bluuebunny/crossref_metadata_2025 huggingface dataset:
An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet‐B radiation
Authors: Grant William B.
Published: August 2002

BACKGROUND

There are large geographic gradients in mortality rates for a number of cancers in the U.S. (e.g., rates are approximately twice as high in the northeast compared with the southwest). Risk factors such as diet fail to explain this variation. Previous studies have demonstrated that the geographic distributions for five types of cancer are related inversely to solar radiation. The purpose of the current study was to determine how many types of cancer are affected by solar radiation and how many premature deaths from cancer occur due to insufficient ultraviolet (UV)‐B radiation.

METHODS

UV‐B data for July 1992 and cancer mortality rates in the U.S. for between 1970–1994 were analyzed in an ecologic study.

RESULTS

The findings of the current study confirm previous results that solar UV‐B radiation is associated with reduced risk of cancer of the breast, colon, ovary, and prostate as well as non‐Hodgkin lymphoma. Eight additional malignancies were found to exhibit an inverse correlation between mortality rates and UV‐B radiation: bladder, esophageal, kidney, lung, pancreatic, rectal, stomach, and corpus uteri. The annual number of premature deaths from cancer due to lower UV‐B exposures was 21,700 (95% confidence interval [95% CI], 20,400–23,400) for white Americans, 1400 (95% CI, 1100–1600) for black Americans, and 500 (95% CI, 400–600) for Asian Americans and other minorities.

CONCLUSIONS

The results of the current study demonstrate that much of the geographic variation in cancer mortality rates in the U.S. can be attributed to variations in solar UV‐B radiation exposure. Thus, many lives could be extended through increased careful exposure to solar UV‐B radiation and more safely, vitamin D3 supplementation, especially in nonsummer months. Cancer 2002;94:1867–75. © 2002 American Cancer Society.

DOI 10.1002/cncr.10427
The role of diet and specific micronutrients in the etiology of oral carcinoma
Authors: Petridou Eleni , Zavras Athanasios I. , Lefatzis Dimitrios , Dessypris Nick , Laskaris George , Dokianakis George , Segas John , Douglas Chester W. , Diehl Scott R. , Trichopoulos Dimitrios
Published: August 2002

BACKGROUND

Carcinoma of the oral cavity is one of the most common cancers worldwide. Tobacco smoking and the consumption of alcoholic beverages are significant risk factors but to the authors' knowledge the role of nutrition is not adequately understood. The authors undertook an epidemiologic study of oral carcinoma occurring in Greece, where tobacco smoking and alcohol consumption are common but the incidence of the disease is among the lowest reported in Europe.

METHODS

One hundred six patients with histologically confirmed incident oral carcinoma and an equal number of control subjects matched for age and gender were studied. Dietary information was assessed through a validated extensive food frequency questionnaire and the data were analyzed using conditional logistic regression.

RESULTS

After adjustment for energy intake, tobacco smoking, and alcohol consumption, there was evidence that the consumption of cereals, fruits, dairy products, and added lipids (which in Greece are represented mostly by olive oil) was found to be associated inversely with the risk of oral carcinoma. Only with respect to meat and meat products was there adequate evidence of a positive association with the risk of oral carcinoma. Among the micronutrients studied, riboflavin, magnesium, and iron appeared to be correlated inversely with the disease.

CONCLUSIONS

Fruits, cereals, dairy products, and olive oil appear to convey protection against oral carcinoma and their effects may be mediated through higher intakes of riboflavin, iron, and magnesium. The low incidence of oral carcinoma reported in Greece may be explained in part by the higher consumption of the food groups and micronutrients that appear to protect against the disease. Cancer 2002;94:2981–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10560
Expression pattern of αCaMKII in the mouse main olfactory bulb
Authors: Zou Dong‐Jing , Greer Charles A. , Firestein Stuart
Published: August 2002

Multifunctional Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is highly enriched at synapses and has been implicated in regulating the formation and function of several sensory systems, including the visual and the somatosensory systems. Although there is evidence for CaMKII expression in the olfactory system, the cellular localization of CaMKII has not been well studied and its function remains unknown. In this study, we examined the normal expression patterns of the predominant αCaMKII in the mouse main olfactory bulb. We showed that αCaMKII expression levels were high in the olfactory bulb and were developmentally regulated. Immunoreactivity to αCaMKII was heavy in the external plexiform layer and the granule cell layer but minimal in the olfactory nerve layer and the glomerular layer. At the cellular level, αCaMKII was selectively expressed in the γ‐aminobutyric acid (GABA)ergic granule cells but not in the GABAergic periglomerular cells. Unexpectedly, αCaMKII was not detected in the glutamatergic mitral/tufted cells. At the ultrastructural level, αCaMKII immunoreactivity was positive in granule cell spines and dendrites, but negative in mitral/tufted cell dendrites. In contrast, in the piriform cortex, as in the majority of cortical regions, αCaMKII was expressed in the glutamatergic neurons but not in the GABAergic neurons. Our results set the stage for ongoing investigations of the roles of CaMKII in the formation and function of the olfactory system. J. Comp. Neurol. 443:226–236, 2002. © 2002 Wiley‐Liss, Inc.
Cellular and subcellular distribution of NMDA receptor subunit NR2b in the retina
Authors: Pourcho Roberta G. , Qin Pu , Goebel Dennis J.
Published: August 2002

