bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Reactions of Furo[3,2-b]pyrrole Type Aldehydes
Authors: Krutošíková Alžbeta , Dandárová Miloslava , Alföldi Juraj
Published: April 2003

The synthesis of ethyl 2-formyl-4-benzylfuro[3,2-b]pyrrole-5-carboxylate (I) is described. A series of furo[3,2-b]pyrrole-2-carbaldehyde 2,6-dialkylphenylhydrazones (IIa - IIg) and dimethylhydrazones (IIIa - IIId) were prepared. By reaction of title compounds with hydroxylammonium chloride in acetic anhydride in the presence of pyridine corresponding cyano-substituted compounds (IVa - IVd) were obtained. Alkaline hydrolysis of IVa - IVd gave Va - Vb and the reaction with sodium azide and ammonium chloride in dimethylformamide led to VIa - VId. the structure of the compounds have been proved by UV, IR, 1H and 13C NMR spectra.
The Mobility of Tryptophan and Dansyl Fluorophores in Labelled Poly(N-ethylacrylamide) and Poly(N-ethylmethacrylamide)
Authors: Mikeš František , Výprachtický Drahomír , Pecka Jan
Published: April 2003

The mobility of tryptophan fluorophore in N-butyl-Nα-acetyltryptophanamide and in side chain of labelled poly(N-ethylacrylamide) and poly(N-ethylmethacrylamide) was investigated by the fluorescence depolarization method. The mobility of the fluorophore in the low-molecular-weight model is much higher than in side chains of the polymers. Different steric hindrance by the polymer backbone can explain the higher mobility of the fluorophore in poly(N-ethylacrylamide) and in poly(N-ethylmethacrylamide). The mobility of 5-dimethylamino-1-naphthalenesulfonamide (dansyl) fluorophore in side chains of labelled poly(N-ethylmethacrylamide) in the high-viscosity range increases with increasing number of methylene groups in side chains. The low-viscosity range, the rate s of conformational changes in short side chains (n = 2 - 7) are approximately constant and significantly decrease in long side chains (n = 10, 12). The drop in the rates is probably due to intramolecular association of the long hydrophobic chains in water.
Preparation of Uniform Size Beads with Enhanced Hydrophilicity of Pore Surface, Based on Macrophorous Poly(glycidyl methacrylate-co-ethylene dimethacrylate)
Authors: Šmigol Vladimír , Švec František
Published: April 2003

Relative hydrophilicity of poly(glyceryl methacrylate-co-ethylene dimethacrylate) beads before and after modification with epichlorohydrin followed by hydrolysis has been studied. The hydrophilicity was determined from the retention of human serum albumin in a column packed with the polymers using various mobile phases. Hydrophilization dramatically decreases the extent of human serum albumin adsorption and provides beads suitable for size-exclusion HPLC of hydrophobic proteins.
Excess Volumes of Mixtures of Alkanols with Aromatic Hydrocarbons
Authors: Munk Petr , Qin Anwei , Hoffman Dolly E.
Published: April 2003

The excess volumes of twenty binary mixtures of four aromatic hydrocarbons (benzene, toluene, ethylbenzene, and p-xylene) and five linear alkanols (methanol, ethanol, 1-propanol, 1-butanol, and 1-pentanol) at 20 °C are reported. The excess volume of systems with the same alkanol increases with increasing size and number of substituents on the benzene ring. For systems with the same aromatic hydrocarbon it increases with the length of the alkanols. The dependence of ∆V/φ1ϑ2 values on composition is noticeably asymmetric. Systems with benzene as one of the component show larger ∆V/φ1ϑ2 values than other systems and systems with methanol show different compositional dependence patterns.
Autoxidative Degradation of Poly(phenylacetylene)
Authors: Vohlídal Jiří , Rédrová Dana , Pacovská Marta , Sedláček Jan
Published: April 2003

Autooxidative degradation of high molecular-weight poly(phenylacetylene) (PPhA) in solid state and in solution was studied using the size exclusion chromatography (SEC) and UV, IR, and EPR spectrometry. No degradation was observed on PPhA stored in vacuum, whereas the polymer exposed to air was found to degrade without any induction period. No evidence of a cross-linking of oxidized PPhA was observed. The degradation of PPhA was found to be: (i) practically non-influenced by an ambient, diffuse day-light; (ii) of the random type (i.e. each main-chain bond of PPhA has the same probability of being ruptured); and (iii) fast enough to influence the results of SEC measurements.
Indirect Iodination of Estrogenes via Triazenes
Authors: Protiva Jiří , Křeček Václav , Vlk Luděk , Malinová Hana , Klinotová Eva , Máca Bohumil , Urban Jiří
Published: April 2003

Triazene derivatives of estrone and estradiol in position 2 and 4 were prepared. Their reaction with sodium iodide in an acid medium afforded the corresponding iodo derivatives. The 1H, 13C NMR and mass spectra of the compound prepared are discussed.
Charge-Transfer Complexes of Some Heteroarylthiourea Derivatives with π-Acceptors
Authors: Hamed Maher M. A. , Salman Hassan M. A. , Abd-Alla Elham M. , Mahmoud Mohamed R.
Published: April 2003

