of invasion. Extra‐perigastric lymph node metastases were noted in patients with submucosal tumors that have LBVI while none of mucosal cancer showed extra‐perigastric lymph node metastases.

Conclusions

Minimally invasive treatment can be possibly applied for patients with EGC using these four independent risk factors for lymph node metastasis in EGC. For mucosal cancers, EMR is indicated for EGCs without lymph node involvement based on tumor size and histology. When we found LBVI by pathologic examination after EMR, gastrectomy with D1 lymph node dissection is mandatory. For submucosal cancers, patients with small tumors could be treated with laparoscopic wedge resection without lymph node dissection. However, patients with larger sized tumors or tumors with LBVI should be treated with extended (D2) lymph node dissection. J. Surg. Oncol. 2004;85:181–185. © 2004 Wiley‐Liss, Inc.
Solid and papillary epithelial neoplasm of the pancreas
Authors: Madan Atul K. , Weldon Christopher B. , Long William P. , Johnson David , Raafat Aml
Published: February 2004

Solid and papillary epithelial (SPEN) is an uncommon pancreatic tumor often seen in young females. Although most of these neoplasms have a benign course, SPEN do have malignant potential. Treatment is surgical which is usually feasible either via enucleation or more radical procedures. Below we discuss diagnosis, treatment, and prognosis in detail. J. Surg. Oncol. 2004;85:193–198. © 2004 Wiley‐Liss, Inc.
The effectiveness of complete decongestive physiotherapy for the treatment of lymphedema following groin dissection for melanoma
Authors: Hinrichs Christian S. , Gibbs John F. , Driscoll Deborah , Kepner James L. , Wilkinson Neal W. , Edge Stephen B. , Fassl Kathleen A. , Muir Robin , Kraybill William G.
Published: February 2004

Objective

Groin dissection is performed for the treatment of melanoma and other malignancies. Lymphedema rates as high as 47% have been reported. In 1996, we began using complete decongestive physiotherapy (CDP) in selected patients with lymphedema following groin dissection. Here, we review our results in a small cohort of patients.

Methods

A retrospective review of the medical records of 14 patients, treated with CDP for lymphedema secondary to groin dissection for melanoma was conducted. All patients were treated with CDP at Roswell Park Cancer Institute (RPCI), between 1996 and 2002. Of the 14 patients, 12 underwent groin dissection at RPCI. Response to therapy was measured by limb volume determinations. Patient gender, age, body mass index (BMI), type of operation, type of adjuvant therapy, time to treatment, patient compliance, lymphedema stage, and initial edema were analyzed for association with response to treatment. Incidence was estimated by a review of the operative logs.

Results

Fourteen patients were treated with CDP for lymphedema secondary to groin dissection for melanoma, with a median decrease in lymphedema of 60% (range: 35–145%; P = 0.0003). Increased BMI was associated with a decreased response to treatment (P = 0.02). Response to CDP was not effected by time to treatment, patient compliance, lymphedema stage, and initial edema. During this time, 39 groin dissections were done at RPCI. The incidence of lymphedema treated with CDP at RPCI was 31% (12/39; standard error 7.4%).

Conclusions

With a decrease in lymphedema of 60%, CDP may provide relief for patients with lymphedema following groin dissection. Elevated BMI was associated with a decreased response to CDP. J. Surg. Oncol. 2004;85:187–192. © 2004 Wiley‐Liss, Inc.
Histopathologic examination of axillary sentinel lymph nodes in breast carcinoma patients
Authors: Viale Giuseppe , Sonzogni Angelica , Pruneri Giancarlo , Maffini Fausto , Masullo Michele , Dell'Orto Patrizia , Mazzarol Giovanni
Published: February 2004

The axillary sentinel lymph node biopsy (SLNB) has gained increasing popularity as a novel surgical approach for staging patients with breast carcinoma and for guiding the choice of adjuvant therapy with minimal morbidity. Patients with negative SLNB represent a subset of breast carcinoma patients with definitely better prognosis, because their pN0 status is based on a very thorough examination of the sentinel lymph nodes (SLNs), with a very low risk of missing even small micrometastatic deposits, as compared with routine examination of the 20 or 30 lymph nodes obtained by the traditional axillary clearing. The histopathologic examination of the SLNs may be performed after fixation and embedding in paraffin, or intraoperatively on frozen sections. Whatever is the preferred tracing technique and surgical procedure, the histopathologic examination of each SLN must be particularly accurate, to avoid a false‐negative diagnosis. Unfortunately, because of the lack of standardised guidelines or protocols for SLN examination, different institutions still adopt their own working protocols, which differ substantially in the number of sections cut and examined, in the cutting intervals (ranging from 50 to more than 250 μm), and in the more or less extensive use of immunohistochemical assays for the detection of micrometastatic disease. Herein, a very stringent protocol for the examination of the axillary SLN is reported, which is applied either to frozen SLN for the intraoperative diagnosis, and to fixed and embedded SLN as well. J. Surg. Oncol. 2004;85:123–128. © 2004 Wiley‐Liss, Inc.
Radioguided sentinel lymph node biopsy in patients with malignant cutaneous melanoma: The nuclear medicine contribution
Authors: Mariani Giuliano , Erba Paola , Manca Gianpiero , Villa Giuseppe , Gipponi Marco , Boni Giuseppe , Buffoni Ferdinando , Suriano Sergio , Castagnola Franca , Bartolomei Mirco , Strauss H. William
Published: February 2004