Immunocytochemical studies showed the presence of staining for the N‐methyl‐D‐aspartate (NMDA)‐R2B glutamate receptor subunit at multiple sites in the cat retina. Reaction product in photoreceptor cells was localized at the inner/outer segment junction and in the axon terminals. Staining within the inner retina was limited to ganglion cells and their dendrites ramifying throughout the inner plexiform layer. These cells were seen to receive synaptic input from cone bipolar cells in both sublaminae. As with other glutamate receptor subunits, this immunoreactivity was typically confined to a single postsynaptic element at a cone bipolar dyad complex. Immunocytochemical localization of the NMDA‐R1 subunit, considered to be an essential component of functional receptors, showed a widespread distribution across the retina including all the sites where NMDA‐R2B staining was seen. Immunoprecipitation and Western blot analysis were used to confirm the presence of the NR2B receptor protein and its association with the NR1 subunit in both proximal and distal retinal layers. The findings suggest that NMDA‐R2B subunits are positioned for multiple functions within the retina. J. Comp. Neurol. 433:75–85, 2001. © 2001 Wiley‐Liss, Inc.
Leukemia inhibitory factor, interleukin‐6, and their receptors are expressed transiently in the olfactory mucosa after target ablation
Authors: Nan Bicheng , Getchell Marilyn L. , Partin James V. , Getchell Thomas V.
Published: August 2002

Removal of the synaptic targets of olfactory receptor neurons by olfactory bulb ablation results in apoptosis of olfactory receptor neurons and up‐regulation of proliferation of their progenitors. This study focuses on the expression of the neuropoietic cytokines leukemia inhibitory factor (LIF) and its receptor (LIFR) and interleukin 6 (IL‐6) and its receptor (IL‐6R) in intercellular signaling pathways in the olfactory mucosa after target ablation. Olfactory bulbectomy (OBX) resulted in several transient, early‐onset, temporally integrated events that were detected immunohistochemically. Macrophages infiltrated the olfactory epithelium (OE) by 16 hours post‐OBX. LIF expression was up‐regulated transiently at 2 days post‐OBX, when up‐regulated expression of LIFR also was detected on globose basal cells (GBCs), a subpopulation of which are immediate progenitors of olfactory receptor neurons. GBC proliferation peaked at 3–4 days post‐OBX. In the olfactory nerve (ON), LIF‐positive and IL‐6‐positive macrophage infiltration was followed by the transient up‐regulation of expression of LIFR, IL‐6, and IL‐6R in ensheathing cells by 3 days post‐OBX. The mRNAs for LIF/LIFR, IL‐6/IL‐6R, and their common signal‐transduction molecule, gp130, in olfactory‐nasal mucosa from control mice and from 3‐day post‐OBX mice were detected with reverse transcriptase‐polymerase chain reaction (RT‐PCR). Analysis of Northern blot and relative quantitative RT‐PCR demonstrated similar temporal patterns of changes in relative mRNA levels for both LIF and IL‐6, which were up‐regulated by 16 hours post‐OBX and peaked at 2–3 days post‐OBX. These data indicate that LIF from infiltrating macrophages acts as a mitogen for GBCs and that LIF from infiltrating macrophages and IL‐6 from infiltrating macrophages and ensheathing cells act as repair factors in the ON. J. Comp. Neurol. 435:60–77, 2001. © 2001 Wiley‐Liss, Inc.
Selective localization of high concentrations of F‐actin in subpopulations of dendritic spines in rat central nervous system: A three‐dimensional electron microscopic study
Authors: Capani Francisco , Martone Maryann E. , Deerinck Thomas J. , Ellisman Mark H.
Published: August 2002

Dendritic spines differ considerably in their size, shape, and internal organization between brain regions. We examined the actin cytoskeleton in dendritic spines in hippocampus (areas CA1, CA3, and dentate gyrus), neostriatum, and cerebellum at both light and electron microscopic levels by using a novel high‐resolution photoconversion method based in the high affinity of phalloidin for filamentous (F)‐actin. In all brain regions, labeling was strongest in the heads of dendritic spines, diminishing in the spine neck. The number of labeled spines varied by region. Compared with the cerebellar molecular layer and area CA3, where nearly every dendritic spine was labeled, less than half the spines were labeled in CA1, dentate gyrus, and neostriatum. Serial section reconstructions of spines in these areas indicated that phalloidin labeling was restricted to the largest and most morphologically diverse dendritic spines. The resolution of the photoconversion technique allowed us to examine the localization and organization of actin filaments in the spine. The most intense staining for actin was found in the postsynaptic density and associated with the spines internal membrane system. In mushroom‐shaped spines, F‐actin staining was particularly strong between the lamellae of the spine apparatus. Three‐dimensional reconstruction of labeled spines by using electron tomography showed that the labeled dense material was in continuity with the postsynaptic density. These results highlight differences in the actin cytoskeleton between different spine populations and provide novel information on the organization of the actin cytoskeleton in vivo. J. Comp. Neurol. 435:156–170, 2001. © 2001 Wiley‐Liss, Inc.
Structure and response patterns of olfactory interneurons in the honeybee, Apis mellifera
Authors: Abel Regina , Rybak Jürgen , Menzel Randolf
Published: August 2002