Charge-transfer complexes of some heteroarylthiourea derivatives with π-accptors have been studied spectrophotometrically in CH2Cl2. Spectral data, stability constants and enthalpies of complexation are reported. From the energies of the CT transition, ionization potentials of the donors have been obtained. Effects of donor molecular structure, π-acceptor electron affinity and nature of solvent on KCT of complexes are investigated and discussed. It is deduced that the formed CT complexes are of n-π kind and of 1 : 1 stoichiometry.
Balance of One-Step Reesterification of Vegetable Oils
Authors: Skopal František
Published: April 2003

Theoretical relationships have been derived which are necessary for realization of reesterification of vegetable oils in production of biodiesel fuel on industrial scale. Using a model system of repased oil-methanol, orientational calculations and their verification have been carried out.
A Conformational Study of the Semisynthetic Ergot Alkaloid - Terguride
Authors: Hušák Michal , Kratochvíl Bohumil , Sedmera Petr , Stuchlík Josef , Jegorov Alexandr
Published: April 2003

Conformational analysis studied by 2D NMR techniques and X-ray diffraction methods are reported for the semisynthetic ergot alkaloid - terguride, in the form of free base and as the protonated species. The structure of terguride hydrogen maleate monohydrate (C20H29N4O)+(C4H3O4)- . H2O (II) was solved by direct methods and refined anisotropically to an Rvalue of 0.068 for 1 991 unique observed reflections. The title compound crystallizes in the triclinic space group P1 with lattice parameters a = 7.061(2), b = 9.205(1), c = 12.223(4) Å, α = 96.36(2), β = 107.15(2), γ = 106.67(1)°. Studies revealed that terguride monohydrate (I) and its protonized form (terguride hydrogen maleate monohydrate) possesses the identical conformations both in solutions and in the solid state - an envelope for C and Chair for D ergoline rings.
Simpson-type paradoxes, dependence, and ageing
Authors: Scarsini Marco , Spizzichino Fabio
Published: April 2003

We will state a general version of Simpson's paradox, which corresponds to the loss of some dependence properties under marginalization. We will then provide conditions under which the paradox is avoided. Finally we will relate these Simpson-type paradoxes to some well-known paradoxes concerning the loss of ageing properties when the level of information changes.
Delay in polling systems with large switch-over times
Authors: van der Mei R. D.
Published: April 2003

We study the delay in cyclic polling systems with mixtures of gated and exhaustive service, and with deterministic switch-over times. We show that, under proper scalings, the waiting-time distribution at each of the queues converges to a uniform distribution over a known interval when the switch-over times tend to infinity.
On an inequality for the normal distribution arising in bioequivalence studies
Authors: Yao Yi-Ching , Iyer Hari
Published: April 2003

For (μ,σ2) ≠ (0,1), and 0 < z < ∞, we prove that

where φ and Φ are, respectively, the p.d.f. and the c.d.f. of a standard normal random variable. This inequality is sharp in the sense that the right-hand side cannot be replaced by a larger quantity which depends only on μ and σ. In other words, for any given (μ,σ) ≠ (0,1), the infimum, over 0 < z < ∞, of the left-hand side of the inequality is equal to the right-hand side. We also point out how this inequality arises in the context of defining individual bioequivalence.
Inequalities for the score constant in matching random sequences
Authors: Chow Yunshyong , Zhang Yu
Published: April 2003

We consider a sequence matching problem involving the optimal alignment score for contiguous sequences; rewarding matches and penalizing for deletions and mismatches. Arratia and Waterman conjectured in [1] that the score constant a(μ, δ) is a strictly monotone function (i) in δ for all positive δ and (ii) in μ if 0 ≤ μ ≤ 2δ. Here we prove that (i) is true for all δ and (ii) is true for some μ.
Favorable red and black on the integers with a minimum bet
Authors: Ruth Kevin
Published: April 2003

In a superfair red and black gambling house where the player must bet at least 2 units at each stage, a gambler wishes to maximize the probability of reaching a goal integer N before reaching zero. For win probability p > 1/2, when N is even, an optimal strategy is to bet 3 units when you have 3 units or N − 3 units and to bet 2 units otherwise. When N is odd, there are two strategies which are optimal depending on the value of the win probability p. When p is smaller than a certain value, p*, the above strategy is optimal, and when p is larger than this value, the timid strategy is optimal.
Branching and tree indexed random walks on fractals
Authors: Telcs András , Wormald Nicholas C.
Published: April 2003

This paper deals with the recurrence of branching random walks on polynomially growing graphs. Amongst other things, we demonstrate the strong recurrence of tree indexed random walks determined by the resistance properties of spherically symmetric graphs. Several branching walk models are considered to show how the branching mechanism influences the recurrence behaviour.
Identifiability for non-stationary spatial structure
Authors: Perrin Olivier , Meiring Wendy
Published: April 2003

For modelling non-stationary spatial random fieldsZ= {Z(x) :x∊ℝn,n≥2} a recent method has been proposed to deform bijectively the index space so that the spatial dispersionD(x,y) = var[Z(x)-Z(y)], (x,y)∊ℝnxℝn, depends only on the Euclidean distance in the deformed space through an isotropic variogram γ. We prove uniqueness of this model in two different cases: (i) γ is strictly increasing; (ii) γ(u) is differentiable foru> 0.
Patterns of respiration in diving penguins: is the last gasp an inspired tactic?
Authors: Wilson Rory P. , Simeone Alejandro , Luna-Jorquera Guillermo , Steinfurth Antje , Jackson Sue , Fahlman Andreas
Published: April 2003

