bluuebunny/crossref_metadata_2025 huggingface dataset:
Recalculation of the monomer reactivity and experimental differences in emulsion and microemulsion copolymerizations of partially water‐soluble monomers
Authors: Bhawal Sumit , Devi Surekha
Published: October 2002

On the basis of the copolymerization data for the emulsion and microemulsion polymerizations of ethyl acrylate and methyl methacrylate, the monomer concentrations at the copolymerization loci were calculated, with the assumption that the sum of their concentrations at the polymerization loci was equal to unity. The equivalency of the locus and feed concentrations, as for styrene, was invalid because of the partial water solubility of both the monomers. Consequently, the locus concentration rather than the initial feed concentration was used to recalculate the monomer reactivity at the actual site of polymerization, and this was called the true reactivity ratio. The apparent reactivity ratios for emulsion and bulk polymerizations were different, whereas those for microemulsion and bulk polymerizations were similar. This difference was attributed to the mode of polymerization in the emulsions and microemulsions, leading to different copolymer compositions for similar initial feed concentrations. This was verified experimentally from the thermal properties and particle size distribution measurements. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2802–2810, 2002
Continuous emulsion polymerization of vinyl acetate. II Operation in a single Couette–Taylor vortex flow reactor using sodium lauryl sulfate as emulsifier
Authors: Xue W. , Yoshikawa K. , Oshima A. , Sato S. , Nomura M.
Published: October 2002

Continuous emulsion polymerizations of vinyl acetate were conducted at 50°C in a single continuous Couette–Taylor vortex flow reactor (CCTVFR) using sodium lauryl sulfate as emulsifier and potassium persulfate as initiator. The polymerization can be carried out very smoothly and stably, but the steady‐state monomer conversion attained in a CCTVFR is not as high as that in a plug flow reactor (PFR), but only slightly higher than that in a continuous stirred tank reactor (CSTR), even if the Taylor number is adjusted to an optimum value. Also, the effects of operating variables, such as the emulsifier, initiator, and monomer concentrations in the feed and the mean residence time on the kinetic behaviors were almost the same as those observed in a CSTR. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2755–2762, 2002
Molecular weight distribution of polyacrylonitrile produced in supercritical CO2
Authors: Teng Xin‐rong , Shao Hui‐li , Hu Xue‐chao
Published: October 2002

An effectively linear molecular weight calibration curve of polyacrylonitrile (PAN) was obtained using a copolymer standard with a single broad molecular weight distribution. The molecular weights and molecular weight distributions of PAN obtained from precipitation polymerization of acrylonitrile in supercritical CO2 were quantitated by the calibration curve. The effects of monomer concentration, initiator concentration, the CO2 pressure, and the total reaction time on the molecular weight and molecular weight distribution were studied in detail. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2338–2341, 2002
Adeno‐associated virus–mediated osteoprotegerin gene transfer protects against particulate polyethylene–induced osteolysis in a murine model
Authors: Yang Shang‐You , Mayton Lois , Wu Bin , Goater J. Jeffrey , Schwarz Edward M. , Wooley Paul H.
Published: October 2002

Objective

Osteoprotegerin (OPG), a natural negative regulator of osteoclastogenesis and bone resorption, may be a potential therapeutic agent for treatment of osteolysis‐associated prosthetic joint loosening. Using an in vivo adeno‐associated virus (AAV)–mediated gene transfer technique, this study was designed to evaluate the protective effects of OPG transgene against orthopedic wear debris–induced bone loss in a murine model of osteolysis.

Methods

Bone tissue was implanted into established pouches on BALB/c mice, followed by the introduction of ultra‐high‐molecular‐weight polyethylene (UHMWPE) particles to provoke inflammation and osteolysis. The viruses encoding human OPG gene (rAAV‐hOPG) or β‐galactosidase marker gene (rAAV‐LacZ) were injected into the air pouches, and the tissue was harvested 7 days after viral infection for histologic and molecular analyses.

Results

Successful transgene expression was confirmed by the detection of OPG by enzyme‐linked immunosorbent assay and positive X‐Gal staining of pouch tissue (LacZ). Real‐time polymerase chain reaction indicated significant diminishment of messenger RNA expression of osteoclast markers in OPG‐transduced pouches compared with rAAV‐LacZ–transduced pouches. The transduction and expression of OPG also markedly decreased the gene copies of the biologic receptor activator of nuclear factor κB. The expression of OPG in the bone‐implanted pouch reduced bone calcium release by a mean of 39% compared with the calcium release in the other 2 groups. Computerized image analysis revealed that expression of OPG significantly protected against bone collagen loss.

