bluuebunny/crossref_metadata_2025 huggingface dataset:
CFD studio: An educational software package for CFD analysis and design
Authors: Pieritz Romeu André , Mendes Rafael , da Silva Rodrigo F. A. F. , Maliska Clovis R.
Published: April 2004

This paper presents the general characteristics of the educational user‐friendly “CFD Studio” package designed for teaching fluid mechanics and heat transfer process, including conduction, coupled conduction/convection, natural and forced convection, external and internal flows. Therefore, general aspects of the three main modules—pre‐processor, solver, and post‐processor—are discussed aiming to show the generality of the tool. These modules are integrated in the application by a so‐called “numerical problem project” to guide the student through the steps to obtain the solution. © 2004 Wiley Periodicals, Inc. Comput Appl Eng Educ 12: 20–30, 2004; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10055
Synthesis of Functionalized 1,3‐Thiazine Libraries Combining Solid‐Phase Synthesis and Post‐Cleavage Modification Methods
Authors: Strohmeier Gernot A. , Haas Willibald , Kappe C. Oliver
Published: April 2004

The solid‐phase synthesis of diverse sets of 1,3‐thiazine‐5‐carboxylates on Wang resin is described. Acetoacetylation, followed by Knoevenagel condensation and an acid‐promoted ring‐closure reaction with thioureas furnished polymer‐bound 1,3‐thiazines. As an alternative to transesterification, a de‐novo synthesis of β‐keto esters, starting from polymer‐bound malonic acid through reaction with acyl imidazoles, was applied to increase the diversity. To reduce contamination, an on‐bead purification of resin‐bound 1,3‐thiazines that makes use of differences in the reactivity of ester bonds toward alkoxides is reported. A final four‐step post‐cleavage modification of thiazine‐5‐carboxylates, derived by TFA cleavage from the Wang linker, leads to esters or amides. Twenty 1,3‐thiazines were obtained in yields of up to 61 % over either 9 or 13 steps.
Reorganization of Enynes Catalyzed by Platinum Salts
Authors: Añorbe Loreto , Domínguez Gema , Pérez‐Castells Javier
Published: April 2004

Activation of alkynes with platinum salts allows their reaction with alkenes, giving rise to a myriad of interesting processes like cyclizations, formation of cyclopropanes, or metathesis. Weak nucleophiles can also participate in the processes leading to alkoxycyclizations. There are intriguing mechanistic aspects of these processes in which subtle variations of the reaction conditions and/or substrate structures can lead to completely different products.
Therapy of meningeal melanocytomas
Authors: Rades Dirk , Schild Steven E. , Tatagiba Marcos , Molina Hugo A. , Alberti Winfried
Published: April 2004

BACKGROUND

Meningeal melanocytomas are rare, benign central nervous system lesions with a high probability of recurrence. To the authors' knowledge, approximately 100 cases have been reported since 1972, when the entity first was described. In the current study, four therapies were compared with regard to local control and survival to identify which is best.

METHODS

All reported cases were reviewed with regard to extent of resection, radiotherapy, local control, and survival. If published data were incomplete, the authors were contacted for additional data. Patients were categorized by therapy: complete resection (CTR), complete resection followed by radiotherapy (CTR‐RT), incomplete resection (ITR), and incomplete resection followed by radiotherapy (ITR‐RT). Local control and survival were calculated using the Kaplan–Meier method. A multivariate analysis was performed including age, gender, tumor location, confirmation of extent of resection, and treatment schedule.

RESULTS

A total of 89 patients were included: 46 with CTR, 3 with CTR‐RT, 23 with ITR, and 17 with ITR‐RT. The 5‐year local control rate was 80% after CTR, 100% after CTR‐RT, and 72% after ITR‐RT versus 18% after ITR (P < 0.001). The 5‐year survival rate was 100% after CTR, CTR‐RT, and ITR‐RT, respectively, versus 46% after ITR (P < 0.001). Multivariate analysis demonstrated that therapy was the only variable that affected local control and survival significantly. In 14 patients treated with ITR‐RT, RT was restricted to the tumor region. The radiation dose was 30–40 grays (Gy) in 6 patients, 45–55 Gy in 7 patients, and unknown in 1 patient. The 5‐year local control rate was 86% after a dose of 45–55 Gy versus 27% after a dose of 30–40 Gy (P = 0.1).

CONCLUSIONS

CTR was found to be significantly superior to ITR with regard to both local control and survival. Outcome was significantly improved by RT after ITR. Doses of 45–55 Gy appeared to be more beneficial than doses of ≤ 40 Gy. Cancer 2004. © 2004 American Cancer Society.
Increase in motoneurons in the spinal nucleus of the bulbocavernosus of prepubertally castrated male Mongolian gerbils following delayed treatment with testosterone
Authors: Siegford Janice Marie , Ulibarri Catherine
Published: April 2004