Humboldt penguins Spheniscus humboldti in captivity and free-living Magellanic penguins S. magellanicus were fitted with loggers to determine beak angles during breathing. The Humboldt penguins were also fitted with masks for determining rates of air flow during breathing. During periods of higher gas exchange requirement, Humboldt penguins opened their beaks during inspiration, where tidal volume was linearly correlated with both change in beak angle and maximum beak angle, closed them slightly during the final stages of inspiration and finally closed them during expiration. Substantial differences were apparent between individuals. Contrary to the condition proposed for most birds, our data suggest that expiration is passive during periods of high respiratory tidal volumes, and that the increased resistance of the respiratory pathway serves to slow air flow so as to maximize gas exchange in the lungs. During foraging, Magellanic penguins at the surface between dives showed similar breathing patterns but maximum beak angles were much higher and breath cycle time shorter, as would be expected for animals attempting to maximize gas exchange. Both maximum beak angle per breath and breath frequency changed systematically over the surface pause; both were initially high, then decreased to a low before rising again to a maximum just before diving. Based on known changes in tidal volume with beak angle derived from Humboldt penguins, a simple model is proposed to examine rates of gas exchange over the surface pause. This indicates that the observed patterns do not maximize the rate of transfer of oxygen over the whole of the surface pause but are rather concerned with an initial rapid accumulation of oxygen in the tissues followed by effective carbon dioxide release.
Air Transat Uses ALTITUDE to Manage Its Aircraft Routing, Crew Pairing, and Work Assignment
Authors: Desrosiers Jacques , Lasry Arielle , McInnis Daniel , Solomon Marius M. , Soumis François
Published: April 2003

Air Transat operates charter flights to vacation spots. In 1993, it had an opportunity to expand, but its manual planning and scheduling system could not support rapid growth. Air Transat acquired the airline operations management system ALTITUDE, a three-module optimization package for aircraft routing, crew pairing, and monthly work assignment. The system helped the airline to streamline planning and scheduling and to focus on its core business and expansion rather than internal operational problems. By reducing the planning cycle, increasing operational flexibility, and supporting marketing, the system helped the company to become the largest charter operator in Canada. ALTITUDE ensures cost-effective solutions by optimizing planning and scheduling problems and allowing easy interfacing among them. It saved the company an estimated eight to 12 percent of total costs during the first year and over a million dollars during the second year in operation.
Design of Operations Management Internships Across Organizations—Learning OM by Doing OM
Authors: Wouters Marc J. F. , van Donselaar Karel H.
Published: April 2003

To teach operations management (OM), we had students work full time in companies, analyzing problems and developing solutions. Fifteen students worked in different companies but on related OM topics, and we created many opportunities for them to exchange knowledge, ideas, and experiences. We organized the project around supply chains in the electrical installation industry and in the pharmaceutical industry and involved manufacturers, wholesalers, and installers or pharmacists. It was important to keep the complexity of the analyses manageable, to stimulate information exchange between the companies, and to separate analysis from negotiation over the sharing of benefits. The Supply-Chain Logistics and Information Management (SLIM) project was valuable for students and for university staff, and it helped the companies to develop and implement improvements in their supply chains.
Reengineering: A Focus on Enterprise Integration
Authors: Arora Sant , Kumar Sameer
Published: April 2003

We surveyed industries to determine what factors trigger reengineering, the nature of reengineering projects, common causes of failure, some guidelines for reducing the chances of failure, and ways to minimize losses incurred while recovering from failed projects. Improving enterprise integration is essential to improving system performance. The advances in information technology make achieving integration feasible even in very complex systems. Decision makers, instead of striving to achieve local objectives can optimize extended value-added functions that include co-related customers. They can optimize entire supply chains reaching to end customers (both internal and external). Petrinets, tools for simulating complex systems, provide a useful frames for iteratively optimizing supply chains.
Divide and Conquer: Rohm and Haas' Response to a Changing Specialty Chemicals Market
Authors: D' Alessandro Anthony J. , Baveja Alok
Published: April 2003

Rohm and Haas is caught between giant raw-material suppliers and powerful retailers at opposite ends of the supply chain. In the early 1990s, several new competitors entered the emulsions market, threatening the company's largest business unit, Polymers and Resins (P and R). P and R also faced increasing price pressure from customers and calls to improve the rate of return to corporate shareholders. In 1995, P and R formed a redesign team to examine its precepts. Over a three-year period, we aligned P and R operations around well-defined business policies, segregating products into make-to-stock and make-to-order supply channels, prioritizing customers, and serving nonstrategic customers through distributors. These changes saved millions of dollars, increased productive capacity, and transformed the business into a leaner, more disciplined operating unit.
Homozygous inactivation of NF1 gene in a patient with familial NF1 and disseminated neuroblastoma
Authors: Origone Paola , Defferrari Raffaella , Mazzocco Katia , Cunsolo Crocifissa Lo , Bernardi Bruno De , Tonini Gian Paolo
Published: April 2003

