bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the mother's reproductive state on the hormonal status of daughters in marmosets (Callithrix kuhlii)
Authors: Puffer Alyssa M. , Fite Jeffrey E. , French Jeffrey A. , Rukstalis Michael , Hopkins Elizabeth C. , Patera Kimberly J.
Published: September 2004

Behavioral and endocrine suppression of reproduction in subordinate females produces the high reproductive skew that characterizes callitrichid primate mating systems. Snowdon et al. [American Journal of Primatology 31:11–21, 1993] reported that the eldest daughters in tamarin families exhibit further endocrinological suppression immediately following the birth of siblings, and suggested that dominant females exert greater control over subordinate endocrinology during this energetically challenging phase of reproduction. We monitored the endocrine status of five Wied's black tufted‐ear marmoset daughters before and after their mother delivered infants by measuring concentrations of urinary estradiol (E2), pregnanediol glucuronide (PdG), testosterone (T), and cortisol (CORT). Samples were collected from marmoset daughters 4 weeks prior to and 9 weeks following three consecutive sibling‐litter births when the daughters were prepubertal (M=6.1 months of age), peripubertal (M=11.9 months), and postpubertal (M=17.6 months). The birth of infants was associated with reduced ovarian steroid excretion only in the prepubertal daughters. In contrast, ovarian steroid levels tended to increase in the postpubertal daughters. Urinary E2 and T levels in the postpubertal daughters were 73.8% and 37.6% higher, respectively, in the 3 weeks following the birth of infants, relative to prepartum levels. In addition, peak urinary PdG concentrations in peri‐ and postpubertal daughters were equivalent to luteal phase concentrations in nonpregnant, breeding adult females, and all of the peri‐ and postpubertal daughters showed clear ovulatory cycles. Cortisol excretion did not change in response to the reproductive status of the mother, nor did the concentrations change across age. Our data suggest that marmoset daughters of potential breeding age are not hormonally suppressed during the mother's peripartum period or her return to fertility. These findings provide an additional example of species diversity in the social regulation of reproduction in callitrichid primates. Am. J. Primatol. 64:29–37, 2004. © 2004 Wiley‐Liss, Inc.
Dental topography and molar wear in Alouatta palliata from Costa Rica
Authors: Dennis John C. , Ungar Peter S. , Teaford Mark F. , Glander Kenneth E.
Published: September 2004

Paleoprimatologists depend on relationships between form and function of teeth to reconstruct the diets of fossil species. Most of this work has been limited to studies of unworn teeth. A new approach, dental topographic analysis, allows the characterization and comparison of worn primate teeth. Variably worn museum specimens have been used to construct species‐specific wear sequences so that measurements can be compared by wear stage among taxa with known differences in diet. This assumes that individuals in a species tend to wear their molar teeth in similar ways, a supposition that has yet to be tested. Here we evaluate this assumption with a longitudinal study of changes in tooth form over time in primates. Fourteen individual mantled howling monkeys (Alouatta palliata) were captured and then recaptured after 2, 4, and 7 years when possible at Hacienda La Pacifica in Costa Rica between 1989–1999. Dental impressions were taken each time, and molar casts were produced and analyzed using dental topographic analysis. Results showed consistent decreases in crown slope and occlusal relief. In contrast, crown angularity, a measure of surface jaggedness, remained fairly constant except with extreme wear. There were no evident differences between specimens collected in different microhabitats. These results suggest that different individual mantled howling monkeys wear their teeth down in similar ways, evidently following a species‐specific wear sequence. Dental topographic analysis may therefore be used to compare morphology among similarly worn individuals from different species. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
Relationship between ovarian cycle phase and sexual behavior in female Japanese macaques (Macaca fuscata)
Authors: O'Neill Ann C. , Fedigan Linda M. , Ziegler Toni E.
Published: September 2004

We conducted behavioral observations simultaneously with fecal sample collection on eight nonlactating females 2–3 times per week, October 1997–March 1998, to examine the relationship between ovarian hormones and the sexual behavior of female Japanese macaques (Macaca fuscata) during the mating season. We analyzed samples by enzyme immunoassay for fecal hormone levels. Hormone profiles of estrone‐glucuronide (E1) and pregnanediol‐glucuronide (PdG) were used to separate ovarian cycles into three phases (follicular, periovulatory, and luteal). Hormonal profiles indicate average cycle lengths of 27.6 ± 4.2 days (± SD; n = 26). Average lengths of the luteal and follicular phases were 12.3 ± 3.8 days (± SD) and 8.3 ± 3.4 days (± SD), respectively. We observed female Japanese macaques engaging in sexual activity throughout the ovarian cycle, with the highest rates occurring during the follicular and periovulatory phases as compared to the luteal phase. The attractivity of female Japanese macaques increased significantly during the follicular and periovulatory phases of the ovarian cycle, when E1 levels are peaking and PdG levels drop to baseline. In addition, females displayed a significant increase in proceptive behavior during the follicular and periovulatory phases. Grooming bouts, as well as proximity between female and male macaques, also increased significantly during the follicular and periovulatory phases. We conclude that fluctuating levels of ovarian hormones in different phases of the cycle are significantly associated with variable rates of copulatory and pericopulatory behaviors in these Japanese macaque females. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
How international arbitration bridges global markets in transition economies
Authors: Katz Lucy V.
Published: September 2004