To analyze morphologic and physiological properties of olfactory interneurons in the honeybee, Apis mellifera, antennal lobe (AL) neurons were intracellularly recorded and subsequently labeled with Neurobiotin. Additional focal injections were carried out with cobalt hexamine chloride and dextran fluorescent markers. Olfactory interneurons (projection neurons, PNs) project by means of five tracts, the lateral, the median, and three mediolateral antennocerebral tracts (l‐, m‐, and ml‐ACT, respectively) to the mushroom bodies (MBs) and the protocerebral lobe (PL) of the ipsilateral protocerebrum. Uniglomerular PNs of the m‐ and l‐ACT receiving input from a single glomerulus of the AL also arborize in different regions of the AL. The vast majority of l‐ACT innervate the T1 region, whereas m‐ACT neurons arborize exclusively in the T2, T3, and T4 regions (T1‐4 : AL projection area of sensory cells from the antennae). In the calyces of the MB, uniglomerular PNs form varicosities in the basal ring and the lip region. Individual neurons of both types exhibit unequal innervation within and between the two calyces. In addition, m‐ACT fibers ramify more densely within the lip neuropil and show a higher incidence of spine‐like processes than l‐ACTs. In the PL, l‐ACTs arborize exclusively within the lateral horn, whereas some m‐ACT neurons innervate a broader region. Multiglomerular neurons of the ml‐ACT leave the AL by means of three subtracts (ml‐ACT 1–3). Two different types can be distinguished according to their protocerebral target areas: ml‐ACTs projecting to the lateral PL (LPL) and to the neuropil around the α‐lobe (tracts 2 and 3) and neurons projecting only to the LPL (tract 1). Intracellular recordings indicate that both l‐ and m‐ACT neurons respond to general odors but with different response properties, indicating that odor information is processed in parallel pathways with different functional characteristics. Just like m‐ACT neurons, ml‐ACT neurons respond to odors with complex activity patterns. Bilateral interneurons, originating in the suboesophageal ganglion, connect glomeruli of both AL, and send an axon through the m‐ACT in each hemisphere of the brain, terminating in the lip region of the calyces. These neurons respond to contact chemical stimuli. J. Comp. Neurol. 437:363–383, 2001. © 2001 Wiley‐Liss, Inc.
Ultrastructural localization of G‐proteins and the channel protein TRP2 to microvilli of rat vomeronasal receptor cells
Authors: Menco Bert Ph. M. , Carr Virginia McM. , Ezeh Patrick I. , Liman Emily R. , Yankova Maya P.
Published: August 2002

Microvilli of vomeronasal organ (VNO) sensory epithelium receptor cells project into the VNO lumen. This lumen is continuous with the outside environment. Therefore, the microvilli are believed to be the subcellular sites of VNO receptor cells that interact with incoming VNO‐targeted odors, including pheromones. Candidate molecules, which are implicated in VNO signaling cascades, are shown to be present in VNO receptor cells. However, ultrastructural evidence that such molecules are localized within the microvilli is sparse. The present study provides firm evidence that immunoreactivity for several candidate VNO signaling molecules, notably the G‐protein subunits Giα2 and Goα, and the transient receptor potential channel 2 (TRP2), is localized prominently and selectively in VNO receptor cell microvilli. Although Giα2 and Goα are localized separately in the microvilli of two cell types that are otherwise indistinguishable in their apical and microvillar morphology, the microvilli of both cell types are TRP2(+). VNO topographical distinctions were also apparent. Centrally within the VNO sensory epithelium, the numbers of receptor cells with Giα2(+) and Goα(+) microvilli were equal. However, near the sensory/non‐sensory border, cells with Giα2(+) microvilli predominated. Scattered ciliated cells in this transition zone resembled neither VNO nor main olfactory organ (MO) receptor cells and may represent the same ciliated cells as those found in the non‐sensory part of the VNO. Thus, this study shows that, analogous to the cilia of MO receptor cells, microvilli of VNO receptor cells are enriched selectively in proteins involved putatively in signal transduction. This provides important support for the role of these molecules in VNO signaling. J. Comp. Neurol. 438:468–489, 2001. © 2001 Wiley‐Liss, Inc.
Axonal secretion of reelin by cajal‐retzius cells: Evidence from comparison of normal and RelnOrl mutant mice
Authors: Derer Paul , Derer Michèle , Goffinet André
Published: August 2002

A novel secretory pathway has been identified in the study of mice homozygous for the RelnOrl mutation, a line characterised by the defective secretion of the large extracellular matrix glycoprotein Reelin. By using both light and electron microscopy, immunohistochemical studies for Reelin in these mutants identified morphological changes in their Cajal‐Retzius cells (CR cells). The CR cells of the mutant displayed the characteristic features of bipolar, tangentially elongated neurons with a dendritic proximal pole and an axonal cone at the opposite end of the soma. At either pole, cisterns of prominent rough endoplasmic reticulum (RER) were found to be rich in Reelin. However, the Reelin‐positive RER cisterns of the axonal cones were hugely dilated in homozygous RelnOrl mice as compared with their wild type counterparts. CR cell axons displayed beads throughout their length, each contained a smooth spheroidal cistern filled with Reelin‐immunoreactive fibrillar material, and were increased in number and size in RelnOrl mice. RER phenotype was rescued in the RelnAlb2 mice, a mutation in which no Reelin protein is produced. We propose that the RER dilations viewed in the RelnOrl mutation are due to the accumulation of the defective Reelin protein, and the large axonal beads in RelnOrl mice reflect the accumulation of truncated Reelin as the result of defects in its secretion. These observations point to an original, hitherto unrecognised, mechanism of secretion by bulk transport in smooth cisterns from the axonal cone into the axon, followed by secretion in the cortical marginal zone from the axonal cisterns that we have named axonal reelin reservoirs. J. Comp. Neurol. 440:136–143, 2001. © 2001 Wiley‐Liss, Inc.
Transsexual limb transplants in fiddler crabs and expression of novel sensory capabilities
Authors: Weissburg Marc J. , Derby Charles D. , Johnson Omar , Mcalvin Brian , Moffett James M.
Published: August 2002