As for other solid tumors, malignant cutaneous melanoma drains in a logical way through the lymphatic system, from the first to subsequent levels. Therefore, the first lymph node encountered (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Sentinel lymph node biopsy distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, and those with metastatic involvement who might benefit from additional therapy. This procedure represents a significant advantage as a minimally invasive procedure, considering that only an average 20% of melanoma patients with Breslow thickness between 1.5 and 4 mm harbour metastasis in their sentinel node(s) and are therefore candidates to elective lymph node dissection procedures. The cells that originate cutaneous melanomas are located between dermis and epidermis, a zone that drains to the inner lymphatic network in the reticular dermis, in turn to larger collecting lymphatics in subcutis. Therefore, the optimal modality of interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is through intradermal/subdermal injection. 99mTc‐labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas located in the midline area of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the node(s). The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is about 98% in institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. The procedure is becoming the standard of care for patients with cutaneous melanoma because of its high prognostic value that has led to include the procedure in the most recent version of the TNM staging system. J. Surg. Oncol. 2004;85:141–151. © 2004 Wiley‐Liss, Inc.
New fields of application of the sentinel lymph node biopsy in the pathologic staging of solid neoplasms: Review of literature and surgical perspectives
Authors: Gipponi Marco , Solari Nicola , Di Somma Franco C. , Bertoglio Sergio , Cafiero Ferdinando
Published: February 2004

Sentinel lymph node (sN) biopsy has gained special attention among surgical and medical oncologists as it represents an accepted technique for detecting occult nodal disease in regional lymph nodes of patients with melanoma and breast cancer. The histopathologic examination of the sN may well predict regional lymph node status in order to define the most suitable loco‐regional and systemic treatment. Recently, this technique has also been applied to other solid tumor types such as gynecologic and urologic malignancies, squamous head and neck cancer, thyroid cancer, non‐small‐cell lung cancer, Merkel cell carcinoma, and gastric cancer. The aim of this literature review is to define the rationale of sN biopsy in these tumor sites, the most effective procedure for sN detection, and the accuracy of the sN in predicting regional nodal status, as well as the surgical perspectives of sN biopsy application. J. Surg. Oncol. 2004;85:171–179. © 2004 Wiley‐Liss, Inc.
A computational study of the kinetics and mechanism for the reaction of HCO with HNO
Authors: Xu Z. F. , Lin M. C.
Published: February 2004

The mechanism for the reaction of HCO with HNO has been studied at the G2M level of theory, based on the geometric parameters optimized by the BH&HLYP/6‐311G(d, p) method. There are three direct hydrogen abstraction channels producing (1) H2CO + NO, (2) H2NO + CO, and (3) HNOH + CO with barriers of 3.7, 3.9, and 10.4 kcal/mol, respectively. Another important reaction channel, (4), involves an association process forming HN(O)CHO (LM1) with a very small barrier and the subsequent isomerization and decomposition of LM1 producing HNOH + CO as major products. The rate constants of the dominant reaction channels (1), (2), and (4) in the temperature range 200–3000 K have been predicted by the microcanonical RRKM and transition state theory calculations with Eckart tunneling corrections. The theoretical result shows that in the high temperature range ( T > 1500 K), k1 (H2CO + NO) and k2(H2NO + CO) are preponderant, while in the low temperature range, both k4(LM1) and k4(HNOH + CO) appear to be dominant at high and low pressures, respectively. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 205–215, 2004
Flashlamp pulsed dye laser (PDL) suppression of keloid proliferation through down‐regulation of TGF‐β1 expression and extracellular matrix expression
Authors: Kuo Yur‐Ren , Jeng Seng‐Feng , Wang Feng‐Sheng , Chen Tien‐Hsing , Huang Hui‐Chen , Chang Pei‐Rong , Yang Kuender D.
Published: February 2004

Background and Objectives

Keloids have been treated with flashlamp pulsed dye lasers (PDLs) with good results. We investigated whether PDL treatments induced keloid regression by decreasing growth factor‐β1 (TGF‐β1) induction, thereby reducing fibroblast proliferation and collagen deposition.