Neurofibromatosis type 1 (NF1) patients are susceptible to tumor development. In the present study we describe a child with NF1 and disseminated neuroblastoma whose death resulted from disease progression. The mother had café‐au‐lait spots suggesting a familial NF1. Neuroblastoma cells showed MYCN amplification and chromosome 1p36 deletion, common features associated with tumor progression in this malignancy. The NF1 gene displayed a germline T → C transition of intron 14 in both the proband and mother DNA. This mutation, not yet previously described, occurs in a splicing donor site and produces a new mRNA variant observed together with normal NF1 mRNA. Furthermore, the SSCP analysis of the NF1 gene in tumor cells showed a somatic deletion encompassing the intron 26 and 27b of the paternal NF1 allele. Hence, neuroblastoma cells displayed both somatic and germline mutation of the NF1 gene. Our data suggest that, although rare, neuroblastoma in patients with NF1 may display homozygous gene inactivation. © 2003 Wiley‐Liss, Inc.
Evolution of a pigmentation gene, the melanocortin‐1 receptor, in primates
Authors: Mundy N.I. , Kelly J.
Published: April 2003

The melanocortin‐1 receptor (MC1R) forms a critical switch in the production of orange/red pheomelanin and black/brown eumelanin pigments during hair development in mammals. The molecular evolution of the melanocortin‐1 receptor gene was investigated in a broad range of primate species, including several groups with large differences in distribution of orange/red and black hairs. Primate MC1R has been subject to purifying selection throughout most of its evolution, with small changes in selective constraint being detected early in primate evolution. In contrast to the situation in humans and domestic mammals, many intraspecific and intrageneric differences in primate coat color cannot be attributed to changes in the MC1R coding sequence. Nevertheless, important changes in the biochemical function of MC1R are suggested by mutations in sites of known functional importance, particularly in New World monkeys and lemurs. The evolution of the MC1R in lion tamarins is anomalous, with a combination of a high nonsynonymous to synonymous substitution rate (dN/dS) ratio, deletions, and substitutions. Am J Phys Anthropol 121:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Spacing system of the Mysore slender loris (Loris lydekkerianus lydekkerianus)
Authors: Nekaris K.A.I.
Published: April 2003

Loris lydekkerianus lydekkerianus has been shown to have a promiscuous copulatory pattern, to maintain social networks via frequent loud calls, to interact socially throughout the night with all age classes, and to sleep socially. Though these behaviors point towards a multimale social system, no study of their spacing system has yet been provided to support this view. From October 1997–August 1998, I conducted a study of the Mysore slender loris in Ayyalur, India. During 1,400 field hours, data were collected on range use of 3 adult females, 3 adult males, 1 subadult female, and 1 subadult male. Lorises slept in groups averaging 4 individuals, composed of an adult female, her offspring, and 1–2 adult and subadult males. Sleeping sites for three groups were located within 1.9 ha in the center of the study area. The minimum convex polygon in hectares encompassing each animal's range was determined, as well as overlap among home ranges of individual lorises. Average home range sizes were: adult males, 3.6 ha ± 0.09; subadult/smaller males, 1.17 ha ± 0.26; and adult and subadult females, 1.59 ha ± 0.24. Male ranges overlapped with at least 2–3 other adult males (0.72 ha ± 0.23). Female ranges overlapped slightly with at least 2 other female ranges (0.22 ha ± 0.25). Male ranges overlapped those of at least 3 females (0.82 ha ± 0.51). Patterns of home range and sleeping site support previous suggestions of a multimale social system, similar to aye ayes and some galagos. Am J Phys Anthropol 121:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Morphology and mechanical properties of polypropylene/high‐impact polystyrene blends from postconsumer plastic waste
Authors: Santana Ruth M. Campomanes , Manrich Sati
Published: April 2003

The compatibilizing effect of the triblock copolymer poly(styrene‐b‐ethylene‐co‐butylene‐b‐styrene) (SEBS) on the morphological and mechanical properties of virgin and recycled polypropylene (PP)/high‐impact polystyrene (HIPS) blends was studied, with the properties optimized for rigid composite films. The components of the blend were obtained from municipal plastic waste, PP being acquired from mineral water bottles (PPb) and HIPS from disposable cups. These materials were preground, washed only with water, dried with hot air, and ground again (PPb) or agglutinated (HIPS). Blends with three different weight ratios of PPb and HIPS (6:1, 6:2, and 6:3) were prepared, and three different concentrations of SEBS (5, 6, and 7 wt %) were used for investigations of its compatibilizing effect. Scanning electron microscopy showed that SEBS reduced the diameter of dispersed HIPS particles in the globular and fibril shapes and improved the adhesion between the disperse phase and the matrix. However, SEBS interactions with PPb and HIPS influenced the mechanical properties of the compatibilized PPb/HIPS/SEBS blends. An adequate composition of PP/HIPS, for both virgin and recycled blends, for applications in composite films with characteristics similar to those of synthetic paper was obtained with a minimal amount of SEBS and a maximal HIPS/PP ratio in the range of concentrations studied. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2861–2867, 2003
Effects of polyethylene‐grafted maleic anhydride (PE‐g‐MA) on thermal properties, morphology, and tensile properties of low‐density polyethylene (LDPE) and corn starch blends
Authors: Liu W. , Wang Y.‐J. , Sun Z.
Published: April 2003