The five feature articles discuss current principles that are essential for business ADR practice regardless of where it is taking place. Lucy V. Katz of Fairfield, Conn., leads off at right with insights into how arbitration practice is helping open up markets in China, Cuba, North Korea, and Vietnam—not traditionally hospitable markets for Western companies, to put it mildly.
New English ADR principles advance law, raise new questions
Authors: Newmark Christopher C. , Dahlberg Andrea
Published: September 2004

The clash between United Kingdom courts' backing of mediation, and matters where parties refuse to participate, as described by Christopher C. Newmark and Andrea Dahlberg of London, provide a preview of issues all court programs eventually must address.
Dealing with ‘selective perception’ and bad‐faith allegations in commercial settlement discussions
Authors: McIlwrath Michael
Published: September 2004

Michael McIlwrath of Florence, Italy, describes an ADR training session that shows how international negotiating positions develop.
Parkinsonian signs and substantia nigra neuron density in decendents elders without PD
Authors: Ross G. Webster , Petrovitch Helen , Abbott Robert D. , Nelson James , Markesbery William , Davis Daron , Hardman John , Launer Lenore , Masaki Kamal , Tanner Caroline M. , White Lon R.
Published: September 2004

Substantia nigra (SN) neurons were counted on single, transverse caudal midbrain sections from 217 male participants in the Honolulu‐Asia Aging Study, aged 74–97 years at death. Quadrants areas within the SN were determined with a planimeter and neuronal density was expressed as neurons/mm2 for 10 Parkinson's disease (PD) cases, 29 incidental Lewy body cases, and 178 controls with neither condition. Mean densities in all quadrants were significantly lower in the PD group compared with the other groups (p = 0.006). This relationship was strongest in the ventrolateral quadrant. In a subgroup of 50 controls who were examined with the Unified Parkinson's Disease Rating Scale an average of 2.1 years prior to death, there was an association of stooped posture (p = 0.009), postural instability (p = 0.013), body bradykinesia (p = 0.048), and gait disturbance (p = 0.05) with neuron density in the dorsolateral quadrant; and impaired speech (p = 0.014), abnormal facial expression (p = 0.022), and difficulty rising from a chair (p = 0.032) with neuron density in the dorsomedial quadrant. There was a significant association of increasing number of signs present with decreasing neuron density in both quadrants (p = 0.001 for trend). Low SN neuron density may be the basis for parkinsonian signs in the elderly without PD. Ann Neurol 2004
Carbonic anhydrase–related protein VIII: Autoantigen in paraneoplastic cerebellar degeneration
Authors: Bataller Luis , Sabater Lidia , Saiz Albert , Serra Carles , Claramonte Berta , Graus Francesc
Published: September 2004

Serum of a patient with paraneoplastic cerebellar degeneration (PCD) and malignant melanoma had a unique reactivity with Purkinje cells that was not observed in serum of patients with PCD and other tumors, or with malignant melanoma without paraneoplastic syndromes. The screening of a human cerebellar complementary DNA expression library with the patient's serum resulted in the isolation of the CA8 gene. CA8 encodes carbonic anhydrase–related protein (CARP) VIII, preferentially expressed in Purkinje cells. The patient had intrathecal synthesis of CARP VIII antibodies. One of seven melanomas tested expressed CARP VIII. These data suggest CARP VIII may be an autoantigen involved in the pathogenesis of melanoma‐associated PCD. Ann Neurol 2004
Methoden zur chemischen Synthese von Fullerenen
Authors: Scott Lawrence T.
Published: September 2004

Das bekannteste Fulleren, C60 , wurde mit chemischen Methoden synthetisiert. Über zehn Jahre lang wurden im Labor des Autors bei der Synthese und dem Studium von offenen geodätischen Polyarenen Erfahrungen gesammelt, auf deren Grundlage die Strategie und Methodik für die Herstellung einer Vorstufe aus 60 Kohlenstoffatomen und deren Schließung zum Fulleren ausgearbeitet wurden. In diesem Aufsatz beschreibt der Autor aus seiner persönlichen Perspektive, wie die neuen Synthesemethoden entwickelt und eingesetzt wurden.
Titelbild: Ein zweikerniges, dreisträngiges Helicat mit einem Diamid‐verbrückten Brenzcatechin/ Benzoldithiol‐Liganden (Angew. Chem. 36/2004)
Authors: Hahn F. Ekkehardt , Schulze Isfort Christian , Pape Tania
Published: September 2004

Helices sind ein universelles Bauprinzip: Sie werden im atomaren Bereich genauso beobachtet wie bei interstellaren Spiralnebeln. Das auf dem Titelbild gezeigte zweikernige, dreisträngige Helicat enthält einen neuartigen Liganden mit Brenzcatechinato‐ und o‐Benzoldithiolato‐Donorgruppen. Es wird nur das Regioisomer mit paralleler Ligandenanordnung bestehend aus einem Enantiomerenpaar beobachtet. Mehr dazu erfahren Sie in der Zuschrift von F. E. Hahn et al. auf S. 4911 ff.
Preparation of an ultraviolet‐curable water‐borne poly(urethane acrylate)/silica dispersion and properties of its hybrid film
Authors: Yu Hao , Yuan Qiaolong , Wang Dening , Zhao Yinghong
Published: September 2004