Study Design/Materials and Methods

Clinical evaluation and photography documented keloid height/texture, erythema, and pliability before and after PDL treatments scheduled at 2‐month intervals in 30 patients. Fluence per pulse was 10–18 J/cm2 (mean 14.0 J/cm2). Immunohistochemical (IHC) staining of TGF‐β1, proliferating cell nuclear antigen (PCNA), and collagen (types I and III) in extra‐cellular matrix was performed on 10 intra‐lesional or punch biopsies obtained before and 7 days after PDL treatments.

Results

Twelve months after final PDL treatments, keloid regression ( ≥ 50%) had occurred in 26/30 patients in whom erythema and surface irregularities had been reduced and pliability had been increased. In 4/30 patients, no changes in keloids had occurred after 12 months. Multiple treatments ( > 6) yielded better results than fewer treatments: 79% versus 50%, respectively. Marked keloid regression ( ≥ 90%) occurred in two patients who had received more than 10 treatments. IHC staining indicated that expression of TGF‐β1, PCNA and collagen type III, but not type I, was significantly reduced in keloid fibroblasts after PDL irradiation.

Conclusions

Keloids regressed following PDL‐induced reduction in TGF‐β1 expression, fibroblast proliferation, and collagen type III deposition. More than six PDL treatments at 2‐month intervals provided the best results. Lasers Surg. Med. 34:104–108, 2004. © 2004 Wiley‐Liss, Inc.
Laser treatment for neovascular formation
Authors: Raskin Boris , Fany Reis R.
Published: February 2004

Background and Objectives

Neovascular formation or matting [Davis and Duffy, J Dermatol Surg Oncol 1990; 16:327; Folkman and Klagsbrun, Science 1987;235:442; Weiss et al., Lasers Surg Med 1996;8:40–41] is a complex problems for doctors to treat. It was done by two different kinds of lasers, 532 nm [Silver and Livshots, Cosmetic Dermatol 1996;9:61; Adrian, Dermatol Surg 1998; 24:19] and 1,064 nm [Weiss and Weiss, Dermatol Surg 1999; 12:399–402] Nd:Yag laser. This study was carried out to discover which had better results on the treatment of this pathology.

Study Design/Materials and Methods

Thirty‐six patients underwent a monthly treatment, two sessions for neovascular formation by the 532 nm diode laser and the 1,064 nm [Weiss and Weiss, Dermatol Surg 1999;12:399–402] Nd:Yag laser. A comparative study was done by digital photography pre and post laser, 1 month after the second treatment by the two methods of evaluation, clinical percent clearance and by mathematically counting the number of vessels.

Results

There was a significant reduction of the number of capillaries in the affected areas treated by both lasers, mainly in the 1,064 Nd:Yag group.

Conclusions

The association of 3 and 10 mm spot size of the 1,064 nm laser group had better results compared with the 532 nm laser for matting treatment. Lasers Surg. Med. 34:189–192, 2004. © 2004 Wiley‐Liss, Inc.
Characterization of port wine stain skin erythema and melanin content using cross‐polarized diffuse reflectance imaging
Authors: Jung Byungjo , Choi Bernard , Durkin Anthony J. , Kelly Kristen M. , Nelson J. Stuart
Published: February 2004

Background and Objectives

Objective methods to assess quantitatively port wine stain (PWS) blanching in response to laser therapy are needed to improve laser therapeutic outcome. Previous studies have attempted to assess objectively PWS color based on point measurement devices. To date, these approaches have typically been limited by a number of factors such as small test area and need for contact. To address these issues, a cross‐polarized diffuse reflectance imaging system and color image analysis method has been developed to evaluate quantitatively erythema and melanin content in PWS skin.

Study Design/Materials and Methods

A cross‐polarized diffuse reflectance system has been constructed to acquire high resolution digital images while minimizing artifacts such as glare, shadowing, and nonuniform illumination effects that can compromise image fidelity. Furthermore, an image analysis algorithm has also been developed to analyze normal and PWS skin in terms of CIEL*a*b* color space parameters. Using the algorithm, images of color space intensity, L*, and saturation, a*, indices have been calculated to extract quantitative metrics of melanin and erythema, respectively.

Results

Compared to the cross‐polarized diffuse reflectance image, the a* index image enhanced the contrast in regions of high and low erythema and seems to have quasi correlation with the L* index image. In the presented PWS patient example, the relative a* index difference (Δa*) image showed less erythema in PWS skin after laser treatment when compared to pre‐treatment values.

Conclusions

Our cross‐polarized imaging system and color image analysis method is a simple, noncontact technique that can indirectly provide quantitative measurement of erythema and melanin content in PWS skin. Lasers Surg. Med. 34:174–181, 2004. © 2004 Wiley‐Liss, Inc.