Sexual dimorphism in the spinal nucleus of the bulbocavernosus (SNB) of the Mongolian gerbil is achieved by two periods of postnatal increase, one in the first month after birth and one at puberty. The pubertal increase in motoneuron number is of particular interest because it occurs in a nearly adult animal. The purpose of this research was threefold. The first was to determine the response of the SNB in prepubertally castrated male gerbils receiving delayed hormone replacement as adults. Testosterone propionate (TP) treatment resulted in numbers of SNB motoneurons comparable to those seen in intact males, whereas androgen metabolites were less effective. The second purpose was to determine the latency of motoneurons to appear in response to TP. New SNB motoneurons appeared within 2 days of delayed TP replacement in prepubertally castrated males, and 16 days of treatment did not further increase SNB motoneuron numbers. The response of the motoneurons to TP appeared more rapid than the response of the bulbocavernosus (BC) muscle, scent gland, and seminal vesicles. The third purpose was to determine whether the new cells were connected to a target muscle. After 16 days of TP treatment, more motoneurons were labeled in the SNB following injection of a retrograde tract tracer into the BC muscle compared with the number seen in control animals. Thus, new motoneurons appeared in the SNB of prepubertally castrated male Mongolian gerbils within 2 days of the start of delayed TP treatment and were connected to a target within 16 days of TP treatment. J. Comp. Neurol. 473:485–495, 2004. © 2004 Wiley‐Liss, Inc.
Expression pattern of lacZ reporter gene representing connexin36 in transgenic mice
Authors: Degen Joachim , Meier Carola , Van Der Giessen Ruben S. , Söhl Goran , Petrasch‐Parwez Elisabeth , Urschel Stephanie , Dermietzel Rolf , Schilling Karl , De Zeeuw Chris I. , Willecke Klaus
Published: April 2004

Targeted deletion of the connexin36 (Cx36) gene in the mouse genome leads to visual transmission defects, weakened synchrony of rhythmic inhibitory potentials in the neocortex, and disruption of γ‐frequency network oscillations. We have generated transgenic mice in which a reporter protein consisting of the exon1 coded N‐terminal part of Cx36 fused to β‐galactosidase (N36‐β‐gal) is expressed instead of Cx36. Here, we have used these mice for a detailed analysis of the reporter gene expression. By β‐gal staining of adult retina, we found expression of the lacZ reporter gene in the ganglion cell layer, in two rows of the inner nuclear layer, and in the photoreceptor layer. In the brain, β‐gal staining was present in γ‐aminobutyric acid (GABA)ergic neurons of the cerebellar nuclei, in non‐GABAergic neurons of the inferior olive, in mitral cells of the olfactory bulb, and in parvalbumin‐positive cells of the cerebral cortex. Outside the central nervous system, N36‐β‐gal signals were detected in insulin producing β‐cells of the pancreas and in the medulla of the adrenal gland of adult Cx36+/del[LacZ] mice. This expression pattern suggests that Cx36 fulfills functional roles not only in several types of neurons in the retina and central nervous system but also in excitable cells of the pancreas and adrenal gland. J. Comp. Neurol. 473:511–525, 2004. © 2004 Wiley‐Liss, Inc.
A crustacean serotonin receptor: Cloning and distribution in the thoracic ganglia of crayfish and freshwater prawn
Authors: Sosa María A. , Spitzer Nadja , Edwards Donald H. , Baro Deborah J.
Published: April 2004

Serotonin (5‐HT) is involved in regulating important aspects of behavior and a variety of systemic physiological functions in both vertebrates and invertebrates. These functions are mediated through binding to 5‐HT receptors, of which approximately 13 have been characterized in mammals. In crustaceans, important model systems for the study of the neural basis of behaviors, 5‐HT is also linked with higher‐order behaviors, associated with different 5‐HT receptors that have been identified at the physiological and pharmacological levels. However, no crustacean 5‐HT receptors have been identified at the molecular level. We have cloned a putative 5‐HT1 receptor (5‐HT1crust) from crayfish, prawn, and spiny lobster and have raised antibodies that recognize this protein in all three organisms. 5‐HT1crust immunoreactivity (5‐HT1crustir) was observed surrounding the somata of specific groups of neurons and as punctate staining within the neuropil in all thoracic ganglia of crayfish and prawn. In the crayfish, 5‐HT1crustir was also found in boutons surrounding the first and second nerves of each ganglion and on the 5‐HT cells of T1–4. In the prawn, 5‐HT1crustir was also found in axons that project across the ganglia and along the connectives. We found examples of colocalization of 5‐HT1crust with 5‐HT, consistent with the short‐term modulatory role of 5‐HT, as well as cases of serotonergic staining in the absence of a 5‐HT1crust signal, which might imply that other 5‐HT receptors are found at these locations. We also observed receptors that did not possess counterpart 5‐HT staining, suggesting that these may also mediate long‐term neurohormonal functions of serotonin. J. Comp. Neurol. 473:526–537, 2004. © 2004 Wiley‐Liss, Inc.
Organization of connectivity of the rat presubiculum: I. Efferent projections to the medial entorhinal cortex
Authors: Honda Yoshiko , Ishizuka Norio
Published: April 2004

The organization of the laminar and topographical projections from the presubiculum to the entorhinal area was studied in the rat by anterograde labeling with Phaseolus vulgaris leucoagglutinin and retrograde labeling with horseradish peroxidase conjugated to wheat germ agglutinin. We found that the pattern of presubiculo‐entorhinal projections differs between the superficial and deep layers of the presubiculum. The superficial layers (layers II and III) of the presubiculum gave rise to bilateral projections to layers I–VI of the medial entorhinal area (MEA). Many terminals were distributed in layer III, fewer in layer II and the deep portion of layer I, and many fewer terminals in the deep layers (layers V and VI) of MEA. In contrast, the deep layers (layers V and VI) of the presubiculum gave rise to ipsilateral projections to the entorhinal area. Many axon terminals were distributed in layers V and VI of MEA and the most superficial portion of layer I of MEA, but very few in layers II and III. In addition, the ramifications in layer I extended to the lateral entorhinal area (LEA). Using two‐dimensional unfolded maps of parahippocampal cortices, we elucidated the distinct topographical relationship in the presubiculo‐entorhinal projection: 1) The septotemporal or longitudinal axis of the presubiculum corresponded to the axis on the MEA/LEA boundary, where the septal presubiculum projected toward the rhinal fissure and the temporal presubiculum projected away from the fissure. 2) The proximodistal axis of the presubiculum corresponded to the axis from the MEA/LEA boundary to the MEA/parasubiculum boundary that was virtually perpendicular to the MEA/LEA boundary, where the proximal portion of the presubiculum (close to the subiculum) projected to the region near the MEA/LEA boundary. J. Comp. Neurol. 473:463–484, 2004. © 2004 Wiley‐Liss, Inc.
Expression of Trk receptors in the oculomotor system of the adult cat
Authors: Benítez‐Temiño Beatriz , Morcuende Sara , Mentis George Z. , de la Cruz Rosa R. , Pastor Ángel M.
Published: April 2004