An organic–inorganic hybrid material was prepared through the addition of nanometer fumed silica partly modified by dimethyl dichlorosilane into a water‐borne poly(urethane acrylate) (PUA) anionomer. A PUA/silica hybrid film was made via ultraviolet curing. The mechanical properties of the hybrid film were studied. The tensile strength, elongation at break, pendulum hardness and the glass‐transition temperature of the hybrid material increased with increasing content of silica. Scanning electron microscopy showed an asymmetrical distribution of modified silica in PUA. Atomic force microscopy demonstrated that silica particles could make the surface of the film smooth. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1347–1352, 2004
Degradation of polyimide film under vacuum ultraviolet irradiation
Authors: Peng Guirong , Hao Wenguang , Yang Dezhuang , He Shiyu
Published: September 2004

The degradation of PI film irradiated with VUV in a wavelength of 5 to 200 nm is investigated. The results show that transparency of PI film decreases obviously after irradiation and more obviously for the film irradiated with VUV of higher intensity. In addition, the absorption line red‐shifts for the PI film. The XPS and FTIR analyses results indicate that decarbonylation and the condensation of the benzene group take place under the irradiation and that carbonification takes place under 100 VUV suns. The change of optical property could be attributed to the stabilizing of the conjugation group and as well as to the carbonification to some extent. The character of VUV on polymer degradation is discussed. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1370–1374, 2004
Influence of the preparation conditions on the morphology of polyaniline electrodeposited by the pulse galvanostatic method
Authors: Jiao S. Q. , Zhou H. H. , Chen J. H , Luo S. L , Kuang Y. F.
Published: September 2004

The pulse galvanostatic method (PGM) and galvanostatic method (GM) were used to electrodeposit polyaniline (PANI) in H2SO4 solutions. Scanning electron microscopy studies showed that PANI prepared with GM had a granular morphology similar to other researchers' results, whereas nanofibular PANI was prepared with PGM. Furthermore, the relationship between the synthetic conditions and morphology of PANI electrodeposited by PGM was investigated. Under some preparation conditions (i.e., mean current density of PGM = 1–4 mA cm−2, ratio of the on‐pulse period to the off‐pulse period = 0.25–10, temperature = 10–30°C, and experimental frequency = 10–1000 Hz), nanofibular PANI was obtained, whereas flake PANI or granular PANI was prepared under other conditions. Nanosize PANI could result from the highly polarized current of the pulse current signal. The appropriate pulse peak current during the on‐pulse period not only produced high electrochemical polarization but also did not lead to overoxidation of PANI; meanwhile, the monomer at the electrode/solution interface could be sufficiently supplied during the off‐pulse period. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94:1389–1394, 2004
Synthesis, characterization, and flocculation characteristics of hydrolyzed and unhydrolyzed polyacrylamide grafted xanthan gum
Authors: Adhikary P. , Singh R. P.
Published: September 2004

The partial hydrolysis of xanthan gum‐g‐polyacrylamide was carried out in alkaline medium. Four grades of partially hydrolyzed products were synthesized by varying the reaction parameters. The neutralization equivalents of these products were determined by titration with standard sodium hydroxide solution. The flocculation characteristics of all the hydrolyzed graft copolymers and the unhydrolyzed xanthan gum‐g‐polyacrylamide were determined in 5 wt % iron ore and kaolin suspensions. The partially hydrolyzed product with neutralization equivalent of 1000 g showed better performance than that of other partially hydrolyzed products, but all hydrolyzed products exhibited poorer performance than that of the unhydrolyzed product in flocculation. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1411–1419, 2004
Water stability of high‐molecular‐weight (HMW) syndiotacticity‐rich poly(vinyl alcohol) (PVA)/HMW atactic PVA/iodine complex blend films
Authors: Yeum Jeong Hyun , Kwak Jin Woo , Han Sung Soo , Kim Sam Soo , Ji Byung Chul , Noh Seok Kyun , Lyoo Won Seok
Published: September 2004

To precisely identify the effect of blend ratios of syndiotacticity‐rich poly(vinyl alcohol) (s‐PVA)/atactic PVA (a‐PVA) on the water stability of s‐PVA/a‐PVA/iodine complex blend films, we prepared two PVAs with similar number‐averaged degrees of polymerization of 4000 and degrees of saponification of 99.9% and with different syndiotactic diad contents of 58.5 and 53.5%, respectively. The desorption behavior of iodine in s‐PVA/a‐PVA/iodine complex films in water was investigated in terms of the solubility of s‐PVA/a‐PVA blend films in water. The degree of solubility of s‐PVA/a‐PVA blend films with s‐PVA content over 50% in water at 70°C was limited to about 10–20%, whereas that of s‐PVA/a‐PVA blend films with s‐PVA content of 10% was 85% under the same conditions. The degree of iodine desorption of complex blend films decreased with increasing s‐PVA content. The degree of iodine desorption of s‐PVA/a‐PVA drawn film with s‐PVA content of 90% was limited to 7%, regardless of the soaking temperature from 30 to 70°C. The desorption of iodine in water was strongly affected by the dissolution of blends. Moreover, the stability of iodine in the drawn s‐PVA/a‐PVA/iodine blend films in hot water was far superior to that of the undrawn film. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1435–1439, 2004
Syndiospecific styrene polymerization with CpTiCl3/MAO: Effects of the order of reactant addition on polymerization and polymer properties
Authors: Huang Bill , Cao Kun , Li Bo‐Geng , Zhu Shiping
Published: September 2004