The effects of polyethylene‐grafted maleic anhydride (PE‐g‐MA) on the thermal properties, morphology, and tensile properties of blends of low‐density polyethylene (LDPE) and corn starch were studied with a differential scanning calorimeter (DSC), scanning electron microscope (SEM), and Instron Universal Testing Machine, respectively. Corn starch–LDPE blends with different starch content and with or without the addition of PE‐g‐MA were prepared with a lab‐scale twin‐screw extruder. The crystallization temperature of LDPE–corn starch–PE‐g‐MA blends was similar to that of pure LDPE but higher than that of LDPE–corn starch blends. The interfacial properties between corn starch and LDPE were improved after PE‐g‐MA addition, as evidenced by the structure morphology revealed by SEM. The tensile strength and elongation at break of corn starch–LDPE–PE‐g‐MA blends were greater than those of LDPE–corn starch blends, and their differences became more pronounced at higher starch contents. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2904–2911, 2003
Disruption of tumor necrosis factor receptor p55 impairs collagen turnover in experimentally induced sclerodermic skin fibroblasts
Authors: Murota Hiroyuki , Hamasaki Youichiro , Nakashima Tomoki , Yamamoto Kazuo , Katayama Ichiro , Matsuyama Toshifumi
Published: April 2003

Objective

To determine the role of tumor necrosis factor receptor p55 (TNFRp55)–mediated signaling in the pathogenesis of scleroderma.

Methods

A murine model of scleroderma that closely resembles systemic sclerosis in humans was used. Wild‐type and TNFRp55‐deficient (TNFRp55−/−) mice received a subcutaneous injection of bleomycin each day. The extent of skin fibrosis was determined by measurements of the dermal thickness, as well as histologic examinations. Expression levels of fibrogenic cytokines, procollagen α1, and matrix metalloproteinase 1 (MMP‐1), MMP‐2, and MMP‐9 messenger RNA (mRNA) were analyzed, both in vivo and in vitro, by reverse transcriptase–polymerase chain reaction assay or Western blotting.

Results

TNFRp55−/− mice began to develop severe sclerotic changes of the dermis on day 3 of the subcutaneous injections of bleomycin, while wild‐type mice did not. The expression levels of fibrogenic cytokines, procollagen α1, and MMP‐2 and MMP‐9 mRNA were unaffected in the skin of both wild‐type and TNFRp55−/− mice, with or without bleomycin treatment. Induction of MMP‐1 expression was significantly inhibited in the skin from bleomycin‐treated TNFRp55−/− mice, and this phenomenon was also observed in vitro.

Conclusion

These results indicated that signaling mediated by TNFRp55 plays an essential role in MMP‐1 expression and a key role in the collagen degradation process in this murine model. This study might provide a basis for understanding the pathogenesis of scleroderma and formulating therapeutic intervention.
Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: Effect of different methods of case classification
Authors: Rasch Elizabeth K. , Hirsch Rosemarie , Paulose‐Ram Ryne , Hochberg Marc C.
Published: April 2003

Objective

To determine prevalence estimates for rheumatoid arthritis (RA) in noninstitutionalized older adults in the US. Prevalence estimates were compared using 3 different classification methods based on current classification criteria for RA.

Methods

Data from the Third National Health and Nutrition Examination Survey (NHANES‐III) were used to generate prevalence estimates by 3 classification methods in persons 60 years of age and older (n = 5,302). Method 1 applied the “n of k” rule, such that subjects who met 3 of 6 of the American College of Rheumatology (ACR) 1987 criteria were classified as having RA (data from hand radiographs were not available). In method 2, the ACR classification tree algorithm was applied. For method 3, medication data were used to augment case identification via method 2. Population prevalence estimates and 95% confidence intervals (95% CIs) were determined using the 3 methods on data stratified by sex, race/ethnicity, age, and education.

Results

Overall prevalence estimates using the 3 classification methods were 2.03% (95% CI 1.30–2.76), 2.15% (95% CI 1.43–2.87), and 2.34% (95% CI 1.66–3.02), respectively. The prevalence of RA was generally greater in the following groups: women, Mexican Americans, respondents with less education, and respondents who were 70 years of age and older.

Conclusion

The prevalence of RA in persons 60 years of age and older is ∼2%, representing the proportion of the US elderly population who will most likely require medical intervention because of disease activity. Different classification methods yielded similar prevalence estimates, although detection of RA was enhanced by incorporation of data on use of prescription medications, an important consideration in large population surveys.
Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first‐degree relatives
Authors: Ekström Karin , Hjalgrim Henrik , Brandt Lena , Baecklund Eva , Klareskog Lars , Ekbom Anders , Askling Johan
Published: April 2003

Objective

Patients with rheumatoid arthritis (RA) are at increased risk for malignant lymphomas. Both conditions display a familial aggregation, and there are reports of RA and malignant lymphomas occurring in the same families. This study was undertaken to determine the risk of malignant lymphomas in first‐degree relatives of RA patients, in order to investigate whether the increased risk of malignant lymphomas in RA could be due to genetic or environmental risk factors common to both conditions, rather than being a consequence of the rheumatic disease.

Methods

Using Swedish nationwide and population‐based registers, we identified 76,527 patients hospitalized with RA in 1964–1999 and 70,290 first‐degree relatives of a subset of these patients. These subjects were followed up for more than 3 decades, and information on cancer occurrence was recorded.