We examined the expression of the three Trk receptors for neurotrophins (TrkA, TrkB, and TrkC) in the extraocular motor nuclei of the adult cat by using antibodies directed against the full‐Trk proteins in combination with horseradish peroxidase retrograde tracing. The three receptors were present in all neuronal populations investigated, including abducens motoneurons and internuclear neurons, medial rectus motoneurons of the oculomotor nucleus, and trochlear motoneurons. They were also present in the vestibular and prepositus hypoglossi nuclei. TrkA, TrkB, and TrkC immunopositive cells were found in similar percentages in the oculomotor and in the trochlear nuclei. In the abducens nucleus, however, a significantly higher percentage of cells expressed TrkB than the other two receptors, among both motoneurons (81.8%) and internuclear neurons (88.4%). The percentages obtained for the three Trk receptors in identified neuronal populations pointed to the colocalization of two or three receptors in a large number of cells. We used confocal microscopy to elucidate the subcellular location of Trk receptors. In this case, abducens motoneurons and internuclear neurons were identified with antibodies against choline acetyltransferase and calretinin, respectively. We found a different pattern of staining for each neurotrophin receptor, suggesting the possibility that each receptor and its cognate ligand may use a different route for cellular signaling. Therefore, the expression of Trk receptors in oculomotor, trochlear, and abducens motoneurons, as well as abducens internuclear neurons, suggests that their associated neurotrophins may exert an influence on the normal operation of the oculomotor circuitry. The presence of multiple Trk receptors on individual cells indicates that they likely act in concert with each other to regulate distinct functions. J. Comp. Neurol. 473:538–552, 2004. Published 2004 Wiley‐Liss, Inc.
Postnatal development of dendritic spines on olfactory bulb granule cells in rats
Authors: Matsutani Shinji , Yamamoto Noboru
Published: April 2004

Postnatal morphological changes in granule cell dendritic spines and filopodia (collectively referred to as “spines/filopodia”) were examined in the rat main olfactory bulb to characterize the development of the neural circuitry for olfaction. Granule cells were labeled with a membrane dye and confocal laser scanning microscope images of labeled spines/filopodia were acquired in the following three dendritic domains: apical dendrites in the external plexiform layer, those in the granule cell layer, and basal dendrites. In all three domains the proportion of typical spines slightly increased during development, with a concomitant decrease in the proportion of “stubby” spines lacking a neck; the proportion of filopodia remained unchanged, accounting for 20–40% of all protrusions. The mean diameter and length of the spine/filopodium population were nearly constant throughout development. On the other hand, the developmental pattern of the spine/filopodium density varied markedly, depending on the domain of the dendrites. In the external plexiform layer, the density did not change remarkably during development. The density in apical dendrites in the granule cell layer increased during the initial 2 postnatal weeks, then gradually decreased. The spine/filopodium density in basal dendrites, however, continued to increase until 4 weeks of age, and then began to decrease. These results suggest that a substantial amount of input‐specific synaptic remodeling occurs in granule cells during development, which proceeds from superficial dendritic domains to deeper ones, occurring most prominently in the basal dendrites. J. Comp. Neurol. 473:553–561, 2004. © 2004 Wiley‐Liss, Inc.
Differential expression of Homer family proteins in the developing mouse brain
Authors: Shiraishi Yoko , Mizutani Akihiro , Yuasa Shigeki , Mikoshiba Katsuhiko , Furuichi Teiichi
Published: April 2004

Homer acts as a postsynaptic adaptor protein that links multiple targets, such as proteins involved in glutamate receptor signaling. We report the differential expression of the long form of Homer proteins produced from three distinctive genes during postnatal development of the mouse brain. Homer 1b/c and Cupidin/Homer 2a/b are widespread throughout the developing brain and are down‐regulated in hindbrain‐origin regions, such as the cerebellum, pons, and medulla oblongata. In contrast, Homer 3a/b is restricted to the cerebellum, hippocampus, and neonatal olfactory bulb. In the cerebellum, Homer 1b/c and Cupidin/Homer 2a/b predominate in the postsynapses of developing granule cells, whereas Homer 3a/b is concentrated in the dendritic spines of Purkinje cells and their axons. The down‐regulation of Homer 1b/c and Cupidin/Homer 2a/b is in marked contrast to the up‐regulation of Homer 3a/b between the first and the second postnatal weeks. In the hippocampus, Homer 1b/c and Cupidin/Homer 2a/b are largely located in the CA1 region and the CA1–CA2 region, respectively, whereas Homer 3a/b is largely distributed in the CA2–CA3 region and peaks around the third postnatal week. In hippocampal cell cultures, Homer 1b/c and Cupidin/Homer 2a/b are expressed in inhibitory and excitatory neurons, whereas Homer 3a/b is largely expressed in excitatory neurons but not in inhibitory neurons. In the developing olfactory bulb, Homer 1b/c and Cupidin/Homer 2a/b are up‐regulated in the granular, external plexiform, and glomerular layers, whereas Homer 3a/b drastically decreases in these regions within the first postnatal week. Cupidin/Homer 2a/b is also expressed in olfactory sensory neurons within a distinct olfactory epithelial zone and is then widely distributed to both the axons in the olfactory nerve layer and the cilia in the olfactory epithelium. These results demonstrate that Homer family members have distinct regional, cellular, and subcellular distributions in time and space during postnatal brain development. J. Comp. Neurol. 473:582–599, 2004. © 2004 Wiley‐Liss, Inc.
Relationship between morphoelectrotonic properties of motoneuron dendrites and their trajectory
Authors: Rose P.K. , Cushing S.
Published: April 2004