Conclusion

OPG gene transfer mediated by rAAV effectively protects against particulate polyethylene–induced bone resorption in this experimental model. Data suggest that gene transfer using rAAV‐OPG may be a feasible and effective therapeutic candidate to treat or prevent wear debris–associated osteolysis and aseptic loosening.
Peptide mimics of the Bowman–Birk inhibitor reactive site loop
Authors: McBride Jeffrey D. , Watson Emma M. , Brauer Arnd B. E. , Jaulent Agnès M. , Leatherbarrow Robin J.
Published: October 2002

Bowman–Birk Inhibitors (BBIs) are small highly cross‐linked proteins that typically display an almost symmetrical “double‐headed” structure. Each “head” contains an independent proteinase binding domain. The realization that one BBI molecule could form a 1:1:1 complex with two enzymes led early workers to dissect this activity. Now, after three decades of research, it has been possible to isolate the antiproteinase activity as small (∼11 residues), cyclic, synthetic peptides, which display most of the functional aspects of the protein. More recently, it has been found that these peptide fragments are not just a synthetic curiosity—a natural 14‐residue cyclic peptide (SFTI‐1), which too encapsulates the BBI inhibitory motif, is found to occur in sunflowers. This article reviews the properties of BBI‐based peptides (including SFTI‐1) and discusses the features that are important for inhibitory activity. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 79–92, 2002
Fabrication and use of a transient contractional flow device to quantify the sensitivity of mammalian and insect cells to hydrodynamic forces
Authors: Ma Ningning , Koelling Kurt W. , Chalmers Jeffrey J.
Published: October 2002

A microfluidic device was fabricated via photolithographic techniques which can create transient elongational and shear forces ranging over three orders of magnitude while still maintaining laminar flow conditions. The contractional fluid flow inside the microfluidic device was simulated with FLUENT (a computational fluid dynamics computer program) and the local deformation forces were characterized with the scalar quantity, local energy dissipation rate. The sensitivities of four cell lines (CHO, HB‐24, Sf‐9, and MCF7) were tested in the device. The results indicate that all four cell lines are able to withstand relatively intense energy dissipation rates (up to 104–105 kW/m3), which is orders of magnitude higher than the maximum local energy dissipation rates generated by impellers in bioreactors, but comparable to that associated with small bursting bubbles. While the concept that suspended animal cells are relatively robust with respect to purely hydrodynamic forces in bioprocess equipment is well known, these results quantitatively demonstrate these observations. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 428–437, 2002.
High‐performance affinity chromatography with immobilization of protein A and L‐histidine on molded monolith
Authors: Luo Quanzhou , Zou Hanfa , Zhang Qiang , Xiao Xiangzhu , Ni Jianyi
Published: October 2002

Reactive monoliths of macroporous poly(glycidyl methacrylate‐co‐ethylene dimethacrylate) have been prepared by “in‐situ” copolymerization of the monomers in the presence of porogenic diluents. Protein A and L‐histidine were immobilized on the monoliths directly or through a spacer arm, respectively. The properties of these two kinds of affinity columns were characterized, and the results showed that the columns with coupling of ligands by a spacer arm have some extent of non‐specific adsorption for bovine serum albumin. The affinity column based on the monolithic polymer support provided us with good hydrodynamic characteristic, low flow resistance, and easy preparation. These two affinity columns were used for the purification of immunoglobulin G from human serum. The purity of the purified IgG was detected by matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS). The stability of the protein A affinity column was investigated, and its performance remained invariable after half a year. The effects of the nature and the pH of the buffer system on the adsorption capacity of human IgG on histidyl affinity column were also investigated. The protein A affinity column is favorable for rapid analysis of human IgG samples. In contrast, the advantages of mild elution conditions, high stability, as well as low cost provide the histidyl column further potential possibility for fast removal of IgG from human plasma in clinical applications. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 481–489, 2002.
Pharmacokinetics of intravenous/subcutaneous Enoxaparin in patients with acute coronary syndrome undergoing percutaneous coronary interventions
Authors: Aslam Muhammad Shakil , Sundberg Steve , Sabri M. Nagui , Cooke David , Lakier Jeffrey B.
Published: October 2002

Plasma anti‐Xa activity after Enoxaparin administration in patients with acute coronary syndrome (ACS) undergoing coronary angiography and percutaneous coronary intervention (PCI) has not been well established. Patients presenting with non–ST‐elevation ACS received an initial dose (0.75 mg/kg) of Enoxaparin intravenously (IV), with subsequent doses (1 mg/kg) subcutaneously (SC) beginning 8 hr following the IV dose. Patients who underwent PCI within 4 hr of the IV dose or 8 hr of the SC dose did not receive additional Enoxaparin. All others received 0.3–0.4 mg/kg additional IV Enoxaparin at the time of PCI. All patients undergoing PCI received a glycoprotein IIb/IIIa inhibitor and clopidogrel. Mean plasma anti‐Xa activity (units/ml) 10 min and 2, 4, 6, and 8 hr after IV dose was 2.29 ± 0.39, 0.99 ± 0.29, 0.58 ± 0.14, 0.36 ± 0.13, 0.24 ± 0.11, respectively. Mean Plasma anti‐Xa activity 2, 4, 6, 8, 10, and 12 hr after SC dose was 1.01 ± 0.22, 1.13 ± 0.27, 1.1 ± 0.41, 0.84 ± 0.19, 0.62 ± 0.24, and 0.46 ± 0.21, respectively. Mean plasma anti‐Xa activity at the start and end of PCI was 1.27 ± 0.41 and 1.07 ± 0.42, respectively. In conclusion, adequate anticoagulation with Enoxaparin may be achieved within 10 min after an IV dose of 0.75 mg/kg. High‐risk ACS patients requiring urgent PCI may benefit from this approach. PCI may be performed without additional anticoagulation within 4 hr of IV or 8 hr of SC Enoxaparin. PCI 4–8 hr after IV dose or 8–12 hr after SC dose will require additional IV Enoxaparin 0.3–0.4 mg/kg to ensure therapeutic anti‐Xa activity. Cathet Cardiovasc Intervent 2002;57:187–190. © 2002 Wiley‐Liss, Inc.
Estrogen‐eluting, phosphorylcholine‐coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model
Authors: New Gishel , Moses Jeffrey W. , Roubin Gary S. , Leon Martin B. , Colombo Antonio , Iyer Sriram S. , Tio Fermin O. , Mehran Roxana , Kipshidze Nicholas
Published: October 2002