Results

Patients with RA had a significantly increased risk of malignant lymphomas (535 cases; standardized incidence ratio [SIR] 2.00, 95% confidence interval [95% CI] 1.83–2.17), which was apparent for up to 2 decades of followup. Among the first‐degree relatives without RA, no increased risk of malignant lymphomas was found overall, although modest and nonsignificantly elevated risk estimates were observed in subgroups. With respect to childhood cancer (0–14 years of age), we observed an increased risk of Hodgkin's lymphoma (5 cases; SIR 3.18, 95% CI 1.03–7.42).

Conclusion

Patients with RA are at a markedly, but possibly time‐limited, increased risk for malignant lymphomas. There is little to suggest a prominent role for coinherited or common environmental risk factors in malignant lymphomas arising in the context of RA. Instead, lymphomas complicating RA appear to be a direct consequence of the inflammation or its treatment.
The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever
Authors: Gershoni‐Baruch Ruth , Brik Riva , Zacks Nurit , Shinawi Maruan , Lidar Merav , Livneh Avi
Published: April 2003

Objective

The clinical profile in familial Mediterranean fever (FMF), including its major manifestation, amyloidosis, is influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. In this study, we analyzed the contribution of genotypes at the MEFV and SAA1 loci to disease severity and to the development of amyloidosis, and further defined the factors affecting the clinical profile of FMF.

Methods

We investigated a sample of 277 FMF patients (154 men and 123 women), including 62 patients with nephropathic amyloidosis, in whom both FMF alleles had been identified. A detailed chart review, interview, and physical examination were undertaken to determine the patients' demographic characteristics, medical history, clinical manifestations, and treatment. The disease severity score was calculated from the Tel‐Hashomer key. Genotypes at the SAA1 locus (isoforms α, β, and γ) were determined in all patients. The SAA1 13C/T polymorphism of the SAA1 promotor was analyzed in a subset of cases.

Results

The male:female ratio (154:123, or 1.3) was higher among patients with amyloidosis (40:22, or 1.8) compared with patients without amyloidosis (114:101, or 1.1). Logistic regression analysis showed that homozygosity for the M694V allele (odds ratio [OR] 4.27, 95% confidence interval [95% CI] 2.01–9.07), the presence of the SAAα/α genotype (OR 2.99, 95% CI 1.47–6.09), the occurrence of arthritis attacks (OR 2.43, 95% CI 1.17–5.06), and male sex (OR 1.73, 95% CI 0.90–3.33) were significantly and independently associated with renal amyloidosis. Disease severity was mainly influenced by MEFV mutations and was not associated with genotypes at the SAA1 locus. The SAA1 13T allele was rare, being associated mainly with the SAA γ isoform, and not related to renal amyloidosis.

Conclusion

Overall, disease severity and the development of amyloidosis in FMF are differentially affected by genetic variations within and outside the MEFV gene.
Ethnic variation in the clinical manifestations of rheumatoid arthritis: Role of HLA–DRB1 alleles
Authors: del Rincón Inmaculada , Battafarano Daniel F. , Arroyo Ramón A. , Murphy Frederick T. , Fischbach Michael , Escalante Agustín
Published: April 2003

Objective

To assess the extent of ethnic variation in the clinical expression of rheumatoid arthritis (RA) and the role of HLA–DRB1 alleles in this variation.

Methods

We assessed consecutive RA patients for joint findings, subcutaneous nodules, laboratory and radiographic findings, and treatment. We typed HLA–DRB1 alleles to identify those that contain the shared epitope (SE). We adjusted ethnic comparisons for age and sex, and tested for ethnic heterogeneity in the effect of the SE.

Results

We studied 777 RA patients, 498 of whom were women (64%), 432 were Hispanic (56%), 272 were non‐Hispanic white (NHW; 35%), 53 were African American (AA; 7%), and 20 were Asian (3%). Compared with NHW, Hispanics had significantly more tender joints (17 versus 11), more swollen joints (8 versus 7), more frequent rheumatoid factor (RF) positivity (93% versus 84%), higher erythrocyte sedimentation rate (ESR; 45 versus 36 mm/hr), and a lower number of lifetime disease‐modifying antirheumatic drugs (1.9 versus 2.5). AA were older at onset (46 versus 44 years), had less frequent subcutaneous nodules (18% versus 28%), and higher ESR (42 versus 36 mm/hour) than did NHW. Hispanics and AA were more likely than NHW to be null for the SE (odds ratio [OR] = 4.59 for AA; and OR = 1.61 for Hispanics), and less likely to have 2 SE‐carrying alleles (OR = 0.59 for Hispanics and OR = 0.25 for AA). The number of SE copies was associated with subcutaneous nodules, ESR, RF, and radiographic changes. Ethnic heterogeneity in the effect of the SE was modest.

Conclusions

There is ethnic variation in the clinical expression of RA and in both the frequency and types of SE‐carrying HLA–DRB1 alleles. Some ethnic variation in clinical findings is associated with differences in SE frequency. However, we found that the effect of the SE on the clinical features of RA varies little between ethnic groups.
Health care utilization among older adults with arthritis
Authors: Dunlop Dorothy D. , Manheim Larry M. , Song Jing , Chang Rowland W.
Published: April 2003

Objective

To evaluate the effect of arthritis on subsequent 2‐year use of health care services and out‐of‐pocket costs among older adults and determine if comorbidities or economic resources mitigate that effect.