The distribution and geometry of the dendritic trees of spinal motoneurons obey several well‐established rules. Some of these rules are based on systematic relationships between quantitative geometrical features (e.g., total dendritic length) and the three‐dimensional trajectory followed by dendrites from their origin to their termination. Because dendritic geometry partially determines the transmission of current and voltage signals generated by synapses on the dendritic tree, our goal was to compare the efficacy of signal transmission by dendritic trajectories that followed different directions. To achieve this goal, we constructed detailed compartmental models of the dendritic trees of three intracellularly stained biventer cervicis/complexus (BCCM) motoneurons and calculated the electronic properties of 361 dendritic paths. Each trajectory was classified according to its orientation, e.g., rostral, rostral‐dorsal‐lateral. The attenuation of current and voltage signals en route to the soma was strongly related to trajectory orientation. Trajectories with similar attenuation factors formed functional subunits that were arranged in distinct domains within the ventral horn. Changes in Rm or Ri had little effect on which trajectories belonged to each functional subunit. However, differences in the efficacy of signal transmission between subunits increased during high network activity (mimicked by decreases in Rm). The most efficient subunit delivered two times more current and four times more voltage to the soma than the least efficient subunit. These results indicate that the input‐output properties of motoneurons depend on the direction of the path taken by dendrites from their origin at the cell body to their terminals. J. Comp. Neurol. 473:562–581, 2004. © 2004 Wiley‐Liss, Inc.
The α vβ 3 integrin as a tumor homing ligand for lymphocytes
Authors: Legler Daniel F. , Johnson‐Léger Caroline , Wiedle Guido , Bron Claude , Imhof Beat A.
Published: April 2004

Despite the presence of tumor‐specific effector cells in the circulation of cancer patients, the immune response of the majority of these patients is not sufficient to prevent the growth and spread of their tumors. That tumor cells can be killed in vitro by tumor‐reactive cytotoxic T cells is testimony to the fact that the tumors are not inherently resistant to T cell killing, but rather that there is a failure in immune recognition and effector cell activation. Many reasons for this failure of the body's defense system have been suggested, including the inability of tumor‐reactive lymphocytes to migrate to tumor tissue. Here we designed a strategy to improve homing of primary lymphocytes into vascularized tumors. As a homing molecule we selected the integrin α vβ 3 since it is expressed by angiogenic vascular endothelium in tumors. To promote lymphocyte adhesion to α vβ 3 we "painted" primary lymphocytes with a recombinant, glycosylphosphatidylinositol‐linked high‐affinity ligand for α vβ 3. These painted lymphocytes specifically bound to α vβ 3 in vitro and homed to vascularized, solid tumors in vivo. This novel strategy may provide a significant advance in anti‐tumor treatment such as adoptive immune therapy.
Frontline: Neuropilin‐1: a surface marker of regulatory T cells (Vol. 34(3) 2004, pp 623–630, DOI 10.1002/eji.200324799)
Authors: Bruder Dunja , Probst‐Kepper Michael , Westendorf Astrid M. , Geffers Robert , Beissert Stefan , Loser Karin , von Boehmer Harald , Buer Jan , Hansen Wiebke
Published: April 2004

CD4+CD25+ regulatory T cells (Treg cells) control immune responsiveness to a large variety of antigens. The isolation and therapeutic manipulation of Treg cells requires the use of reliable surface receptors that are selectively up‐regulated in Treg cells. On the basis of global gene expression studies, we identified neuropilin‐1 (Nrp1) as a specific surface marker for CD4+CD25+ Treg cells. Nrp1, a receptor involved in axon guidance, angiogenesis, and the activation of T cells, is constitutively expressed on the surface of CD4+CD25+ Treg cells independently of their activation status. In contrast, Nrp1 expression is down‐regulated in naive CD4+CD25‐ T cells after TCR stimulation. Furthermore, CD4+Nrp1high T cells express high levels of Foxp3 and suppress CD4+CD25‐ T cells. Thus, Nrp1 constitutes a useful surface marker to distinguish Treg cells from both naive and recently activated CD4+CD25+ non‐regulatory T cells.

Supporting information for this article is available on the WWW under http://www.wiley‐vch.de/contents/jc_2040/2004/24799_s.pdf or from the author.

In Sect. 2.1 of the original article the wrong link to Supporting information was given. The correct link is as given above.