We used transsexual limb transplants in fiddler crabs to examine how peripheral sensory structures interact with the central nervous system (CNS) to produce a sexually dimorphic behavior. Female and male chemosensory feeding claws were transplanted onto male hosts in place of nonfeeding, nonchemosensory claws. Successfully transplanted claws retain donor morphologies and contain chemosensory neurons. Neurons in successfully transplanted female feeding claws express the enhanced sensitivity to chemical cues seen in female, but not male, neurons in claws of normal animals. When chemically stimulated, the transplanted claws evoke feeding behavior not observed in normal males, even though the sensory neurons in the transplanted limb project to the host's sexually dimorphic neuropil not known to receive chemosensory input. Behavioral sensitivity is directly related to the sensitivity of peripheral neurons in the transplanted feeding claw. Thus, the interactions between peripheral neurons and their targets may restructure the CNS so that novel sensory capabilities are expressed, and this can produce sexually dimorphic behaviors. J. Comp. Neurol. 440:311–320, 2001. © 2001 Wiley‐Liss, Inc.
The conformal plate buckling equation
Authors: Chanillo Sagun , Kiessling Michael K.‐H.
Published: August 2002

The linear equation Δ2u = 1 for the infinitesimal buckling under uniform unit load of a thin elastic plate over ℝ2 has the particularly interesting nonlinear generalization Δg2u = 1, where Δg = e−2u Δ is the Laplace‐Beltrami operator for the metric g = e2ug0, with g0 the standard Euclidean metric on ℝ2. This conformal elliptic PDE of fourth order is equivalent to the nonlinear system of elliptic PDEs of second order Δu(x)+Kg(x) exp(2u(x)) = 0 and Δ Kg(x) + exp(2u(x)) = 0, with x ∈ ℝ2, describing a conformally flat surface with a Gauss curvature function Kg that is generated self‐consistently through the metric's conformal factor. We study this conformal plate buckling equation under the hypotheses of finite integral curvature ∫ Kg exp(2u)dx = κ, finite area ∫ exp(2u)dx = α, and the mild compactness condition K+ ∈ L1(B1(y)), uniformly w.r.t. y ∈ ℝ2. We show that asymptotically for |x|→∞ all solutions behave like u(x) = −(κ/2π)ln |x| + C + o(1) and K(x) = −(α/2π) ln|x| + C + o(1), with κ ∈ (2π, 4π) and
$\alpha = \sqrt{2\kappa(4\pi - \kappa)}$. We also show that for each κ ∈ (2π, 4π) there exists a K* and a radially symmetric solution pair u, K, satisfying K(u) = κ and maxK = K*, which is unique modulo translation of the origin, and scaling of x coupled with a translation of u. © 2001 John Wiley & Sons, Inc.
Redistribution strategies for portable parallel FFT: a case study
Authors: Dubey Anshu , Tessera Daniele
Published: August 2002

The best approach to parallelize multidimensional FFT algorithms has long been under debate. Distributed transposes are widely used, but they also vary in communication policies and hence performance. In this work we analyze the impact of different redistribution strategies on the performance of parallel FFT, on various machine architectures. We found that some redistribution strategies were consistently superior, while some others were unexpectedly inferior. An in‐depth investigation into the reasons for this behavior is included in this work. Copyright © 2001 John Wiley & Sons, Ltd.
Compensation methods to support cooperative applications: A case study in automated verification of schema requirements for an advanced transaction model
Authors: Spelt David , Even Susan
Published: August 2002

Compensation plays an important role in advanced transaction models, cooperative work and workflow systems. A schema designer is typically required to supply for each transaction$T$another transaction$T^{-1}$to semantically undo the effects of$T$. Little attention has been paid to the verification of the desirable properties of such operations, however. This paper demonstrates the use of a higher‐order logic theorem prover for verifying that compensating transactions return a database to its original state. It is shown how an OODB schema is translated to the language of the theorem prover so that proofs can be performed on the compensating transactions. Copyright © 2001 John Wiley & Sons, Ltd.
How neutral networks influence evolvability
Authors: Ebner Marc , Shackleton Mark , Shipman Rob
Published: August 2002

Evolutionary algorithms apply the process of variation, reproduction, and selection to look for an individual capable of solving the task at hand. In order to improve the evolvability of a population we propose to copy important characteristics of nature's search space. Desired characteristics for a genotype–phenotype mapping are described and several highly redundant genotype–phenotype mappings are analyzed in the context of a population‐based search. We show that evolvability, defined as the ability of random variations to sometimes produce improvement, is influenced by the existence of neutral networks in genotype space. Redundant mappings allow the population to spread along the network of neutral mutations and the population is quickly able to recover after a change has occurred. The extent of the neutral networks affects the interconnectivity of the search space and thereby affects evolvability. © 2002 Wiley Periodicals, Inc.
Hypnotizability, dissociation and trauma in patients with a conversion disorder: an exploratory study
Authors: Moene Franny C. , Spinhoven Philip , Hoogduin Kees , Sandyck Pieter , Roelofs Karin
Published: August 2002