Methods

Data were analyzed from 6,230 participants interviewed in 1993 and 1995 in the Asset and Health Dynamic Survey Among the Oldest Old (AHEAD), a national probability sample of community‐dwelling adults. Baseline arthritis status was ascertained from the report of an arthritis‐related physician's visit or a joint replacement not associated with a hip fracture. The effect of baseline arthritis on the odds of subsequent 2‐year health care utilization and high out‐of‐pocket expenses were estimated from multiple logistic regression controlling for demographic factors, comorbidity, and economic resources.

Results

Older adults with arthritis are significantly more likely to have a physician visit (odds ratio [OR] 3.0), hospital admission (OR 1.6), outpatient surgery (OR 1.3), receive home health care (OR 1.6), and have out‐of‐pocket cost >$5,000 (OR 1.6) compared with contemporaries having similar demographics (age, sex, racial/ethnic group, marital status), comorbid conditions, and economic resources (education, income, wealth, health insurance), but not reporting arthritis.

Conclusions

Older adults with symptomatic arthritis reported greater medical utilization and cost compared with people not reporting arthritis. These disparities persisted after accounting for differences in demographics, comorbidities, and economic factors. These findings document greater economic burdens on a personal and societal level among people with arthritis. As individuals, older adults with arthritis spend more out‐of‐pocket dollars for health care than their contemporaries without arthritis. On a societal level, these findings of greater health care utilization among people with arthritis point to increasing future demands on the US health care system due to demographic increases in the numbers of older adults with arthritis and support policies aimed at improving arthritis prevention and treatment as well as reducing the economic disparities between those with and without arthritis.
Evaluation of a chiral stationary phase derived from a simple Diels‐Alder reaction
Authors: Thunberg Linda , Allenmark Stig
Published: April 2003

The bicyclic, C2‐symmetric dicarboxylic acid obtained from the cycloaddition of fumaric acid to anthracene can readily be prepared in enantiomerically pure form on a large scale. Conversion of either enantiomer of the diacid into its corresponding bis‐allylamide yields a selector unit, used as a building block in the synthesis of a chiral stationary phase (CSP). The terminal C–C double bonds in the selector unit were used in a hydrosilylation reaction involving a multifunctional hydrosilane to effect polymerization, crosslinking, and immobilization to the vinyl‐silica used as support. A study of the enantiomer‐discriminating abilities of the new CSP was made. Large separation factors were obtained for a series of benzodiazepinones, which were studied in further detail by the use of different retention modifiers. To some extent, rationalization of retention data has been achieved in terms of competition for hydrogen bonding. Chirality 15:400–408, 2003. © 2003 Wiley‐Liss, Inc.
Stereoselective pharmacokinetics of flurbiprofen and formation of covalent adducts with plasma protein in adjuvant‐induced arthritic rats
Authors: Nagao Tomoaki , Tanino Tadatoshi , Iwaki Masahiro
Published: April 2003

To determine the effect of arthritis on the disposition of flurbiprofen (FP) and its acyl glucuronide (FPG) as well as formation of covalent adducts with plasma protein, a pharmacokinetic study was carried out in adjuvant‐induced arthritic (AA) rats. In control animals the pharmacokinetics of FP were stereoselective following intravenous bolus injection of rac‐FP: (–)‐(R)‐FP showed higher plasma clearance (CLtot) and shorter mean residence time (MRT) compared to (+)‐(S)‐FP. The CLtot and clearance for the glucuronide formation (CLglu) of both enantiomers in AA rats were extremely increased compared to those in control rats. Increased total clearance in AA rats was due, at least in part, to a remarkable increase in the plasma unbound fraction of FP, consistent with a decrease in the plasma albumin level. The yield of covalent binding of FP to plasma protein in AA rats was less than that in controls, being consistent with the decrease in the plasma acyl glucuronide level. Chirality 15:423–428, 2003. © 2003 Wiley‐Liss, Inc.
Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine‐induced seizures
Authors: Dinocourt Celine , Petanjek Zdravko , Freund Tamas F. , Ben‐Ari Yezekiel , Esclapez Monique
Published: April 2003

In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium‐binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA‐containing neurons in the stratum oriens of CA1 in pilocarpine‐treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O‐LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo‐axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin‐ and parvalbumin‐containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum‐moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine‐treated animals. These results indicate that the loss of somatostatin‐containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum‐moleculare (O‐LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin‐containing neurons corresponds to the death of axo‐axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model. J. Comp. Neurol. 459:407–425, 2003. © 2003 Wiley‐Liss, Inc.
Long‐term effects of decreased noradrenergic central nervous system innervation on pain behavior and opioid antinociception
Authors: Jasmin Luc , Boudah Abdennacer , Ohara Peter T.
Published: April 2003