Syndiospecific styrene (St) polymerization, catalyzed by the CpTiCl3/methylaluminoxane (MAO) system, was investigated using two different activation procedures. The polymerization parameters included polymerization time, temperature (∼25–100°C), ratio of [Al]/[Ti] (∼100–1000), and catalyst precursor concentration (∼0.5–10.0 × 10−4 mol Ti/L). It was found that adding reactants in the order of (CpTiCl3 + MAO) + St (Injection of Styrene mode) gave much higher monomer conversion rates, higher weight‐average molecular weights, and narrower molecular weight distributions than for the (St + MAO) + CpTiCl3 (Injection of Catalyst mode). The former also yielded significantly higher syndiotacticity fractions. Differential scanning calorimetry measurements showed multiple peaks exhibiting polymorphism in crystalline syndiotactic polystyrene samples. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1449–1455, 2004
Swelling behavior and pervaporation properties of new composite membrane systems: Porous polyethylene film‐poly(acrylic acid) hydrogel
Authors: Buyanov A. L. , Revel'Skaya L. G. , Rosova E. Yu. , Elyashevich G. K.
Published: September 2004

A new type of composite membrane for pervaporation has been developed. These membranes were prepared by free‐radical copolymerization of acrylic acid with a macromolecular polyfunctional crosslinker (allylhydroxyethylcellulose) inside the porous polyethylene (PE) film. It was shown that the porous structure of the PE matrix is filled with poly(acrylic acid) (PAA), and a layer of acid is formed on the film surface. To investigate the effect of the porous matrix on the composite membrane properties, a hydrogel membrane of crosslinked PAA was also prepared without the matrix using the same procedure. PAA in both membranes was in the neutralized form (K+). Swelling behavior of the membranes and their separation characteristics for pervaporation were investigated in water–ethanol solutions depending on the ethanol concentration. All membranes exhibited a high degree of equilibrium swelling (Q = 20–50 g/g) in dilute ethanol solutions (0–30 vol %), and Q sharply dropped to 1.5–2 g/g at a EtOH concentration of 30–40 vol % due to collapse of the gel. All membranes under study were highly permeable and selective to water over a wide range of ethanol concentrations in the feed (50–96 vol %), but composite membranes had a higher separation factor due to the restriction effect of the matrix porous structure on swelling of PAA(K+) inside the pores. However, composite membranes were characterized by a lower permeation rate, compared to the crosslinked PAA membranes without a matrix, because of their lower effective surface for diffusion. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1461–1465, 2004
The use of polymers in the treatment of produced oily waters
Authors: Feder Angelo L. , González Gaspar , Teixeira Carmen L. S. , Lucas Elizabete F.
Published: September 2004

In this work, a new flocculant agent was developed based on a non‐ionic and water‐soluble polymer, poly(vinyl alcohol) (PVA), in order to treat oily waters from peteroleum production. Changes on its HLB were made to generate hydrophobic zones that work like flocculant agents, based on “hydrophobic bridges mechanism.” Incorporation of 12 to 18 carbon atoms and carbamate groups in several concentrations were carried out. Little insertions of hydrophobic groups reduce the brine solubility, due to the inter‐ and intramolecular interactions; however, certain content of carbamate groups increases the resistance in a brine environment. The influence of molecular weight and the hydrolysis grade of PVA were verified as the flocculation efficiency. Their performance was verified in synthetic oily emulsion by flocculation tests. The flakes generated are different from those generated when using commercial products. High amount of additive decreases the flocculation efficiency. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1473–1479, 2004
The flocculation and rheological characteristics of hydrolyzed and unhydrolyzed grafted sodium alginate in aqueous solutions
Authors: Biswal D. R. , Singh R. P.
Published: September 2004

Sodium alginate is a natural anionic polysaccharide obtained from natural and microbial resources. It is also used as a flocculating agent and thickener. It is grafted with polyacrylamide, in the presence of ceric ammonium nitrate (CAN) as an initiator. The graft copolymer (SAG‐g‐PAM) is again hydrolyzed with some amount of alkali. The flocculation characteristics of hydrolyzed graft copolymer (Hyd SAG‐g‐PAM) are compared with that of the unhydrolyzed ones, in 5 wt % kaolin and 10 wt % iron ore suspensions. The flocculation characteristics of the hydrolyzed graft copolymer are also compared with those of some of the commercial flocculants. The SAG‐g‐PAM and Hyd SAG‐g‐PAM are characterized by IR and intrinsic viscosity measurements. The rheological properties of aqueous solutions of hydrolyzed and unhydrolyzed graft copolymers are measured by Advanced AR‐1000 Rheometer. There is drastic enhancement in flocculation and viscosifying characteristics on hydrolysis of the graft copolymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1480–1488, 2004
Mechanical properties and morphological structures relationship of blends based on sulfated EPDM ionomer and polypropylene
Authors: Su Zhanpai , Jiang Pingkai , Li Qiang , Wei Ping , Wang Genlin , Zhang Yong
Published: September 2004