Estrogen can inhibit intimal proliferation and accelerate endothelial regeneration after angioplasty. This suggests that estrogen may prevent in‐stent restenosis. Unlike other therapies to prevent restenosis, estrogen may also not delay endothelial regrowth, thereby avoiding the risk of late stent thrombosis. The purpose of this work was to determine the effect of a 17β‐estradiol–eluting stent on neointimal formation in a porcine model. Each artery of six pigs was randomized to either a control, low‐dose, or high‐dose 17β‐estradiol–eluting stent. All animals were sacrificed at 30 days for histopathological analysis. There was a 40% reduction in intimal area in the high‐dose stents compared with control stents (2.54 ± 1.0 vs. 4.13 ± 1.1 mm2, for high dose vs. control, respectively; P < 0.05). There was complete endothelial regeneration at 30 days and similar inflammatory response to stenting on histopathology in all the stent groups. This is the first study to show that 17β‐estradiol–eluting stents are associated with reduced neointimal formation without affecting endothelial regeneration in the pig model of in‐stent restenosis. Estrogen‐coated stents may have a potential benefit in the prevention and treatment of in‐stent restenosis. Cathet Cardiovasc Intervent 2002;57:266–271. © 2002 Wiley‐Liss, Inc.
Synthesis of a novel photoresponsive axially chiral phosphine ligand containing an arylazo group and its application to palladium‐catalyzed asymmetric allylic alkylation
Authors: Kawamura Masato , Kiyotake Ryosuke , Kudo Kazuaki
Published: October 2002

Novel photoresponsive axially chiral monophosphine ligands containing azobenzene moiety were prepared and applied to a palladium‐catalyzed allylic alkylation. The reaction of rac‐1,3‐diphenyl‐2‐propenyl acetate gave the alkylated products with up to 90% enantiomeric excess. The ligand exhibited a trans to cis photoisomerization upon irradiation with UV light. Chirality 14:724–726, 2002. © 2002 Wiley‐Liss, Inc.
Novel horizontal‐bore superconducting solenoid design for quasioptical high‐field electron paramagnetic resonance
Authors: Gullá Andrea F. , Feenan Peter , Burgess Steven , Budil David E.
Published: October 2002

A horizontal‐bore magnet and cryostat design is described that is specifically adapted to high‐frequency quasioptical electron paramagnetic resonance (EPR). The magnet is an 8‐T superconducting solenoid with an auxiliary superconducting sweep coil driven by permanently mounted current leads. The performance of the sweep magnet in this configuration is demonstrated using a lithium phthalocyanine single crystal standard, which gives peak to peak first derivative linewidths down to 19 μT. The specific advantages of the horizontal‐bore swept‐field design for quasioptical EPR include improved accessibility, sensitivity, and economy of operation compared with vertical‐bore magnets. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 201–207, 2002
Cancer clinical trial recruitment
Authors: Tattersall Martin
Published: October 2002

Clinical Research Associates have assumed an expanding role in the conduct and design of clinical trial protocols. The perspectives of these health professionals are presented in the referenced articles, and implications for clinical trials are discussed.

See also pages 1577–83 and 1584–91.
Intake of dietary folate vitamers and risk of colorectal carcinoma
Authors: Konings Erik J. M. , Goldbohm R. Alexandra , Brants Henny A. M. , Saris Wim H. M. , van den Brandt Piet A.
Published: October 2002

BACKGROUND

Several studies have reported inverse associations between folate intake and colorectal carcinoma risk. Few were prospective studies and none evaluated the association between the intake of individual folate vitamers and colorectal carcinoma risk.

METHODS

The aim of the current study was to investigate the relationship between dietary folate intake and the risk of colorectal carcinoma in a large prospective cohort study in The Netherlands comprising 120,852 men and women aged 55–69 years. After 7.3 years of follow‐up, 760 colon and 411 rectal carcinoma cases were available for analysis. Data processing and analysis used the case–cohort approach. A new Dutch database was used to estimate intakes of total and individual folate vitamers.

RESULTS

Analyses adjusted for age, energy intake, family history of colorectal carcinoma, alcohol, vitamin C, iron, and dietary fiber intake yielded an inverse association between colon carcinoma risk and total dietary folate intake (rate ratio [RR]highest vs. lowest quintile, men: 0.73; 95% confidence interval [CI], 0.46–1.17, P trend = 0.03; women: 0.68; 95% CI, 0.39–1.20, P trend = 0.18). An inverse association between rectal carcinoma and total dietary folate intake was found only among men (RR highest vs. lowest quintile, men: 0.66; 95% CI, 0.35–1.21, P trend = 0.03). Analyses showed no clear difference in colorectal carcinoma risk associated with intake of different folate vitamers.

CONCLUSIONS

Dietary folate intake was related inversely to colon and male rectal carcinoma risk. Cancer 2002;95:1421–33. © 2002 American Cancer Society.