See original article http://dx.doi.org/10.1002/eji.200324779
Electrode Reactions of Catechol at Tyrosinase‐Immobilized Latex Suspensions
Authors: Rijiravanich Patsamon , Aoki Koichi , Chen Jingyuan , Surareungchai Werasak , Somasundrum Mithran
Published: April 2004

Tyrosinase was immobilized on polystyrene latex particles in order to control amounts of the enzyme. The tyrosinase‐coated latex particles were composed of the core polystyrene and four successive coating layers: polystyrene sulfonate, polyallylamine, tyrosinase and polyallylamine again, built up by the layer‐by‐layer technique. They showed catalytic currents for the enzymatic oxidation of catechol to o‐quinone. The enzyme activity per particle was evaluated as 2.3×10−7 units from UV absorption of o‐quinone. The relation between the catalytic current and the concentration of catechol leads to a Michaelis‐Menten type kinetic equation. The layer‐by‐layer method was found to have a deactivating effect on enzyme catalysis. In spite of this, the catechol oxidation current was larger than the current from free tyrosinase at a common value of enzyme units per volume. This is ascribed to strong adsorption of the latex particles on the electrode, leading to the enhancement of the local concentration of tyrosinase.
Indirect Voltammetric Determination of Aluminum in Environmental and Biological Samples in the Presence of the Aluminum Chelating Drugs
Authors: Di Junwei , Zhang Feng , Zhang Min , Bi Shuping
Published: April 2004

A simple indirect method using aluminum chelating drugs as electroactive complexation ligands for the voltammetric determination of aluminum in environmental and biological samples on glassy carbon working electrode is studied. In the range of pH 8–9, desferrioxamine (DFO), 1,2‐dimethy‐3‐hydroxypyrid‐4‐one (Hdmp), 3‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one (Hma) and 2,3‐dihydroxypyridine (DHP) yielded good anodic peaks. It was demonstrated that the decrease of the anodic peak current of the drugs was linear with the increase of aluminum concentration. Among them, Hdmp was found the best complexible ligand and chosen for the voltammetric determination of aluminum with EDTA as chelant, which was used for masking most of the interferences. Under the optimum experimental conditions, the linear range for determination of Al by Hdmp was 5×10−7–3×10−5 mol L−1 Al(III), the detection limit was 2×10−7 mol L−1, and the relative standard deviation for 3×10−6 mol L−1 Al(III) was 2.6% (n=7). The proposed method was applied to the determination of Al in real water samples and biological samples. The Al concentration in serum samples can be measured directly without time‐consuming digestion pretreatment.
In vitro and in vivo anti‐tumoral effect of curcumin against melanoma cells
Authors: Odot Johann , Albert Philippe , Carlier Annie , Tarpin Michel , Devy Jérôme , Madoulet Claudie
Published: April 2004

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is known to be an anti‐oxidant and an anti‐inflammatory agent. It has been demonstrated recently to possess anti‐angiogenic effects and pro‐apoptotic activities against Ehrlich ascites tumor cells. In the current study, curcumin was found to be cytotoxic in vitro for B16‐R melanoma cells resistant to doxorubicin either cultivated as monolayers or grown in three‐dimensional (3‐D) cultures (spheroids). We have demonstrated that the cytotoxic effect observed in the 2 culture types can be related to the induction of programmed cell death. In our in vivo studies, we examined the effectiveness of a prophylactic immune preparation of soluble proteins from B16‐R cells, or a treatment with curcumin as soon as tumoral appearance, alone or in combination, on the murine melanoma B16‐R. The combination treatment resulted in substantial inhibition of growth of B16‐R melanoma, whereas each treatment by itself showed little effect. Moreover, animals receiving the combination therapy exhibited an enhancement of their humoral anti‐soluble B16‐R protein immune response and a significant increase in their median survival time (>82.8% vs. 48.6% and 45.7% respectively for the immunized group and the curcumin‐treated group). Our study shows that curcumin may provide a valuable tool for the development of a therapeutic combination against the melanoma. © 2004 Wiley‐Liss, Inc.
Prognostic value of soluble P‐selectin levels in colorectal cancer
Authors: Ferroni Patrizia , Roselli Mario , Martini Francesca , D'Alessandro Roberta , Mariotti Sabrina , Basili Stefania , Spila Antonella , Aloe Simona , Palmirotta Raffaele , Maggini Alda , Del Monte Girolamo , Mancini Raffaello , Graziano Franco , Cosimelli Maurizio , Guadagni Fiorella
Published: April 2004

Measurement of soluble (s) P‐selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP‐selectin in association with clinicopathological variables in 181 patients with primary (n=149) or metastatic (n=32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP‐selectin levels were higher in patients with CRC compared either to patients with benign disease (p= 0.006) or controls (p= 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP‐selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p= 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP‐selectin (regression coefficient= 0.28, p< 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP‐selectin levels had an independent prognostic role in predicting recurrent disease (HR= 2.22, p= 0.019) and mortality from CRC (HR= 3.44, p= 0.017). These results suggest that measurement of plasma sP‐selectin might represent a prognostic indicator in the management of patients with CRC. © 2004 Wiley‐Liss, Inc.
Dietary lignan intakes and risk of pre‐ and postmenopausal breast cancer
Authors: McCann Susan E. , Muti Paola , Vito Dominica , Edge Stephen B. , Trevisan Maurizio , Freudenheim Jo L.
Published: April 2004