Here we examine whether a permanent reduction in the noradrenergic (NA) innervation of the spinal cord leads to a chronic decreased nociceptive threshold. NA denervation of rats was achieved by intrathecal injection of dopamine beta‐hydroxylase antibodies conjugated to the toxin saporin. A subset of animals also underwent unilateral L5 spinal nerve ligature to induce sustained neuropathic pain behavior. NA fibers and terminals were lost throughout the spinal cord 2 weeks after toxin application and were still absent 12 months later, indicating that regeneration did not occur. There was also a widespread loss of NA terminals in the cerebral cortex, whereas innervation of the hypothalamus and amygdala were close to normal and NA innervation of the brainstem was moderately reduced. There was extensive loss of NA cells in the locus coeruleus and A5 and A7 cell groups. Dopaminergic and serotoninergic innervation was normal. Intracerebroventricular injection of the toxin resulted in additional NA reduction in the hypothalamus, amygdala, and A1 and A2 cell groups. Long‐term removal of NA afferents did not affect nociceptive thresholds. Neuropathic animals showed greater mechanical hyperalgesia in the affected hindpaw only during the first 60 days after toxin. Rats lacking NA spinal afferents were less responsive to the antinociceptive effects of morphine, especially in the neuropathic hindpaw, and did not display opioid‐dependent stress analgesia. Finally, in the spinal cord of toxin‐treated rats, immunoreactivity for substance P was decreased, whereas that of its receptor (NK1) was increased. These animals exhibited antinociception to a low dose of an NK1 receptor antagonist. Our results suggest that NA contributes only modestly to determining the nociceptive threshold and that its antinociceptive effects are closely linked to opioidergic and tachykinergic neurotransmission. J. Comp. Neurol. 460:38–55, 2003. © 2003 Wiley‐Liss, Inc.
Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure
Authors: Cano Georgina , Passerin Alicia M. , Schiltz Jennifer C. , Card J. Patrick , Morrison Shaun F. , Sved Alan F.
Published: April 2003

The thermogenic activity of interscapular brown adipose tissue (IBAT) in response to physiologic stimuli, such as cold exposure, is controlled by its sympathetic innervation. To determine which brain regions might be involved in the regulation of cold‐evoked increases in sympathetic outflow to IBAT, the present study compared central nervous system (CNS) areas activated by cold exposure with brain regions anatomically linked to the sympathetic innervation of IBAT. Immunocytochemical localization of Fos was examined in the brains of rats exposed to 4°C for 4 hours. In a separate group of rats, the neural circuit involved in IBAT control, including the location of sympathetic preganglionic neurons in the spinal cord, was characterized with pseudorabies virus, a retrograde transynaptic tracer. Central noradrenergic and serotonergic groups related to the sympathetic outflow to IBAT also were identified. Localization of viral antigens at different survival times (66–96 hours) revealed infection in circumscribed CNS populations, but only a subset of the regions comprising this circuitry showed cold‐evoked Fos expression. The raphe pallidus and the ventromedial parvicellular subdivision of the paraventricular hypothalamic nucleus (PVH), both infected at early survival times, were the main areas containing sympathetic premotor neurons activated by cold exposure. Major cold‐sensitive areas projecting to spinal interneurons or to regions containing sympathetic premotor neurons, which became infected at intermediate intervals, included lateral hypothalamic, perifornical, and retrochiasmatic areas, anterior and posterior PVH, ventrolateral periaqueductal gray, and Barrington's nucleus. Areas infected later, most likely related to reception of cold‐related signals, comprised the lateral preoptic area, parastrial nucleus, dorsomedial hypothalamic nucleus, lateral parabrachial nucleus, and nucleus of the solitary tract. These interconnected areas, identified by combining functional and retrograde anatomic approaches, likely constitute the central circuitry responsible for the increase in sympathetic outflow to IBAT during cold‐evoked thermogenesis. J. Comp. Neurol. 460:303–326, 2003. © 2003 Wiley‐Liss, Inc.
Olfactory bulb core is a rich source of neural progenitor and stem cells in adult rodent and human
Authors: Liu Zhiping , Martin Lee J.
Published: April 2003

The olfactory bulb (OB) core is an extension of the rostral migratory stream and thus is a potential source of neural progenitor and neural stem cells. We characterized in vivo and in vitro neuronal progenitor and neural stem cells in the adult OB core. In mouse and rat, bromodeoxyuridine (BrdU) labeling showed that the OB core accumulates newly replicated cells. Nestin, a neuroepithelial stem cell marker, was enriched in the OB core. BrdU‐positive cells were immunolabeled for nestin and TUC4, a marker for early postmitotic neurons. The distributions of cells labeled for BrdU, TUC4, and nestin were similarly concentrated in the OB core. Nestin‐ and TUC4‐positive cells were also found in the OB of young and aged humans. Isolated and cultured OB core cells from adult rat and mouse had the capacity to generate numerous neurospheres. Adult OB core neurospheres were cryopreserved and subsequently cultured. Single cell clonal analysis of neurospheres revealed the capacity for self‐renewal and multipotency. Cultured adult OB core cells differentiated into neurons, astrocytes, and oligodendrocytes. Some neurons expressed choline acetlytransferase, substance P, and glutamic acid decarboxylase. Basic fibroblast growth factor potentiated the self‐renewal of cells and β‐nerve growth factor stimulated differentiation. OB‐derived neural stem cells in coculture with skeletal muscle cells were induced to become neurons expressing choline acetyltransferase and substance P and formed neuromuscular synaptic junctions on myocytes displaying acetylcholinesterase‐positive motor end plates. Cocultured OB‐derived neural stem cells with myoblast cells also generated nonneural cell progeny. We conclude that the adult mammalian OB core is a reservoir of neural progenitor cells and pluripotent neural stem cells. J. Comp. Neurol. 459:368–391, 2003. © 2003 Wiley‐Liss, Inc.