The mechanical properties and morphological structures of blends based on Zn2+ neutralized low degree sulfated ethylene propylene diene monomer rubber (Zn–SEPDM) ionomer and polypropylene (PP) were studied. It was found that Zn2+ neutralized low degree sulfated EPDM ionomer and PP blends, which are new thermoplastic elastomeric materials, have better mechanical properties than those of PP/EPDM blend. Theoretical analysis of tensile data suggests that there is an increase of the extent of interaction between PP and EPDM in the presence of a low degree of Zn2+, which is also an indicator of better interfacial adhesion between PP and Zn–SEPDM than that between PP and EPDM. SEM results proved that the finer dispersed phase sizes and the shorter interparticle distances are the main reasons for the improved mechanical properties of the PP/EPDM blend. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1504–1510, 2004
Graft copolymerization of methacrylamide onto acrylic fibers initiated by benzoyl peroxide
Authors: Çelik Meltem
Published: September 2004

Acrylic fibers were graft copolymerized with methacrylamide in aqueous media, using benzoyl peroxide as a free‐radical initiator. The grafting reactions were carried out within the 75–95°C temperature range, and the effect of initiator, monomer concentrations, and the amount of fiber on the graft yield were also investigated. The maximum graft yield was reached at the benzoyl peroxide concentration of 3.0 × 10−3 mol/L and the optimum temperature of 85°C. The activation energy of the reaction was found to be 33.8 kcal/mol at the temperature interval of 80–95°C. The grafted fibers were characterized with infrared spectroscopy, scanning electron microscopy, and thermogravimetry. The thermogravimetric analysis results revealed that the degradation temperature of the acrylic fibers increased with grafting. The scanning electron photographs showed that the homogeneous appearance of the fiber surface changed and a shell‐like heterogeneous structure occurred at the surface with an increasing degree of grafting. The moisture content and water absorption of grafted acrylic fibers was highly enhanced by grafting. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1519–1525, 2004
Sympathetic nervous system regulation of liver repair
Authors: Oben Jude A. , Diehl Anna Mae
Published: September 2004

This chapter reviews recent evidence that the sympathetic nervous system (SNS) regulates liver repair by modulating the phenotypes of hepatic stellate cells (HSCs), the liver's principal fibrogenic cells, and hepatic epithelial progenitors, i.e., oval cells. SNS nerve fibers touch HSCs and these cells express adrenoceptors, suggesting that HSCs may be targets for SNS neurotransmitters. HSCs also contain catecholamine biosynthetic enzymes, release norepinephrine (NE), and are growth‐inhibited by adrenoceptor antagonists. In addition, HSCs from mice with reduced levels of NE grow poorly in culture and exhibit inhibited activation during liver injury. Finally, growth and injury‐related fibrogenic responses are rescued by adrenoceptor agonists. Thus, certain SNS inhibitors (SNSIs) protect experimental animals from cirrhosis. Conversely, SNSIs enhance the hepatic accumulation of oval cells (OCs) in injured livers. This response is associated with improved liver injury. Because SNSIs do not affect the expression of cytokines, growth factors, or growth factor receptors that are known to regulate OCs, and OCs express adrenoceptors, it is conceivable that catecholamines influence OCs by direct interaction with OC adrenoceptors. Given evidence that the SNS regulates the viability and activation of HSCs and OCs differentially, SNSIs may be novel therapies to improve the repair of damaged livers. © 2004 Wiley‐Liss, Inc.
Hyperkeratosis in cystathionine beta synthase‐deficient mice: An animal model of hyperhomocysteinemia
Authors: Robert Karine , Maurin Nicole , Ledru Aurélie , Delabar Jean , Janel Nathalie
Published: September 2004

Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations. Patients with severe hyperhomocysteinemia have fine hair and thin skin, but it is unclear whether these changes are related to CBS deficiency or are coincidental. To investigate these aspects of hyperhomocysteinemia, we characterized skin abnormalities of CBS‐deficient mice, a murine model of severe hyperhomocysteinemia. Histological and histomorphometric analyses revealed that CBS‐deficient mice have wrinkled skin with hyperkeratinosis of the epidermis and thinning of the dermis. © 2004 Wiley‐Liss, Inc.
Modeling of the D2 Dopamine Receptor Arylpiperazine Binding Site for 1‐{2‐[5‐(1H‐benzimidazole‐2‐thione)]ethyl}‐4‐arylpiperazines
Authors: Šukalović Vladimir , Zlatović Mario , Andrić Deana , Roglić Goran , Kostić‐Rajacčić Sladjana , Šoškić Vukić
Published: September 2004

Docking of several 1‐{2‐[5‐(1H‐benzimidazole‐2‐thione)]ethyl}‐4‐ and 1‐benzyl‐arylpiperazines to the D2 dopamine receptor (DAR) was examined. The binding pocket of the D2 DAR defined according to Teeter and DuRand [1] was extended using the Insight II software. It was found that (i) the interaction of the protonated N1 of the piperazine ring with Asp86, (ii) the hydrogen bond formation between the benzimidazole part of the ligand and Ser141, as well as Ser122, and (iii) the edge‐to‐face interactions of the aromatic ring or arylpiperazine part of the ligand with Phe178, Tyr216 and Trp182 of the receptor represent the mayor stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could form one more hydrogen bond with Trp182. Bulky substituents in position 4 are not tolerated, due to the unfavorable sterical interaction with Phe178. Substituents in positions 2 and 3 are sterically well tolerated. Electron‐attractive groups (F, Cl, CF3, and NO2) decreased, while electron donors (‐OMe) and the second aromatic ring (naphthyl) increased the binding affinity, as compared to that of the parent compound 1. This can be explained by strong edge‐to‐face interactions of negative electrostatic surface potential (ESP) in the center of aromatic residues of the ligand with positive‐ESP protons in the aromatic residues of the receptor. Thus, besides the salt bridges and hydrogen bonds, edge‐to‐face interactions significantly contribute to arylpiperazine ligands forming complexes with the D2 DAR.
A genome‐wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage
Authors: Thompson Susan D. , Moroldo Marta B. , Guyer Laura , Ryan Mary , Tombragel Esther M. , Shear Edith S. , Prahalad Sampath , Sudman Marc , Keddache Mehdi A. , Brown W. Mark , Giannini Edward H. , Langefeld Carl D. , Rich Stephen S. , Nichols William C. , Glass David N.
Published: September 2004