Lignans are plant compounds metabolized in the mammalian gut to produce the phytoestrogens enterolactone and enterodiol. Because estrogens have been linked to breast cancer etiology, lignans could affect breast cancer risk through modulation of endogenous estrogen metabolism or competitive inhibition with estrogen receptors. We examined breast cancer risk and dietary lignan intake in a population‐based case‐control study of 1,122 women with primary, incident, histologically confirmed breast cancer and 2,036 controls frequency matched to cases on age and county of residence as part of the Western New York Exposures and Breast Cancer (WEB) Study. Diet was assessed with a self‐administered 104‐item food frequency questionnaire and other relevant data were collected by detailed in‐person interviews. Lignans were expressed as the sum of the dietary precursors secoisolariciresinol and matairesinol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, adjusting for age, total energy and other breast cancer risk factors. Premenopausal women in the highest quartile of dietary lignan intake had reduced breast cancer risk (OR = 0.66; 95% CI = 0.44–0.98). No association was observed between lignan intakes and postmenopausal breast cancer. Our results suggest that dietary lignans may be important in the etiology of breast cancer, particularly among premenopausal women. © 2004 Wiley‐Liss, Inc.
Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression
Authors: Kimos Martha C. , Wang Suna , Borkowski Andrew , Yang Guang‐Yu , Yang Chung S. , Perry Kellie , Olaru Andreea , Deacu Elena , Sterian Anca , Cottrell John , Papadimitriou John , Sisodia Lopa , Selaru Florin M. , Mori Yuriko , Xu Yan , Yin Jing , Abraham John M. , Meltzer Stephen J.
Published: April 2004

PCNA and esophagin have been implicated in the multistep process of carcinogenesis, but simultaneous characterization of these proteins in the early stages of esophageal neoplastic progression has yet to be undertaken. In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principally in their cell membrane portions. PCNA, in contrast, stains the nuclei of cells in the parabasal and basal layers. We examined 201 regions from 47 patients that represented different stages of esophageal neoplasia, comprising 34 areas of normal mucosa, 18 of dysplasia in squamous epithelium (DYS/SC), 39 squamous cell carcinoma (SCCA), 29 areas of Barrett's esophagus, 48 of Barrett's dysplasia (DYS/BAR) and 33 areas of adenocarcinoma (AC). The immunostaining patterns of esophagin and PCNA were evaluated and graded for level of expression. There was loss of esophagin expression in the high‐ and low‐grade dysplasias compared to normal epithelia. In the squamous dysplasias, there was more intense staining (of esophagin) in the atypical nuclei and superficial squamous epithelial cells than in the basal cells. PCNA staining was increased in intensity in the high‐grade dysplasias relative to normal basal layer cells. Combined analysis of esophagin and PCNA appears to reveal an inverse relationship between proliferation and differentiation during esophageal neoplastic progression. Moreover, this combined staining approach also offers promise for detecting esophageal cancer in early, precancerous stages. © 2004 Wiley‐Liss, Inc.
Thomsen‐Friedenreich (T) antigen expression increases sensitivity of natural killer cell lysis of cancer cells
Authors: Sotiriadis John , Shin Soon‐Cheon , Yim Daesong , Sieber David , Kim Yoon Berm
Published: April 2004

In this study, we demonstrate a correlation between T antigen expression on a panel of human carcinoma cell lines and their sensitivity to porcine NK cell lysis. Specifically, the more T antigen is expressed, the more sensitive the cancer cells are to porcine NK cell lysis. Furthermore, this correlation also exists for these cells and their ability to induce tumors in vivo. In this porcine animal model, the less T antigen is expressed, the more prolific the tumor growth in vivo and vice versa. Using the human colorectal adenocarcinoma cell line SW‐48, we used limiting dilution to clone 2 populations of cells, one expressing high and the other low levels of T antigen, clones 143 and 111, respectively. In these cloned cells, the clone that expressed more T antigen was more NK‐sensitive in vitro and weakly induced tumor growth in vivo. Inversely, the clone that expressed less T antigen clone was more NK‐resistant in vitro and grew more prolific tumors in vivo. Using soluble T antigen in a competitive inhibition assay, there was a decrease in porcine NK cell killing of the T antigen+ human cell line Colo 320HSR. Taken together, these findings suggest a novel role for T antigen in the NK cell recognition of cancer cells, specifically as markers for NK sensitivity in carcinoma cell lines. The significance of T antigens as targets for NK cell–mediated lysis is novel and identifies NK cell–T antigen interactions as potentially significant in the immunotherapy of cancer and its associated metastases. © 2004 Wiley‐Liss, Inc.
Fibronectin stimulates human lung carcinoma cell growth by inducing cyclooxygenase‐2 (COX‐2) expression
Authors: Han Shouwei , Sidell Neil , Roser‐Page Susanne , Roman Jesse
Published: April 2004