DOI 10.1002/cncr.10866
Retinoic acid signaling at sites of plasticity in the mature central nervous system
Authors: Thompson Haskell Gloria , Maynard Thomas Michael , Shatzmiller Ron Andrew , Lamantia Anthony‐Samuel
Published: October 2002

We used transgenic reporter mice to determine whether brain regions that respond to retinoic acid (RA) during development do so in maturity. We focused on two prominent sites of embryonic RA signaling: the dorsal spinal cord and the olfactory bulb. In the mature dorsal spinal cord, expression of a direct repeat 5 RA response element (DR5‐RARE) transgene is seen in interneurons in laminae I and II, as well as in ependymal cells around the central canal. In the olfactory bulb, DR5‐RARE transgene‐expressing neurons are seen in the mature granule cell and periglomerular layers, as well as in cells in the subventricular zone of the forebrain—the established source for newly generated granule and periglomerular neurons. In addition, there are transgene‐labeled neurons in a small number of other brain regions. These include the spinal trigeminal nucleus, area postrema, habenula, amygdala, and the cerebral cortex. Thus, a distinct type of RA‐mediated gene expression, detected with the DR5‐RARE reporter transgene, defines neurons, subependymal, or ependymal cells in discrete locations throughout the neuraxis. Some of these cells—particularly those in the spinal cord and olfactory bulb—are found in central nervous system regions that receive local RA signals early in development, and retain a significant amount of functional or structural plasticity in the adult. J. Comp. Neurol. 452:228–241, 2002. © 2002 Wiley‐Liss, Inc.
How Müller glial cells in macaque fovea coat and isolate the synaptic terminals of cone photoreceptors
Authors: Burris Christine , Klug Karl , Ngo Ivy Tran , Sterling Peter , Schein Stan
Published: October 2002

A cone synaptic terminal in macaque fovea releases quanta of glutamate from ∼20 active zones at a high rate in the dark. The transmitter reaches ∼500 receptor clusters on bipolar and horizontal cell processes by diffusion laterally along the terminal's 50 μm2 secretory face and ∼2 μm inward. To understand what shapes transmitter flow, we investigated from electron photomicrographs of serial sections the relationship between Müller glial processes and cone terminals. We find that each Müller cell has one substantial trunk that ascends in the outer plexiform layer below the space between the “footprints” of the terminals. We find exactly equal numbers of Müller cell trunks and foveal cone terminals, which may make the fovea particularly vulnerable to Müller cell dysfunction. The processes that emerge from the single trunk do not ensheathe a single terminal. Instead, each Müller cell partially coats two to three terminals; in turn, each terminal is completely coated by two to three Müller cells. Therefore, the Müller cells that coat one terminal also partially coat the surrounding (∼ six) terminals, creating a common environment for the cones supplying the center/surround receptive field of foveal midget bipolar and ganglion cells. Upon reaching the terminals, the trunk divides into processes that coat the terminals' sides but not their secretory faces. This glial framework minimizes glutamate transporter (EAAT1) beneath a terminal's secretory face but maximizes EAAT1 between adjacent terminals, thus permitting glutamate to diffuse locally along the secretory face and inward toward inner receptor clusters but reducing its effective spillover to neighboring terminals. J. Comp. Neurol. 453:100–111, 2002. © 2002 Wiley‐Liss, Inc.
Synaptic relationships between hair follicle afferents and neurones expressing GABA and glycine‐like immunoreactivity in the spinal cord of the rat
Authors: Watson Alan H. D. , Hughes David I. , Bazzaz Ayoub A.
Published: October 2002

γ‐Aminobutyric acid (GABA) and glycine have been implicated in the inhibition of sensory pathways in the dorsal horn of the spinal cord. The object of this study is to investigate the interactions between neurones immunoreactive for GABA and/or glycine and hair follicle afferent terminals labelled by intracellular injection with neurobiotin. GABA and glycine‐like immunoreactivity in axons and dendrites in synaptic contact with the afferent terminals was demonstrated by using a postembedding immunogold method, and serial section reconstruction was used to show the distribution and nature of these interactions in lamina III of the dorsal horn. Most afferent boutons (94%) were postsynaptic at axo‐axonic synapses: 67% of presynaptic boutons presynaptic to the afferent terminals were immunoreactive for GABA and glycine, 24% for GABA alone, and 7% for glycine alone. Only a small percentage of dendrites postsynaptic to afferent boutons appeared to belong to inhibitory interneurones: 3% were immunoreactive for GABA and glycine, 10% for glycine alone, but 87% were immunoreactive for neither antibody. Many afferent boutons were the central terminals of what appeared to be type IIb glomeruli and were involved triadic synaptic arrangements at which boutons presynaptic to an afferent terminal also made axodendritic contacts with dendrites postsynaptic to the afferent. Many of the presynaptic boutons involved in the triads were immunoreactive for GABA and glycine. Because afferent terminals do not themselves express glycine receptors (Mitchell et al. [1993] J. Neurosci. 13:2371–2381), glycine may therefore act on dendrites postsynaptic to hair follicle afferent terminals at these triads. J. Comp. Neurol. 452:367–380, 2002. © 2002 Wiley‐Liss, Inc.
The generation, propagation, and extinction of multiphases in the KdV zero‐dispersion limit
Authors: Grava Tamara , Tian Fei‐Ran
Published: October 2002

We study the multiphases in the KdV zero‐dispersion limit. These phases are governed by the Whitham equations, which are 2g + 1 quasi‐linear hyperbolic equations where g is the number of phases. We are interested in both the interaction of two single phases and the breaking of a single phase for general initial data. We analyze in detail how a double phase is generated from the interaction or breaking, how it propagates in space‐time, and how it collapses to a single phase in a finite time.