Little research has been conducted on the assumed high hypnotizability of conversion patients and on their dissociative experiences. Moreover, a relation is described between trauma, dissociation, somatization, psychopathology and conversion disorder. One hundred and two patients with motor conversion symptoms were tested for hypnotizability, dissociative experiences, trauma, somatization, general level of psychopathology and physical impairment. Our sample did not have higher levels of hypnotizability but they reported more dissociative experiences than normals. The trauma subgroup had higher levels of hypnotizability and dissociative experiences, psychopathology, somatization, and physical impairment than the non‐trauma subgroup. Uncorrected for general psychopathology, the trauma category ‘otherwise’ predicted 9.6% of the variance in the hypnotizability scores. After correction, only an additional 4.2%. The trauma category ‘emotional abuse’ contributed 18.9% to the prediction of the variance in the dissociation scores. After correction for general psychopathology, which explained 67.3% of the variance, only the sum score of the trauma categories contributed an additional 3.3%. Copyright © 2001 John Wiley & Sons, Ltd.
The network behind spatio‐temporal patterns: building low‐complexity retinal models in CNN based on morphology, pharmacology and physiology
Authors: Rekeczky Csaba , Roska Botond , Nemeth Erik , Werblin Frank S.
Published: August 2002

In this paper, a vertebrate retina model is described based on a cellular neural network (CNN) architecture. Though largely built on the experience of previous studies, the CNN computational framework is considerably simplified: first‐order RC cells are used with space‐invariant nearest‐neighbour interactions only. All non‐linear synaptic connections are monotonic continuous functions of the pre‐synaptic voltage. Time delays in the interactions are continuous represented by additional first‐order cells. The modelling approach is neuromorphic in its spirit relying on both morphological and pharmacological information. However, the primary motivation lies in fitting the spatio‐temporal output of the model to the data recorded from biological cells (tiger salamander). In order to meet a low‐complexity (VLSI) implementation framework some structural simplifications have been made. Large‐neighbourhood interaction (neurons with large processes), furthermore inter‐layer signal propagation are modelled through diffusion and wave phenomena. This work presents novel CNN models for the outer and some partial models for the inner (light adapted) retina. It describes an approach that focuses on efficient parameter tuning and also makes it possible to discuss adaptation, sensitivity and robustness issues on retinal ‘image processing’ from an engineering point of view. Copyright © 2001 John Wiley & Sons, Ltd.
Measurement of MAP kinase activation by flow cytometry using phospho‐specific antibodies to MEK and ERK: Potential for pharmacodynamic monitoring of signal transduction inhibitors
Authors: Chow Sue , Patel Harshna , Hedley David W.
Published: August 2002

Cancer cells frequently show abnormal signaling via the mitogen activated protein kinase (MAP kinase) pathway due to increased activity of surface receptors for growth factors, or as a result of ras mutations. The development of potent anti‐cancer agents that target this pathway prompts the need for analytical methods that allow pharmacodynamic monitoring of drug effects in patients during early phase clinical trial. We describe such a method, based on the activation of T‐lymphocytes in undiluted peripheral blood using phorbol myristate acetate (PMA). Following rapid hypotonic lysis and formaldehyde fixation, activation of the MAP kinase pathway can then be demonstrated using phospho‐specific antibodies that recognize the activated mediators MEK or ERK, followed by surface labeling with anti‐CD3 to identify T‐lymphocytes. This method was used to investigate the effects of a MEK inhibitor, U0126, and a new raf kinase inhibitor BAY 37‐9751 in blood samples from normal donors. Dose‐dependent inhibition of pERK activation was demonstrated for both agents. Furthermore, differential effects on pMEK activation allowed the molecular targets of the two inhibitors to be distinguished. In addition to monitoring drug effects in patients during treatment with inhibitors of the MAP kinase pathway, the general methodology described in this paper has the potential for wide application to the study of signal transduction at the single cell level using flow cytometry. Cytometry (Comm. Clin. Cytometry) 46:72–78, 2001. © 2001 Wiley‐Liss, Inc.
Performance analysis and interoperability issue of consolidation algorithms in point‐to‐multipoint ABR services
Authors: Rangsinoppamas Naris , Jaruvitayakovit Tanun , Prapinmongkolkarn Prasit
Published: August 2002

In this paper we propose a performance analysis of the consolidation algorithms in point‐to‐multipoint ABR services in ATM network. We also present a new efficient consolidation algorithm, which overcomes some drawbacks of the previous works. The performance of the previous works and our proposed consolidation algorithms are analysed mathematically. General equations for calculating the response time and allowed cell rate of the source are derived. The derived equations show relatively good agreement with simulation results and can be applied for using in various network topologies. In addition, the interoperability issue in multicast available bit rate (ABR) is investigated. It is found that the branch points implemented with different consolidation algorithms can work interoperably. It is concluded from the simulation results that the performance of the point‐to‐multipoint ABR services is dominated by the most upper stream branch point (the nearest one to the source), therefore, in order to avoid the consolidation noise and get a faster response in the network, the most upper stream branch point has to be implemented with a high accuracy consolidation algorithm while the lower stream branch point(s) should be implemented with a fast response consolidation algorithm with a less degree of complexity. Copyright © 2002 John Wiley & Sons, Ltd.
Immature teratoma of the ovary on fluid cytology
Authors: Selvaggi Suzanne M. , Guidos Barbara J.
Published: August 2002

