bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipose tissue of human omentum is a major source of dendritic cells, which lose MHC Class II and stimulatory function in Crohn's disease
Authors: Bedford Penelope A , Todorovic Vesna , Westcott Edward D A , Windsor Alistair C J , English Nicholas R , Al-Hassi Hafid Omar , Raju Kankipati S , Mills Sarah , Knight Stella C
Published: July 2006

Adipose tissue is reported to contain monocyte-like pre-adipocytes, which may mature into macrophages, contributing to local inflammation. Dendritic cells (DC) can be derived from monocytes and initiate and regulate primary immune responses. We hypothesized, therefore, that adipose tissue may provide DC involved in local immune activity. To test this, we studied cells from human omental adipose tissue samples from 17 patients with benign gynecological disease. The hypothesis that adipose tissue DC are involved in inflammatory disease was tested by comparing these cells with those from 18 patients with Crohn's disease, where hypertrophy of adipose tissue suggests involvement in disease. A high proportion of the 1.33 ± 0.12 × 105 CD45-positive cells/mg, obtained from control omenta, expressed CD11c, CD1a, and CD83; costimulatory molecules CD40, CD80, and CD86; and major histocompatibility complex (MHC) Class II but little CD14, CD16, or CD33. Omental cells showing morphological characteristics of DC were also observed. Metrizamide gradient-enriched DC from these populations were potent stimulators of primary proliferation of allogeneic T cells in mixed leukocyte reactions. Increased numbers of CD45+ cells from omentum of Crohn's patients (4.50±1.08×105 CD45+ cells/mg) contained higher percentages of CD11c+ and CD40+ cells (80.8±3.8% vs. 63.4±6, P=0.032; 77.9±4% vs. 58.8±6.5, P=0.029, respectively), but MHC Class II and stimulatory capacity were almost completely lost (P=<0.001), suggesting innate activation but lost capacity to stimulate adaptive immune responses. Granulocytes were also present amongst the omental cells from Crohn's patients. Results indicated that omentum may provide DC, which could “police” local infections and contribute to and/or reflect local inflammatory activity.
The Suppressor of Cytokine Signaling 3 Inhibits Leptin Activation of AMP-Kinase in Cultured Skeletal Muscle of Obese Humans
Authors: Steinberg Gregory R. , McAinch Andrew J. , Chen Michael B. , O’Brien Paul E. , Dixon John B. , Cameron-Smith David , Kemp Bruce E.
Published: July 2006

Context: Leptin is thought to regulate whole-body adiposity and insulin sensitivity, at least in part, by stimulating fatty acid metabolism via activation of AMP-kinase (AMPK) in skeletal muscle. Human obesity is associated with leptin resistance, and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents.

Objective: The objective of the study was to investigate the effects of leptin on fatty acid oxidation and AMPK signaling in primary myotubes derived from lean and obese skeletal muscle and evaluate the contribution of SOCS3 to leptin resistance and AMPK signaling in obese humans.

Results: We demonstrate that leptin stimulates AMPK activity and increases AMPK Thr172 and acetyl-CoA carboxylase-β Ser222 phosphorylation and fatty acid oxidation in lean myotubes but that in obese subjects leptin-dependent AMPK signaling and fatty acid oxidation are suppressed. Reduced activation of AMPK was associated with elevated expression of IL-6 (∼3.5-fold) and SOCS3 mRNA (∼2.5-fold) in myotubes of obese subjects. Overexpression of SOCS3 via adenovirus-mediated infection in lean myotubes to a similar degree as observed in obese myotubes prevented leptin but not AICAR (5-amino-imidazole-4-carboxamide-1-β-d-ribofuranoside) activation of AMPK signaling.