Objective

Juvenile rheumatoid arthritis (JRA) represents a heterogeneous group of disorders with a complex genetic component. A genome scan was performed to detect linkage to JRA in 121 families containing 247 affected children in North America (the JRA Affected Sibpair [ASP] Registry).

Methods

Genotype data collected for HLA–DR and 386 microsatellite markers were subjected to multipoint nonparametric linkage analysis. Following analysis of the entire set of families, additional analyses were performed after a priori stratification by disease onset type, age at onset, disease course, and selected HLA–DRB1 alleles.

Results

Linkage of JRA to the HLA region was confirmed (logarithm of odds [LOD] score 2.26). Additional evidence supporting linkage of JRA was observed at 1p36 (D1S214; LOD 1.65), 19p13 (D19S216; LOD 1.72), and 20q13 (D20S100; LOD 1.75). For early‐onset polyarticular disease, evidence of linkage was found at chromosome 7q11 (D7S502; LOD 3.47). For pauciarticular disease, evidence supporting linkage was observed on chromosome 19p13 (D19S216; LOD 2.98), the same marker that supported linkage to the “JRA” phenotype. Other regions supporting linkage with JRA disease subtype included 20q13, 4q24, 12q24, and Xp11. Stratification of families based on the presence of the HLA–DR8 allele in affected siblings resulted in significant linkage observed at 2p25 (D2S162/D2S305; LOD 6.0).

Conclusion

These data support the hypothesis that multiple genes, including at least 1 in the HLA region, influence susceptibility to JRA. These findings for JRA are consistent with findings for other autoimmune diseases and support the notion that common genetic regions contribute to an autoimmune phenotype.
Down‐regulation of FLIP sensitizes rheumatoid synovial fibroblasts to Fas‐mediated apoptosis
Authors: Palao Guillermo , Santiago Begoña , Galindo María , Payá Mónica , Ramirez Juan C. , Pablos José L.
Published: September 2004

Objective

Hyperplasia of fibroblast‐like synoviocytes (FLS) contributes to chronic inflammation and joint destruction in rheumatoid arthritis (RA). FLICE‐inhibitory protein (FLIP) is an antiapoptotic protein that might prevent apoptotic elimination of FLS in response to death ligands such as tumor necrosis factor α (TNFα) or Fas ligand, which are present in RA synovium. Previous studies on FLIP expression by osteoarthritis (OA) and RA FLS have shown variable results, and the specific role of FLIP as an apoptosis inhibitor in these cells remains unclear. We undertook this study to investigate the expression and antiapoptotic function of FLIP in FLS.

Methods

We studied the expression of FLIP by immunohistochemistry and immunoblotting in synovial tissues or cultured FLS from RA and OA patients. FLS apoptosis was induced by an agonistic anti‐Fas monoclonal antibody and FLS were then quantified. We studied the effects of cycloheximide (CHX), TNFα, and FLIP antisense oligonucleotide on FLIP expression and FLS apoptotic susceptibility.

Results

FLIPL was the isoform mainly expressed in lining synoviocytes and cultured FLS. Synovial tissues and cultured FLS from OA and RA tissues displayed similar patterns and levels of expression of FLIP. Fas‐induced apoptosis was variable in different FLS lines, but differences between OA and RA groups were not detected. TNFα induced increases in FLIPL and FLIPS expression and protected RA FLS from apoptosis, while CHX induced the opposite effects. Down‐regulation of FLIP by antisense oligonucleotide strongly sensitized RA FLS to Fas‐mediated apoptosis.

Conclusion

Apoptosis susceptibility and FLIP expression are similar in OA and RA FLS. Down‐regulation of FLIP sensitizes RA FLS to Fas‐mediated apoptosis and may be a valuable tool for targeting RA FLS hyperplasia.
Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription
Authors: Wang B. , Ma L. , Tao X. , Lipsky P. E.
Published: September 2004

Objective

The ethyl acetate (EA) extract of Tripterygium wilfordii Hook F (TWHF) and its major active component, triptolide, have been reported to be effective in the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases. Nitric oxide (NO) has been recognized as an important mediator of inflammation. This study was therefore undertaken to examine the effects of the EA extract and triptolide on the production of NO and inducible NO synthase (iNOS) gene expression and transcription in vivo and in vitro.