A case of an immature teratoma of the ovary in the peritoneal fluid of a 10‐yr‐old girl who presented with a pelvic mass is presented and discussed. The ThinPrep® preparation showed a few tight clusters of small tumor cells with a high nuclear/cytoplasmic ratio, round to oval nuclei with evenly distributed chromatin and one to two small distinct nucleoli, and scanty cytoplasm. The presence of immunohistochemical‐confirmed glial tissue on the cell block preparation confirmed the diagnosis of an immature ovarian teratoma. The differential diagnosis of fluid cytology is discussed. Diagn. Cytopathol. 25:411–414, 2001. © 2001 Wiley‐Liss, Inc.
Synthesis and biological studies of a new ginkgolide C derivative: Evidence that the cardioprotective effect of ginkgolides is unrelated to PAF inhibition
Authors: Pietri Sylvia , Liebgott Thibaut , Finet Jean‐Pierre , Culcasi Marcel , Billottet Ludovic , Bernard‐Henriet Christiane
Published: August 2002

Ginkgolides have been demonstrated to protect the myocardium in experimental ischemia‐reperfusion, but the extent to which this property is not related to platelet‐activating factor (PAF) inhibition remains debated. This study was undertaken to determine whether a ginkgolide devoid of any anti‐PAF activity could retain a cardioprotective activity. For this purpose, a new ginkgolide C (3) analogue, 7‐O‐(4‐methylphenyl) ginkgolide C (4), was obtained from 3 with retention of configuration, using, in the key step, a copper‐catalyzed arylation with tris‐(4‐methylphenyl) bismuth diacetate. No PAF inhibition on rabbit platelets in vitro was found for 4 up to 1.2.10–4 M. However, 4 was found a significantly better preserving agent than 3 or ginkgolide B, a potent PAF inhibitor (all drugs at 0.35 μM), on hemodynamic and metabolic (i.e., myocardial ATP contents and enzymatic activities) indices measured in rat isolated hearts undergoing ischemia‐reperfusion. The data provide additional support to a PAF‐unrelated pharmacological activity for ginkgolides. Because the water solubility of 4, estimated by high‐performance liquid chromatography analysis, was significantly lower than that of the parent molecule 3, a likely mechanism for the protective action of 4 involves its increased affinity for the myocardium, as compared to the relatively more hydrophilic 3. Drug Dev. Res. 54:191–201, 2001. © 2002 Wiley‐Liss, Inc.
Two distinct P2Y receptors are involved in purine‐ and pyrimidine‐evoked Ca2+ elevation in mammalian brain astrocytic cultures
Authors: Bolego Chiara , Centemeri Carlo , Abbracchio Maria P. , Ceruti Stefania , Cattabeni Flaminio , Jacobson Kenneth A. , Puglisi Lina , Rovati Gian Enrico , Burnstock Geoffrey , Nicosia Simonetta
Published: August 2002

ATP and 2‐methyl‐thio‐ATP (2‐Me‐SATP) increase cytosolic calcium concentrations ([Ca2+]i) in rat striatal astrocytes (Centemeri et al. [1997] Br J Pharmacol 121:1700–1706). The aim of the present study was to: (1) characterize pyrimidine‐induced [Ca2+]i increases in the same experimental system, and (2) try to identify the multiple P2Y receptor subtypes mediating Ca2+ mobilization. UDP and UTP triggered a concentration‐dependent [Ca2+]i elevation (EC50s = 0.58 μM ± 0.4 and 31 μM ± 6, respectively). Pyrimidine‐evoked [Ca2+]i elevation was solely due to mobilization from intracellular stores, because: (1) removing calcium from extracellular medium or (2) blocking its influx with Ni2+ did not modify UTP responses; (3) the store‐depleting agent thapsigargin completely abolished UTP‐evoked [Ca2+]i increments. Guanosine‐5′‐O‐(2‐thiodiphosphate) partially inhibited the UTP response, whereas pertussis toxin (PTx) had no effect. The phospholipase C inhibitor U‐73122 significantly reduced the UTP‐evoked [Ca2+]i rise. Computer‐assisted analysis indicated that the UTP and UDP responses are mediated by a single receptor, while ATP and 2‐Me‐SATP interact with two distinct receptors. The selective P2Y1 receptor antagonist MRS2179 abolished the ATP higher potency component. Sequential challenges with the same nucleotides resulted in almost complete homologous desensitization. Pre‐exposure to UTP lowered the subsequent responses to either ATP or 2‐Me‐SATP. Maximally active concentrations of UTP and ATP were not additive. In conclusion, [Ca2+]i elevation in astrocytes by purines and pyrimidines is mediated by two distinct P2Y receptors, likely the P2Y1 and P2Y6 subtypes. Drug Dev. Res. 52:122–132, 2001. © 2001 Wiley‐Liss, Inc.
Extracellular ATP activates transcription factor NFAT in mouse microglial cells
Authors: Ferrari Davide , Stroh Christopher , Wesselborg Sebastian , Di Virgilio Francesco , Schulze‐Osthoff Klaus
Published: August 2002

The effect of extracellular ATP on the activation of NFAT, an important transcription factor involved in cytokine expression, was investigated in the mouse microglial cell line N9. Incubation with ATP resulted in the potent and rapid activation of NFAT. Both NFAT1 and NFAT2 were activated by a calcineurin‐dependent pathway that required the influx of extracellular Ca2+. Inhibition of calcineurin by immunosuppressive drugs or Ca2+ chelation prevented ATP‐induced activation and nuclear translocation of NFAT. Activation of NFAT by ATP involved a P2X7 purinoreceptor‐mediated pathway. 2′,3′ ‐(4‐benzoyl)‐benzoyl‐ATP, an ATP analog with high affinity to the P2X7 receptor, was a strong agonist of NFAT activation. In addition, microglial N9 clones selected for the absence of P2X7, but still expressing the P2Y subtype, revealed no NFAT activation in response to ATP, although NFAT could be still triggered by agents increasing intracellular Ca2+. Our data therefore suggest that triggering of the P2X7 receptor by extracellular ATP is a potent mediator of transcription factor NFAT activation, and thus could be involved in early proinflammatory processes in the immune and nervous system. Drug Dev. Res. 52:213–219, 2001. © 2001 Wiley‐Liss, Inc.
Fetal handedness and head position preference: A developmental study
Authors: de Vries J.I.P. , Wimmers R.H. , Ververs I.A.P. , Hopkins B. , Savelsbergh G.J.P. , van Geijn H.P.
Published: August 2002