The Whitham equations are known to be integrable via a hodograph transform. The crucial step in our approach is to formulate the hodograph transform in terms of the Euler‐Poisson‐Darboux solutions. Under our scheme, the zeros of the Jacobian of the transform are given by the zeros of the Euler‐Poisson‐Darboux solution. Hence, the problem of inverting the hodograph transform to give the Whitham solution reduces to that of counting the zeros of the Euler‐Poisson‐Darboux solution. © 2002 Wiley Periodicals, Inc.
Assessment of Escherichia coli B with enhanced permeability to fluorochromes for flow cytometric assays of bacterial cell function
Authors: Herrera Guadalupe , Martinez Alicia , Blanco Manuel , O'Connor José‐Enrique
Published: October 2002

Background

Flow cytometry has become a choice methodology for microbiological research. However, functional cytometric assays in live bacteria are still limited. This is due, in part, to the cell wall impairing penetration of vital dyes in bacteria, thus imposing permeabilization procedures. These manipulations may affect cell physiology, provoke cell aggregation or lysis, and they are time‐consuming. Escherichia coli B strains have been used for mutagenic assays because of an altered lipopolysaccharide that provokes increased membrane permeability. We assessed the use of these strains as possible alternatives for flow cytometric assays to avoid the permeabilization steps.

Methods

Suspensions of E. coli K‐12 (strain AB1157) and E. coli B (strain WP2 uvrA/pKM101, denoted as strain IC188) were stained with several fluorochromes, including fluorescein isothiocyanate, propidium iodide, Nile Red, bis‐(1,3‐dibutylbarbituric acid) trimethine oxonol, hydroethidine, and dihydro‐dichlorofluorescein diacetate, under basal conditions and following permeabilization, impairment of membrane potential, inhibition of dye efflux pump, and oxidative stress. Fluorescent staining of both strains was compared by epifluorescence microscopy and flow cytometry.

Results

The E. coli B strain IC188 exhibited more efficient staining with vital fluorochromes than the E. coli K‐12 strain AB1157 and maintained a similar membrane potential. In addition, IC188 showed higher sensitivity than AB1157 to reveal oxidative stress when challenged with prooxidants.

Conclusions

E. coli B strains may be useful for biochemical and toxicological studies based on flow cytometry and fluorescence microscopy. Cytometry 49:62–69, 2002. © 2002 Wiley‐Liss, Inc.
Diffuse large B‐cell lymphoma with fibrillary matrix
Authors: Dargent Jean‐Louis , Meiers Isabelle , Lespagnard Laurence , Ma Yan , Dehou Marie‐Françoise , Verhest Alain
Published: October 2002

Diffuse large B‐cell lymphoma (DLBCL) with fibrillary matrix is an extremely rare variant of non‐Hodgkin's lymphoma (NHL) whose pathological features are poorly known. Here, we report on our experience with such a condition arising in a 71‐yr‐old woman. Our findings not only demonstrate that DLBCL with fibrillary matrix actually represents a peculiar subtype of DLBCL, but they also illustrate that the cytologic and flow cytometric features in this disorder can be deceptive enough as to mislead even the most experienced cytopathologist. Diagn. Cytopathol. 2002;27:223–226. © 2002 Wiley‐Liss, Inc.
Cholinergic abnormalities in Alzheimer's disease: are there new targets for drug development?
Authors: Fodero Lisa R. , Small David H.
Published: October 2002

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and behavioral changes. Cholinesterase inhibitors are currently the drugs of choice for the treatment of AD. However, alternatives to cholinesterase inhibitors such as muscarinic and nicotinic agonists are also being investigated for more effective treatment of AD. This review examines the role of cholinesterase inhibitors and the potential of other therapeutic agents which target nicotinic and muscarinic receptors for the treatment of AD. Drug Dev. Res. 56:369–379, 2002. © 2002 Wiley‐Liss, Inc.
Neuroprotective properties of topiramate in organotypic hippocampal cultures: implications for treatment of vascular and other dementias
Authors: Baskys Andrius , Segal Joshua , Fang Liwei
Published: October 2002