Methods

Peritoneal macrophages from C57BL/6J mice treated orally with the EA extract of TWHF were assayed for NO production and iNOS messenger RNA (mRNA) expression by reverse transcriptase–polymerase chain reaction. The murine fibroblast cell line NIH3T3 was also assessed for NO production and iNOS mRNA expression, as well as for iNOS promoter activation, Oct‐1 nuclear binding capacity, and Oct‐1 protein content by transient transfection, electrophoretic mobility shift assay, and immunoblotting, respectively.

Results

NO production and iNOS mRNA expression by macrophages from C57BL/6J mice immunized with trinitrophenyl–bovine serum albumin in Freund's complete adjuvant were significantly inhibited by oral administration of the EA extract (52.3% and 59.8% of control, respectively, at one‐eighth of the dose that is lethal for 50% of the animals [LD50] and 21.0% and 38.1% of control, respectively, at one‐fourth the LD50). Moreover, the EA extract and triptolide significantly inhibited NO production in vitro in activated peritoneal macrophages, which reflected a decreased level of iNOS mRNA. Finally, triptolide inhibited promoter activity of the iNOS gene and induction of the activity of the regulator of iNOS transcription, Oct‐1.

Conclusion

The EA extract of TWHF and triptolide inhibit transcription of the iNOS gene. This may contribute to the antiinflammatory effects of this traditional herbal remedy.
Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis
Authors: Dervieux Thierry , Furst Daniel , Lein Diana Orentas , Capps Robert , Smith Katie , Walsh Michael , Kremer Joel
Published: September 2004

Objective

Methotrexate (MTX) enters cells through the reduced folate carrier (RFC‐1) and exerts part of its effects through polyglutamation to MTX polyglutamates (MTXPGs) and inhibition of 5‐aminoimidazole‐4‐carboxamide ribonucleotide transformylase (ATIC) and thymidylate synthase (TS). We investigated the contribution of common genetic polymorphisms in RFC‐1 (G80A), ATIC (C347G), and TS (28‐bp tandem repeats located in the TS enhancer region [TSER*2/*3]) and of MTXPGs to the effect of MTX in patients with rheumatoid arthritis.

Methods

The study was cross‐sectional. All patients received MTX for at least 3 months. The numbers of tender and swollen joints, the Visual Analog Scale (VAS) scores for the physician's global assessment of disease activity, and the modified Health Assessment Questionnaire scores were collected. Using the VAS score for the physician's assessment of patient's response to MTX, the population of patients was dichotomized into responders to MTX (VAS score ≤2 cm) and nonresponders to MTX (VAS score >2 cm). A pharmacogenetic index was calculated as the sum of homozygous variant genotypes (RFC‐1 AA + ATIC 347GG + TSER *2/*2) carried by the patients. MTXPG concentrations were measured in red blood cells (RBCs) by high‐performance liquid chromatography.

Results

The dose of MTX was not associated with the effects of MTX (P > 0.05). In contrast, increased RBC long‐chain MTXPG concentrations (median 40 nmoles/liter; range <5–131 nmoles/liter) and an increased pharmacogenetic index were associated with a lower number of tender and swollen joints (P < 0.05) and a lower score for the physician's global assessment of disease activity (P ≤ 0.001). Patients with RBC MTXPG levels of >60 nmoles/liter and carriers of a homozygous variant genotype were 14.0‐fold (95% confidence interval [95% CI] 3.6–53.8) and 3.7‐fold (95% CI 1.7–9.1), respectively, more likely to have a good response to MTX (P ≤ 0.01).

Conclusion

These data suggest that measuring RBC MTXPG levels and/or the common polymorphisms in the folate–purine–pyrimidine pathway may help in monitoring MTX therapy.
The influence of genetic variation in the HLA–DRB1 and LTA–TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept
Authors: Criswell Lindsey A. , Lum Raymond F. , Turner Kevin N. , Woehl Blanche , Zhu Yuanqing , Wang Jinyi , Tiwari Hemant K. , Edberg Jeffrey C. , Kimberly Robert P. , Moreland Larry W. , Seldin Michael F. , Bridges S. Louis
Published: September 2004

Objective

To examine the roles of specific genetic polymorphisms as predictors of response to treatment of early rheumatoid arthritis (RA).

Methods

Subjects included 457 patients with early RA (duration of ≤3 years) who participated in a randomized controlled trial comparing weekly methotrexate and 2 dosages of etanercept (10 mg twice weekly and 25 mg twice weekly). Our primary outcome measure was achievement of 50% improvement in disease activity according to the criteria of the American College of Rheumatology (ACR50 response) after 12 months of treatment. Subjects were genotyped for HLA–DRB1 alleles and polymorphisms in the following genes: TNF, LTA, TNFRSF1A, TNFRSF1B, FCGR2A, FCGR3A, and FCGR3B. Univariate and multivariate analyses were performed to define the impact of specific polymorphisms and haplotypes on response to treatment. Covariates for the multivariate analyses included sex, ethnicity, age, disease duration, and baseline values for rheumatoid factor and the tender and swollen joint counts.

Results

The presence of 2 HLA–DRB1 alleles encoding the shared epitope (SE) (compared with 1 or 0 copies) was associated with response to treatment with standard‐dose etanercept (odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.8–10.3). Among Caucasian patients, 2 extended haplotypes that included the HLA–DRB1 alleles *0404 and *0101 (both of which encode the SE) and 6 single‐nucleotide polymorphisms in the LTA–TNF region were associated with response to treatment. In a multivariate model that included treatment received and the aforementioned covariates, the ORs for the association of these haplotypes with achievement of an ACR50 response at 12 months were 2.5 (95% CI 0.8–7.3) and 4.9 (95% CI 1.5–16.1) for the *0404‐ and *0101‐containing haplotypes, respectively.