Tobacco use is the most important risk factor for the development of lung carcinoma. One characteristic shared by tobacco‐related lung diseases is altered lung connective tissue content and composition. In particular, tobacco results in increased expression of fibronectin (FN), a matrix glycoprotein implicated in lung development, injury and repair and in tumor cell invasion. We hypothesized that excessive deposition of FN in lung might promote lung carcinoma cell proliferation. Consistent with this hypothesis, we found that FN stimulated human lung carcinoma cell proliferation and diminished apoptosis in vitro, and that this effect was mediated through the integrin α5β1 and associated with upregulation of cyclooxygenase‐2 (COX‐2) mRNA and protein expression, and increased prostaglandin E2 (PGE2) biosynthesis. The stimulatory effect of FN on COX‐2 was blocked by the specific COX‐2 inhibitor NS‐398 and by inhibitors of protein kinase C (PKC), Calphostin C, and extracellular signal‐regulated kinases (Erks), PD98095. Electrophoretic mobility shift assays revealed that FN increased the nuclear binding activity of cyclic AMP response element binding protein (CREB) and CCAAT/enhancer‐binding protein (C/EBP), 2 proteins known to play important roles in the regulation of COX‐2 promoter activity. Transient transfection assays with wild‐type and mutated constructs of the human COX‐2 gene promoter revealed that the stimulatory effect of FN was prevented when either the CRE or the NF‐IL6 (C/EBP) sites were mutated. Taken together, the results indicate that FN stimulates human lung carcinoma cell proliferation and diminishes apoptosis by inducing COX‐2 gene expression and PGE2 biosynthesis. Activation of PKC and Erk and DNA‐protein interactions at CRE and NF‐IL6 (C/EBP) sites in the COX‐2 gene promoter appear to play key roles in this process. This work demonstrates that signaling through specific matrix‐binding β1 integrins (i.e., α5β1) resulting from exaggerated deposition in lung of the matrix glycoprotein fibronectin might promote lung carcinoma cell growth. © 2004 Wiley‐Liss, Inc.
Different inhibitory effect of imatinib on phosphorylation of mitogen‐activated protein kinase and Akt and on proliferation in cells expressing different types of mutant platelet‐derived growth factor receptor‐α
Authors: Ohashi Akiko , Kinoshita Kazuo , Isozaki Koji , Nishida Toshirou , Shinomura Yasuhisa , Kitamura Yukihiko , Hirota Seiichi
Published: April 2004

Most gastrointestinal stromal tumors (GISTs) have gain‐of‐function mutations of the c‐kit gene. Previously, we found 2 types of gain‐of‐function mutation of the PDGFRA gene, Val561 to Asp and Asp842 to Val, in about half of GISTs without c‐kit gene mutations. Although the inhibitory effect of imatinib on various types of activating mutant KIT has been well examined, that on the activating mutant PDGFRA has not been fully investigated. In the present study, we examined the effect of imatinib on autophosphorylation of mutant PDGFRA, phosphorylation of MAPK and of Akt and in vitro cell proliferation using murine Ba/F3 cells stably transfected with one of the 2 murine‐type mutated PDGFRA cDNAs. Imatinib almost completely inhibited autophosphorylation of mutant PDGFRA, phosphorylation of MAPK and Akt as well as in vitro cell proliferation at the concentration of 0.01 μM in cells expressing mutant PDGFRA with Val561 to Asp. However, in cells expressing mutant PDGFRA with Asp842 to Val, imatinib almost completely inhibited autophosphorylation of mutant PDGFRA and phosphorylation of MAPK and Akt at 1.0 μM. The concentration contributing to complete inhibition of in vitro cell proliferation was 10 μM. Ba/F3 cells expressing mutant PDGFRA are a good model to investigate the mechanism of cell proliferation or growth inhibition by imatinib in mutant PDGFRA‐driven cells. © 2004 Wiley‐Liss, Inc.
Nematode Community Structure along the Continental Slope off the Kenyan Coast, Western Indian Ocean
Authors: Muthumbi Agnes W. , Vanreusel Ann , Duineveld Gerard , Soetaert Karline , Vincx Magda
Published: April 2004

Metazoan meiofauna and in particular nematode densities, diversity, community structure were studied in relation to water depth (20 m, 50 m, 500 m, 1000 m and 2000 m) along four bathymetric transects in the Western Indian Ocean off the Kenyan coast. Nematode densities ranged between 276–944 ind./10 cm2, which is comparable to values from other oligotrophic areas in the world. Densities was correlated with oxygen concentrations in the overlying water, since they were lowest at mid‐depth (500–1000 m) coinciding with the minimum oxygen level. Nematode community structure (at genus level) resembles communities found in temperate slope regions, which are also characterized by a low productivity. The community structure showed correlations with sediment composition, water depth and oxygen levels in the overlying water. Sediment composition was mainly important at the shelf where nematodes separated into a silty sediment‐dwelling community with high abundances of Daptonema, Dorylaimopsis, Terschellingia and Halalaimus, and a sandy sediment‐dwelling community characterised by high abundances of Microlaimus and Halalaimus. The genera Monhystera, Acantholaimus, Sabatieria, Molgolaimus and Halalaimus dominated the slope communities. The characteristic deep‐sea taxa, the monhysterids and Acantholaimus increased in relative abundance with increasing depth, to become dominant at the lower slope (2000 m). The upper (500 m) and mid‐slope (1000 m), which coincided with the lowest oxygen concentrations, were colonised by Sabatieria, a genus that is known to inhabit suboxic sediments. Diversity at the level of the genera showed an unimodal trend along the sampled gradient, with highest values at mid‐depth (500 m). Although the oxygen minimum at mid depths is much less pronounced than in adjacent areas, the results of this study suggest an impact on the present communities.
Comparative Environmental Assessment in the Studies of Benthic Diatom, Macroinvertebrate, and Fish Communities
Authors: Passy Sophia I. , Bode Robert W. , Carlson Douglas M. , Novak Margaret A.
Published: April 2004

Community response to environmental gradients operating at hierarchical scales was assessed in studies of benthic diatoms, macroinvertebrates and fish from 44 stream sites in the New York City watershed. Hierarchical cluster analysis (TWINSPAN) of diatoms and fish partitioned the study sites into four groups, i.e., acid streams, reservoir outlets and wetland streams, large eutrophic streams, and small eutrophic streams; macroinvertebrate TWINSPAN distinguished an additional group of silty eutrophic streams. The correspondence among the three assemblage TWINSPAN groupings was moderate, ranging from 51 to 57%. The similarity across the four major group types was the highest among large eutrophic stream and acid stream assemblages, and the lowest among small eutrophic stream assemblages.