Mood stabilizers are often used in the treatment of psychosis and agitation associated with dementia. It has been shown that the antiepileptic drug topiramate (TPM) reduced brain tissue damage in a rat model of middle cerebral artery occlusion, suggesting that it may have a neuroprotective effect. We tested this possibility using confocal microscopy to measure cell death in organotypic hippocampal tissue cultures from 5–7‐day‐old Fischer 344 rats. To induce death, cultures were treated with N‐methyl‐D‐aspartate (NMDA, 50µM, 30min), kainate (KA, 1–100µm, 60min), or transferred to a fresh culture medium. Cell death was measured as propidium iodide fluorescence 24 and 48h after the insult and normalized to the maximal number of dead cells in the culture; maximal killing was achieved by exposing cultures to 4°C ambient temperature for 48h. Treatment of cultures with TPM at low concentrations (0.01–1µm) for 48 but not for 24h prior to the insult significantly increased survival. Concentrations above 1µm were ineffective. TPM (0.1µm) protected against kainate toxicity in the CA1 area, but not the CA3–4 area. TPM did not reduce cell death in the culture medium exchange model. TPM was ineffective in cultures treated with Na+ channel blocker tetrodotoxin. Pretreatment with both 0.1µm TPM and 1µm Ca2+/diacylglycerol‐dependent PKC inhibitor Gö6976 blocked the protective effect of topiramate against NMDA. These data suggest that protective action of TPM against NMDA toxicity may involve PKC activation and Na+ channel blockade and that at low doses TPM may be a clinically useful neuroprotective agent. Drug Dev. Res. 56:393–400, 2002. © 2002 Wiley‐Liss, Inc.
Development of antiinflammatory therapy for Alzheimer's disease
Authors: Aisen Paul S.
Published: October 2002

Inflammatory mechanisms are active in the Alzheimer's disease (AD) brain. Studies that range from epidemiological surveys to therapeutic trials in transgenic mice provide growing support for the theory that antiinflammatory drugs may be useful in the prevention and/or treatment of the disease. Randomized controlled trials in humans have not yet confirmed this theory. However, prevention and treatment trials continue to test specific antiinflammatory strategies for AD. Drug Dev. Res. 56:421–427, 2002. © 2002 Wiley‐Liss, Inc.
Hippocampal structure and the action of cholinomimetic drugs
Authors: Csernansky John G. , Bardgett Mark E. , Dong Hongxin , Humphrey William , Wang Lei
Published: October 2002

Cholinomimetic drugs have become the clinical standard for the treatment of patients with dementia of the Alzheimer type (DAT). However, uncertainty remains as to the proportion of patients that respond to such drugs, and how one might predict the capacity for response before treatment is begun. The thesis of the present review is that the neuroanatomical integrity of the hippocampus determines, at least in part, the capacity of DAT patients to respond to cholinomimetic drugs. Neuroimaging studies suggest that volume losses and other neuroanatomical deformities of the hippocampus are common in patients with even mild DAT. Moreover, more severe neuroanatomical deformities of the hippocampus are associated with more severe dementia symptoms and more rapid clinical decline. Animal research, including studies of cholinergic antagonists, glutamatergic antagonists, hippocampal lesions, and animals with mutant amyloid precursor protein genes, demonstrate that behavioral abnormalities similar to those found in DAT patients, especially those related to memory, are associated with hippocampal pathology. Cholinomimetic drugs, in particular, the cholinesterase inhibitors, have been shown to reverse some but not all of these behavioral abnormalities. More research is needed in DAT patients to determine whether an analysis of hippocampal structure or function can reliably predict the outcome of treatment with cholinomimetic drugs. Further work in animals is also needed to determine the limitations of cholinomimetic drugs for reversing various types of cognitive deficits, and to develop and test other pharmacological strategies for the treatment of DAT. Drug Dev. Res. 56:531–540, 2002. © 2002 Wiley‐Liss, Inc.
Caveolin expression during chondrogenesis in the avian limb
Authors: Hollins Andrew J. , Campbell Lee , Gumbleton Mark , Evans Darrell J.R.
Published: October 2002

Caveolin is the principal component and critical structural and functional element of caveolae, omega‐shaped plasmalemmal invaginations, which have been implicated in a wide range of cellular processes in several different tissues. In the present study, we have investigated both the spatial and temporal expression of caveolin proteins during chondrogenesis in the avian tibiotarsus at days 10–20 of embryonic development. By using semiquantitative Western blotting, we found that caveolin‐1 was clearly expressed in developing avian cartilage. The positive expression of caveolin‐1 in cartilage showed an upward trend of accumulation temporally, with the highest levels of expression at 20 days of development. By using immunocytochemistry, we detected all three caveolin proteins in the cells of the outer fibrous articular surface, although caveolin‐1 demonstrated the strongest and most consistent reactivity. In all cases, however, immunoreactivity appeared to be concentrated in cells facing the articular cavity. In the epiphyseal cartilage, immunocytochemistry revealed that caveolin‐1 was present in the majority of chondrocytes within all layers of the cartilage and at all stages examined. A discrete, intense band of caveolin‐1 immunoreactivity was apparent within the layer of flattened cells immediately underlying the proliferating rounded chondrocytes and suggests that caveolin‐1 might be involved in regulating the progression of cells through these gradually maturing cell layers. In contrast to the results for caveolin‐1, in the case of caveolin‐2 and ‐3, chondrocytes were devoid of immunoreactivity in all regions of the epiphyseal cartilage. Overall, this study demonstrates that caveolin‐1, ‐2, and ‐3 are expressed during chondrogenesis in the developing avian limb, although the patterns of expression are restricted both spatially and temporally throughout the differentiating cell layers of the cartilage. The results suggest that caveolin proteins might play a differentiation‐dependent role during avian chondrogenesis. © 2002 Wiley‐Liss, Inc.
Misregulation of gene expression in the redox‐sensitive NF‐κb‐dependent limb outgrowth pathway by thalidomide
Authors: Hansen Jason M. , Gong Siew‐Ging , Philbert Martin , Harris Craig
Published: October 2002