Conclusion

Genetic variation in the HLA–DRB1 and the LTA–TNF regions is significantly associated with response to treatment of early RA. These findings may have clinical application through the identification of patients who are most likely to benefit from treatment with methotrexate or etanercept.
Expression of chemokine and fibrosing factor messenger RNA in the urinary sediment of patients with lupus nephritis
Authors: Chan Rebecca Wing‐Yan , Lai Fernand Mac‐Moune , Li Edmund Kwok‐Ming , Tam Lai‐Shan , Wong Teresa Yuk‐Hwa , Szeto Carol Yi‐Ki , Li Philip Kam‐Tao , Szeto Cheuk‐Chun
Published: September 2004

Objective

Lupus nephritis is characterized by intrarenal inflammation. To assess the extent and severity of disease activity and renal involvement, this study examined the expression of transforming growth factor β (TGFβ) and monocyte chemoattractant protein 1 (MCP‐1) in the urinary sediment of patients with systemic lupus erythematosus (SLE).

Methods

We studied 106 patients with SLE who were classified according to their disease status as those with active disease, those with disease in remission, and those with nonrenal SLE. Ten healthy subjects were used as controls. Lupus activity was assessed by the SLE Disease Activity Index (SLEDAI). If renal biopsy was performed, the histologic activity index and chronicity index were determined, and a morphometry analysis of renal scarring was performed. The urinary expresssion of TGFβ and MCP‐1 messenger RNA (mRNA) was studied by real‐time quantitative polymerase chain reaction, and the corresponding protein concentrations of TGFβ and MCP‐1 in the urine were measured by enzyme‐linked immunosorbent assay (ELISA).

Results

Expression of TGFβ and MCP‐1 mRNA in the urinary sediment was significantly elevated in the active disease group (P < 0.001 for both). These expression levels of TGFβ and MCP‐1 mRNA correlated with the SLEDAI score (TGFβ r = 0.71, P < 0.001; MCP‐1 r = 0.72, P < 0.001), and also significantly correlated with the histologic activity index (TGFβ r = 0.487, P = 0.004; MCP‐1 r = 0.357, P = 0.038). The urinary protein concentration of MCP‐1, but not of TGFβ, correlated with the SLEDAI score (r = 0.66, P < 0.001). However, neither the protein concentration of TGFβ nor that of MCP‐1 as measured by ELISA in the urine correlated with the histologic activity index.

Conclusion

The measurement of urinary mRNA expression may be a noninvasive method for the assessment of lupus disease activity and the severity of renal involvement in patients with lupus nephritis.
Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of anti‐CD4 monoclonal antibody
Authors: Hayashi Yuki , Ishimaru Naozumi , Arakaki Rieko , Tsukumo Shin‐ichi , Fukui Hitomi , Kishihara Kenji , Shiota Hiroshi , Yasutomo Koji , Hayashi Yoshio
Published: September 2004

Objective

To determine whether eyedrop administration of an anti‐CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease.

Methods

The anti‐CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti–α‐fodrin antibody were examined.

Results

Eyedrop administration of anti‐CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti‐CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti‐CD4 mAb suppressed the local activation of CD4+ T cells rather than deleting CD4+ T cells, which reduced the expansion of pathologic CD4+ T cells against α‐fodrin.

Conclusion

These results demonstrate the remarkable efficacy of anti‐CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody‐based therapeutic strategy for patients with eye problems caused by SS as well as other diseases.
Age dependency of cartilage magnetic resonance imaging T2 relaxation times in asymptomatic women
Authors: Mosher Timothy J. , Liu Yi , Yang Qing X. , Yao Jing , Smith Ryan , Dardzinski Bernard J. , Smith Michael B.
Published: September 2004

Objective

Because the magnetic resonance imaging (MRI) transverse relaxation time (T2) of cartilage is sensitive to organization of collagen fibers in the cartilage, it may be a noninvasive image marker for senescent changes in cartilage collagen and early cartilage degeneration. The purpose of this study was to determine age‐dependent differences in cartilage T2 values in healthy asymptomatic women.

Methods

Quantitative T2 maps of patellar cartilage from 30 asymptomatic women ages 22–86 years were obtained using a 3.0T MRI scanner. The study population was stratified by age into 4 cohorts: 18–30, 31–45, 46–65, and 66–86 years. Spatial differences in cartilage T2 were determined as a function of normalized distance from bone. Older groups were compared with the 18–30‐year‐old group to determine the effects of age on cartilage T2 values. Regions were considered statistically significantly different if the mean T2 values between groups differed at P < 0.05.

Results

Mean cartilage T2 profiles were nearly identical for the 2 youngest cohorts. Compared with the 18–30‐year‐old group, T2 values were statistically significantly longer in the superficial 40% of cartilage in the 46–65‐year‐old group and over the entire cartilage thickness in the 66–86‐year‐old group.

Conclusion

The location of T2 elevations in women over the age of 45 years is consistent with the theory that senescent changes of cartilage collagen begin near the articular surface and progress to the deeper cartilage with advancing age.