Hand–head contacts were observed by means of serial ultrasound recordings in 10 healthy fetuses from 12 to 38 weeks of gestational age. Contacts were distinguished as being unimanual or bimanual, and if unimanual, whether they were made with the right or left hand. Both types of contact and ones made unimanually with the right or left hand were identified at each age as to whether they were associated with a preferential head position. A strong unimanual bias was evident at each age except for Week 36. At this age, there was a bimanual bias. Unimanual contacts did not develop a lateralized preference, and neither type of contact established a stable relationship with head position. Furthermore, there was no evidence to support the suggestion that hand contact and head position codevelop to form a preferred ipsilateral synergy. Findings are discussed relative to contradictory evidence from other fetal and neonatal studies. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 171–178, 2001
Diabetic foot ulcers: a quality of life issue
Authors: Vileikyte Loretta
Published: August 2002

Foot ulcers are a serious complication of diabetes mellitus that are associated with adverse sequelae and high costs. In addition, such foot ulcers have a significant impact on quality of life (QoL). For example, the loss of mobility associated with foot ulcers affects patients' ability to perform simple, everyday tasks and to participate in leisure activities. These and other consequences of foot ulcers often lead to depression and poor QoL. Notably, several studies have shown that patients with diabetes mellitus and foot ulcers were more depressed and had poorer QoL than those who had no diabetic complications. Given the detrimental effect foot ulcers have on patients, it is essential that these foot ulcers are prevented or treated more effectively than at present. Evidence suggests that many foot ulcers can be prevented by using intensive interventions and adopting a multidisciplinary approach to treatment. In addition, preventative strategies may become more effective if new research into how patients with diabetes experience and interpret their health threats (e.g. diagnosis ‘loss of sensation’ or a foot ulcer episode) is taken into account. With regard to treatment, new options should enable ulcers to heal more quickly than with standard therapies. One area of interest is the use of growth factors. For example, recombinant platelet‐derived growth factor, in addition to good ulcer care, has been shown to improve the number of ulcers that heal and healing times significantly compared with good ulcer care alone. Other potential new treatments include the use of skin substitutes. In summary, improved preventative measures and wound treatment should reduce the potential for patients with diabetes mellitus to experience impaired QoL caused by foot ulcers. Copyright © 2001 John Wiley & Sons, Ltd.
The AGE‐receptor in the pathogenesis of diabetic complications
Authors: Vlassara Helen
Published: August 2002

Native glucose‐derived glycation derivatives (advanced glycation end products, AGE) in vascular, renal and neuronal tissues contribute to organ damage. Glycation derivatives include a number of chemically and cell‐reactive substances, also termed glycoxidation products or glycotoxins (GT). Cell‐associated AGE‐specific receptors (AGE‐Rs), AGE‐R1‐3, RAGE, as well as the scavenger receptors ScR‐II and CD‐36 that are present on vascular, renal, hemopoietic, and neuronal/glial cells, serve in the regulation of AGE uptake and removal. AGE‐Rs also modulate cell activation, growth‐related mediators, and cell proliferation, consequently influencing organ structure/function. This occurs via oxidant stress triggered via receptor‐dependent or ‐independent pathways, and leads to signal activation pathways, resulting in pro‐inflammatory responses. In susceptible individuals, the AGE‐R expression/function may be subject to environmental or gene‐related modulation, which in turn may influence tissue‐specific gene functions. In this context, altered expression and activity of AGE‐R components has recently been found in both mouse diabetes models and humans with diabetic complications. Although several gene polymorphisms are detected in most AGE‐R components, no significant correlation to diabetic complications has as yet been found. Further investigation is underway to define whether primary or secondary genetic links of pathogenic significance exist in this system. Various AGE‐binding peptides or soluble receptors have emerged as potential sequestering agents for toxic AGEs as potential therapies for diabetic complications. Copyright © 2001 John Wiley & Sons, Ltd.
Thiazolidinediones for the prevention of diabetes in the non‐obese diabetic (NOD) mouse: implications for human type 1 diabetes
Authors: Beales Philip E. , Pozzilli Paolo
Published: August 2002

Background

Thiazolidinediones (TZDs) are a recently introduced generation of drugs acting as receptor agonists to reduce insulin resistance and used currently in combination with other hypoglycaemic agents for the treatment of type 2 diabetes. In addition, TZDs possess anti‐inflammatory properties that make them of interest for reducing the T‐cell inflammation occurring in the islets in type 1 diabetes.

Methods

The action of TZD treatment on diabetes incidence in the non‐obese diabetic (NOD) mouse was studied by investigating the effect of rosiglitazone (RGL) (400 mg/kg body weight by gavage) from 3 weeks of age (soon after weaning) onwards and comparing its effect to that of troglitazone (TGL) given by the same route.