Thalidomide is known to induce oxidative stress, but mechanisms have not been described through which oxidative stress could contribute to thalidomide‐induced terata. Oxidative stress modulates intracellular glutathione (GSH) and redox status and can perturb redox‐sensitive processes, such as transcription factor activation and/or binding. Nuclear factor‐kappa B (NF‐κB), a redox‐sensitive transcription factor involved in limb outgrowth, may be modulated by thalidomide‐induced redox shifts. Thalidomide‐resistant Sprague‐Dawley rat embryos (gestation day [GD] 13) treated with thalidomide in utero showed no changes in GSH distribution in the limb but thalidomide‐sensitive New Zealand White rabbit embryos (GD 12) showed selective GSH depletion in the limb bud progress zone (PZ). NF‐κB and regulatory genes that initiate and maintain limb outgrowth and development, such as Twist and Fgf‐10, are selectively expressed in the PZ. Green fluorescent protein (GFP) reporter vectors containing NF‐κB binding promoter sites were transfected into both rat and rabbit limb bud cells (LBCs). Treatment with thalidomide caused a preferential decrease in GFP expression in rabbit LBCs but not in rat LBCs. N‐acetylcysteine and α‐N‐t‐phenylbutyl nitrone (PBN), a free radical trapping agent, rescued GFP expression in thalidomide‐treated cultures compared with cultures that received thalidomide only. In situ hybridization showed a preferential decrease in Twist, Fgf‐8, and Fgf‐10 expression after thalidomide treatment (400 mg/kg per day) in rabbit embryos. Expression in rat embryos was not affected. Intravenous cotreatment with PBN and thalidomide (gavage) in rabbits restored normal patterns and localization of Twist, Fgf‐8, and Fgf‐10 expression. These findings show that NF‐κB binding is diminished due to selective thalidomide‐induced redox changes in the rabbit, resulting in the significant attenuation of expression of genes necessary for limb outgrowth. © 2002 Wiley‐Liss, Inc.
An automated method for registration of remotely sensed images with adaptive generation of corresponding point pairs to local disparities
Authors: Yamamoto Takahiro , Hanaizumi Hiroshi
Published: October 2002

Image registration is very important in analyzing multitemporal images. We have proposed an automated method, ARTSIM (Automated Registration meThod for Satellite IMages), for generating control point pairs on multitemporal images. Since we used spatial correlation as the index of point pair correspondence, the positions and numbers of the control point pair depended on the image quality. This tended to generate fewer pairs of control points in regions having larger spatial discrepancy and to yield insufficient registration accuracy. In this paper, we propose a new method, ARTOFL (Automated Registration Technique using Optical FLow), which measures local disparities between images to be registered and generates the minimum number of control point pairs in adequate positions so as to achieve the desired accuracy of the registration. In the method, we regard the two images to be registered as sequential shots in a movie scene. Optical flow is introduced as a tool for measuring local disparities. A new control point is generated at the point having the maximum length of the optical flow vector. Since images may have severe distortion and/or temporal changes in pixel density, some compensations are required so that larger disparities yield larger optical flow vectors. These procedures are repeated until the maximum length of the optical flow vector falls below a threshold, so that the accuracy of the registration is ensured. The validity of ARTOFL was confirmed by numerical simulation and processing of real remote sensing images. ARTOFL generated fewer control point pairs but provided higher accuracy than ARTSIM. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(1): 38–47, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10034
A proposition on improvement of a heating pattern of an antenna for microwave coagulation therapy: Introduction of a coaxial‐dipole antenna
Authors: Saito Kazuyuki , Hosaka Sumie , Okabe Shin‐ya , Yoshimura Hiroyuki , Ito Koichi
Published: October 2002

Microwave coagulation therapy (MCT) has been used mainly for the treatment of hepatocellular carcinoma (small cancer in the liver). In this therapy, a thin microwave antenna is inserted into the tumor. Using microwave radiation, the tumor is heated to a high temperature (at least 60 °C) and is killed by coagulation. In the MCT antenna used at present, there is the problem that the coagulation region is elongated along the antenna insertion direction so that the normal tissue around the tumor is also heated. It is desirable to heat the vicinity of the antenna tip in a spherical manner. In order to meet this requirement, a coaxial‐dipole antenna is used and localized heating is realized. In this paper, first, by numerical analysis by the FDTD method and measurement of the SAR distribution, the usefulness of the coaxial‐dipole antenna is demonstrated. Further, by computing the current distribution on the antenna, the reason for localization of the SAR by this antenna is studied. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(1): 16–23, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10049
A design method of array antennas taking into account mutual coupling between elements: Uniform arrays consisting of parallel half‐wavelength dipoles
Authors: Nagasawa Koji , Kitoh Ryoji , Kondo Tomokazu , Hasebe Nozomu
Published: October 2002

A design method is presented for a uniform array made of half‐wavelength dipoles placed in parallel with the mutual coupling between elements taken into account. In the design, the induced electromotive force method is used. By using the variations of the input impedance and the current due to change of the element length, the desired current value is approached. In addition, the reactance component of the input impedance is suppressed. Numerical calculations by the moment method are carried out with the obtained element length. The results are confirmed and also verified by experiment. The experimental results demonstrate that the proposed design method is useful. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(1): 1–15, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10054
Compact equation of TCP throughput estimation at upgrading bottleneck link speed
Authors: Honda Yasuhiro , Kashio Jiro , Sugimori Takahiro , Kitano Fumiaki , Suzuki Hidetomo
Published: October 2002