Stepwise discriminant function analysis revealed that environmental factors discriminated most effectively the diatom grouping and least effectively the fish grouping. The best environmental predictors for diatom and macroinvertebrate grouping were conductance and percent surface water, while population density was most powerful in separating the fish groups. Carbaryl was the only pesticide that correlated with macroinvertebrate grouping.

Partial redundancy analyses suggested a differential dependence of freshwater communities on the scale of the environmental factors to which they respond. The role of small‐scale habitat and habitatland cover/land use interaction steadily increased across the diatom, macroinvertebrate, and fish assemblages, whereas the effect of large‐scale land cover/land use declined.
Life Cycle, Feeding and Production of Isoptena serricornis(Pictet, 1841) (Plecoptera, Chloroperlidae)
Authors: Derka Tomáš , Tierno De Figueroa José Manuel , Krno Il'ja
Published: April 2004

Some aspects of the biology and ecology (life cycle, feeding and production) of a population of Isoptena serricornis in the Rudava River (Slovakia) are studied, reported and discussed. The life cycle is annual, with slow growth in autumn‐winter and fast growth in late summer and spring. The growth decreased two weeks before the Fall Equinox and increased two weeks after the Spring Equinox. The flight period spans from the end of May to the beginning of July. The presence of large sand particles in the gut of all studied nymphs is of note, and indicates that I. serricornis acts as a deposit‐collector species. Nymphal food is principally composed of detritus, unicellular organisms and, in nymphs of intermediate or large size, Chironomidae larvae. Adult food is composed fundamentally of different types of pollen grains. Males usually have lower food content than females. Annual production of this species (∼694–750 mg · m−2) is very high in relation to other previously studied Chloroperlidae. This is probably largely responsible for I. serricornis being one of the most abundant components of the macroinvertebrate community in its habitat in the Rudava River. A negative correlation between production and temperature was observed.
Motor unit number estimation by decomposition‐enhanced spike‐triggered averaging: Control data, test–retest reliability, and contractile level effects
Authors: Boe Shaun G. , Stashuk Daniel W. , Doherty Timothy J.
Published: April 2004

Decomposition‐enhanced spike‐triggered averaging (DE‐STA) has been developed as a method for obtaining a motor unit number estimate (MUNE). We describe the method and report control data for the first dorsal interosseous/adductor pollicis and thenar muscles and reliability in the thenar muscles. Seventeen subjects (ages 20–50 years) took part in the study. The maximum M potential was elicited with supramaximal stimulation of the ulnar or median nerve at the wrist. Surface and intramuscularly detected electromyographic signals were then collected simultaneously during mild to moderate contractions. Decomposition algorithms were used to detect and sort the individual motor unit potential (MUP) occurrences of several concurrently active motor units in the needle‐detected signals. The MUP occurrences were used as triggering sources to estimate their corresponding surface‐detected MUPs (S‐MUPs) using STA. The mean S‐MUP size was calculated and divided into the maximum M‐potential size to derive a MUNE. The MUNE values were consistent with those previously reported with other methods, and thenar MUNEs for the two trials were similar (249 ± 78 and 246 ± 90), with high test–retest reliability (r = 0.94, P < 0.05). DE‐STA thus appears to be a valid and reliable method to obtain MUNEs. Muscle Nerve 29: 693–699, 2004
Factors influencing the spontaneous reporting of adverse drug reactions—the experience of the Slovak Republic
Authors: Tisoňová J. , Szalayová A. , Kriška M. , Gibala P. , Foltán V.
Published: April 2004

The system of adverse drug reaction (ADR) monitoring in the Slovak Republic is greatly influenced by changes taking place in the current health care delivery system. Under‐reporting and reporting biases due to selective ADR reporting provide very serious problems in pharmacovigilance. In the year 2001, the number of reported ADRs increased due to reports of angiotensin converting enzyme (ACE) inhibitor‐induced cough; this coincided with limits being imposed on the use of angiotensin‐II receptor antagonists. These factors provide an example of selective ADR reporting, deforming the quality of drug safety monitoring. They also indicate that administrative strategies can significantly affect spontaneous reporting activities. Copyright © 2003 John Wiley & Sons, Ltd.
Clinical review procedures for the Antiretroviral Pregnancy Registry
Authors: Scheuerle Angela , Covington Deborah
Published: April 2004

The Antiretroviral Pregnancy Registry (APR) is an international pregnancy exposure registry designed to monitor prenatal antiretroviral medication exposures and detect any potential increase in the risk of major birth defects. The APR process imitates that of the Metropolitan Atlanta Congenital Defects Program (MACDP) modified to account for the differences in surveillance systems. The APR case definition attempts to separate prenatal and postnatal medication exposure, includes cases with multiple conditional defects only and collects cases diagnosed at later ages. Possible temporal association between defect pathogenesis and antiretroviral medication exposure includes a way to identify cases with known etiology—such as familial genetic conditions—and those with currently ambiguous pathogenesis—like hemangiomata and club feet. The APR also accounts for confounding factors like maternal alcohol use. Some defect reports automatically generate questions back to the reporter asking for more information. The APR incorporates procedures for managing and recording some of the more inconsistently reported malformations, such as microcephaly. Copyright © 2004 John Wiley & Sons, Ltd.