Results

We found that RGL and TGL both significantly reduced diabetes incidence by >50% in the NOD mouse compared to litter‐matched control NOD mice (p<0.05 and p<0.01, respectively). However, the withdrawal of TGL from the market due to hepatotoxicity led us to re‐analyse our data for toxic liver effects. We found that TGL was more toxic to mice than RGL (causing ten deaths as compared with one death).

Conclusion

RGL reduces diabetes incidence in the NOD mouse model of type 1 diabetes. This may be an effect resulting from its action as on inhibitor of pro‐inflammatory genes such as cytokines and metabolic proteases. Its use may be considered for trials designed to protect beta‐cell function in humans, especially in patients with latent autoimmune diabetes of adults (LADA) and also for disease prevention. Copyright © 2002 John Wiley & Sons, Ltd.
Towards a cellular and molecular understanding of neurulation
Authors: Colas Jean‐François , Schoenwolf Gary C.
Published: August 2002

Neurulation occurs during the early embryogenesis of chordates, and it results in the formation of the neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system. The goal of studies on neurulation is to understand its tissue, cellular and molecular basis, as well as how neurulation is perturbed during the formation of neural tube defects. The tissue basis of neurulation consists of a series of coordinated morphogenetic movements within the primitive streak (e.g., regression of Hensen's node) and nascent primary germ layers formed during gastrulation. Signaling occurs between Hensen's node and the nascent ectoderm, initiating neurulation by inducing the neural plate (i.e., actually, by suppressing development of the epidermal ectoderm). Tissue movements subsequently result in shaping and bending of the neural plate and closure of the neural groove. The cellular basis of the tissue movements of neurulation consists of changes in the behavior of the constituent cells; namely, changes in cell number, position, shape, size and adhesion. Neurulation, like any morphogenetic event, occurs within the milieu of generic biophysical determinants of form present in all living tissues. Such forces govern and to some degree control morphogenesis in a tissue‐autonomous manner. The molecular basis of neurulation remains largely unknown, but we suggest that neurulation genes have evolved to work in concert with such determinants, so that appropriate changes occur in the behaviors of the correct populations of cells at the correct time, maximizing the efficiency of neurulation and leading to heritable species‐ and axial‐differences in this process. In this article, we review the tissue and cellular basis of neurulation and provide strategies to determine its molecular basis. We expect that such strategies will lead to the identification in the near future of critical neurulation genes, genes that when mutated perturb neurulation in a highly specific and predictable fashion and cause neurulation defects, thereby contributing to the formation of neural tube defects. © 2001 Wiley‐Liss, Inc.
Insulin‐like growth factor I stimulates myoblast expansion and myofiber development in the limb
Authors: Mitchell Pamela J. , Johnson Sally E. , Hannon Kevin
Published: August 2002

Insulin‐like growth factor I (IGF‐I) is expressed in the anterior and posterior mesodermal cells of the developing limb. However, a definite role for IGF‐I during early limb organogenesis is unknown. To determine the inherent participation of IGF‐I during limb organ development, a retroviral delivery system (RCAS) was used to overexpress IGF‐I throughout the developing hind limb of stage 24 chicken embryos. The area of the belly of the external gastrocnemius muscle in the IGF‐I infected limb was an average of 160, 90, 70, and 80% larger than the contralateral control muscle belly, 4, 5, 6, and 7 days postinjection, respectively (all differences P < 0.01). In comparison to the contralateral control muscles, there were a significantly greater number of muscle fibers in the IGF‐I infected muscles (P < 0.05), confirming that the majority of IGF‐I–mediated muscle enlargement was due to an increase in total fiber numbers (hyperplasia). Four days postinjection, there was a 32% increase in myoblast to myofiber ratio in the muscle of injected limbs compared with the muscle in the contralateral noninjected control limbs (P < 0.05). This result demonstrates that IGF‐I acts to expand the undifferentiated myoblast population, and as a result, more myofibers subsequently develop, and the muscles expressing ectopic IGF‐I are enlarged by means of hyperplasia. There was no difference in tibiotarsus and fibula length or diameter between the IGF‐I injected and control limb, suggesting that ectopic IGF‐I expression within the mesoderm was not a nonspecific growth stimulant of all tissues of the developing limb, but specifically enhanced skeletal muscle development and growth. Ectopic IGF‐I expression had no significant effect on myostatin mRNA concentrations. Our results support a model where mesodermally expressed IGF‐I acts to regulate the number of primary myofibers, and, therefore, size of skeletal muscles, which form during the initial events of limb myogenesis. © 2001 Wiley‐Liss, Inc.
Differential effects of orthographic transparency on dyslexia: word reading difficulty for common English words
Authors: Spencer Ken
Published: August 2002

Orthographic transparency is increasingly being recognised as an important factor in determining the manifestation of dyslexic tendencies in individuals. Recent evidence has shown that normal English‐speaking children have reading deficits in the range associated with same age dyslexic German‐speaking children for less frequently used words, and English orthography has been identified as a contributing factor. Spencer (Reading (1999) 33(2), 72–77; Journal of Research in Reading (1999) 22(3), 283–292) has proposed a predictive model for English children's reading and spelling deficits, based on orthographic features. Two main factors have been identified: consistency of sound representation and inclusion of redundant letters in English words. Using new data for reading, a unified model will be discussed which incorporates measures of depth of orthographic transparency and relates these to recent positron emission tomography (PET) research. Implications for the relative frequency and severity of dyslexia in both deep and shallow orthographies is considered in the light of such studies. Copyright © 2001 John Wiley & Sons, Ltd.