This paper considers a network in which one of the links is the bottleneck of communication, and the speed of that link is upgraded. A simple method of calculation is proposed for the effect of the upgrading on the throughput of the TCP communication passing through the link. As the first step, a formula for the TCP communication throughput is proposed, which is a function of the mean window size of the TCP flow control, the round‐trip time, and the loss ratio of the packet. The waiting time in the router, which is the major factor determining the round‐trip time, is approximated by the M/M/1/m queue. By combining those two expressions, the change of the throughput by upgrading the link speed is calculated. In order to verify the validity of the throughput calculation and the router model, the change of the TCP communication throughput in upgrading the speed of the bottleneck link is calculated, and the result is compared to the result of actual measurement in the experimental network composed of PPP and Ethernet. It is seen that the model proposed in this paper agrees well with the actual measurement although it is simple. The method is applied to the network between Mie University and SINET. The effect of the link speed upgrading on TCP throughput is examined and verified. The result obtained in this paper is expected to be useful in the network design, in estimating the link speed required in dissolving the bottleneck. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(1): 65–73, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1147
A model for estimating the incidence of swimming‐related gastrointestinal illness as a function of water quality indicators
Authors: Wymer Larry J. , Dufour Alfred P.
Published: October 2002

Several studies have demonstrated association between illnesses, in particular gastrointestinal illness (GI), in swimmers and sewage pollution as measured by the density of indicator organisms, such as E. coli and enterococci, in recreational waters. These studies generally classify illnesses into two categories according to the subjectivity of the reported symptoms and utilize separate analyses on the incidence of total illness and the incidence of objective symptoms of gastroenteritis. Generally, non‐swimmer illness rates are available from these studies as an indicator of the background illness rates, but are not always utilized in the model. Data from two prospective epidemiological studies conducted by the U.S. EPA and evidencing relationships between the incidence of swimming‐associated GI and enterococcus or E. coli density in marine and fresh water, respectively, are used as examples. Initially, analysis of these data consisted of the linear regression of log10 enterococcus density on the difference in illness rates between swimmers and non‐swimmers. Subsequent published analysis of the marine study utilized logistic regression, but did not take background illness rates into account. Both analyses produced separate models for rates of ‘highly credible’ and total GI symptoms. The present analysis demonstrates the advantages of including the background rates and how such rates may be incorporated in a logistic regression. Published in 2002 by John Wiley & Sons, Ltd.
Kinematic response functions and dynamic stiffnesses of bridge embankments
Authors: Zhang Jian , Makris Nicos
Published: October 2002

Recognizing that soil–structure interaction affects appreciably the earthquake response of highway overcrossings, this paper compares approximate analytical solutions and finite element results to conclude on a simple procedure that allows for the estimation of the kinematic response functions and dynamic stiffnesses of approach embankments. It is shown that the shear‐wedge model yields realistic estimates for the amplification functions of typical embankments and reveals the appropriate levels of dynamic strains which are subsequently used to estimate the stiffness and damping coefficients of embankments. The shear‐wedge model is extended to a two‐dimensional model in order to calculate the transverse static stiffness of an approach embankment loaded at one end. The formulation leads to a sound closed‐form expression for the critical length, Lc, that is the ratio of the transverse static stiffness of an approach embankment and the transverse static stiffness of a unit‐width wedge. It is shown through two case studies that the transverse dynamic stiffness (‘spring’ and ‘dashpot’) of the approach embankment can be estimated with confidence by multiplying the dynamic stiffness of the unit‐width wedge with the critical length, Lc. The paper concludes that the values obtained for the transverse kinematic response function and dynamic stiffness can also be used with confidence to represent the longitudinal kinematic response function and dynamic stiffness, respectively. Copyright © 2002 John Wiley & Sons, Ltd.
Mapping approach for 3D laminar mixing simulations: application to industrial flows
Authors: Galaktionov O. S. , Anderson P. D. , Peters G. W. M. , Meijer H. E. H.
Published: October 2002

The computationally efficient mapping technique is applied to model laminar mixing in the transport section of the co‐rotating twin screw extruder. The technique uses coarse grain values to describe the mixture and exploits temporal and spatial periodicity of the flow. The mapping approach yields adequate description of the concentration fields and residence time distributions. Copyright © 2002 John Wiley & Sons, Ltd.
Vortex structure and strength of secondary flows in model aortic arches
Authors: Lin San‐Yih , Yu Zhong‐Xin
Published: October 2002

A numerical method is developed to study the flow structures in the aortic arch. The method solves the incompressible Navier–Stokes equations. It uses a third‐order upwind scheme for the convective terms and the second‐order central scheme for the viscous terms. A DDADI time integration is used for achieving fast convergence. For the unsteady solutions, the second‐order Crank–Nicolson method coupled with the diagonalized diagonal dominated alternating direction implicit scheme (DDADI) time integration are used. The numerical results show that the method is about 2.5‐order accuracy in space and 1.8‐order accuracy in time. Then the method is used to investigate the vortex structure and strength of secondary flows in the aortic arch. Four different arch geometries are constructed to see the effect of arch configuration. Many flow properties such as pressure drop, vortex strength and separation are computed and compared among the four arch models. Copyright © 2002 John Wiley & Sons, Ltd.