Conclusions: These data demonstrate that SOCS3 inhibits leptin activation of AMPK. These data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.
Mechanism of Sulfur Inversion in Sulfide Complexes of Gold(I) and Gold(III)
Authors: Toyota Shinji , Oki Michinori
Published: July 2006

Kinetic parameters for the sulfur inversion in various gold chloride complexes of alkyl benzyl sulfides were measured by the dynamic NMR method in order to obtain conclusive evidence for the inversion mechanism. A feature of kinetic data is that entropies of activation are nearly zero both in the gold(III) and gold(I) complexes, this suggesting that the sulfur inversion takes place via pyramidal inversion mechanism without breakage of the Au–S coordination bonds but not the dissociative mechanism. The negligible solvent effect on the inversion rates in the gold(III) and gold(I) complexes supports this mechanism as well. The barrier to sulfur inversion is higher by 2.9 kcal mol−1 in the gold(III) complexes than in the corresponding gold(I) complexes. The formal gold(II) complex exists as 1 : 1 mixture of gold(I) and gold(III) complexes in solution, each of them showing the dynamic behavior independently. The effect of oxidation state of the central gold atom on the sulfur inversion is discussed on the basis of MO calculation.
Reactions of Sulfoxides with Magnesium Amides. Transformation of Sulfoxides into Sulfides, Dithioacetals, and Vinyl Sulfides
Authors: Kobayashi Kazuhiro , Kawakita Masataka , Yokota Kouichi , Mannami Tohru , Yamamoto Koji , Morikawa Osamu , Konishi Hisatoshi
Published: July 2006

The reactions of sulfoxides with magnesium amides generated in situ from the reaction of ethylmagnesium bromide and secondary amines, such as diisopropylamine (DIPA) or 2,2,6,6-tetramethylpiperidine (TMP) in diethyl ether, were examined. Diaryl sulfoxides were heated with the diisopropylaminomagnesium reagent in diethyl ether to give the corresponding diaryl sulfides in 42—52% yields. Sulfoxides bearing hydrogens at the α-positon only (RSOCH2R1) reacted with the tetramethylpiperidinomagnesium reagent at room temperature to produce the corresponding dithioacetals (RSCHR1SR) in 47—86% yields. The treatment of sulfoxides bearing hydrogens both at the α- and β-positions (RSOCHR1CHR2R3) with the magnesium amides at room temperature afforded the corresponding vinyl sulfides (RSCR1=CR2R3) in 52—72% yields accompanying 2.3—27% yields of the corresponding dithioacetals. The pathways leading to the products involving the formation of the sulfur-stabilized carbonium ion intermediates are discussed.
Expedient Synthesis of an Anomerically Modified Trisaccharide Component of the Capsular Polysaccharide from Streptococcus pneumoniae Type 19F
Authors: Kaji Eisuke , Matsui Eiko , Kobayashi Mie , Zen Shonosuke
Published: July 2006

A practical stereoselective synthesis is described for α-d-ManNAc-(1→4)-α-d-Glc-(1→2)-l-Rha, an anomerically modified trisaccharide component of the capsular polysaccharide of Streptococcus pneumoniae type 19F. The key intermediary disaccharide, 2-(benzoyloxyimino)-2-deoxyglycosyl-α(1→4)-glucoside, was prepared by α-selective glycosylation (AgOTf–TMU/CH2Cl2, 90%) of a suitably blocked p-methoxybenzyl 2,3,6-tri-O-benzyl-β-d-glucopyranoside with 3,4,6-tri-O-benzoyl-2-(benzoyloxyimino)-2-deoxy-α-d-arabino-hexopyranosyl bromide, and converted into an α-d-ManNAc-(1→4)-α-d-Glc-(1→MBn) derivative by means of a manno-selective reduction (BH3·THF → Ac2O, 55%). Consecutive anomeric activation (1-OMBn → 1-OH → 1-F, 45% over 2 steps), glycosylation (SnCl2–AgClO4/CH2Cl2, 71%, α : β = 2 : 1) of 2-OH of benzyl 3,4-di-O-benzyl-α-l-rhamnopyranoside, and deblocking (NaOMe → Pd-C/H2, 90%) gave the target trisaccharide.
Altered Balance of Glutamatergic/GABAergic Synaptic Input and Associated Changes in Dendrite Morphology after BDNF Expression in BDNF-Deficient Hippocampal Neurons
Authors: Singh B. , Henneberger C. , Betances D. , Arevalo M. A. , Rodríguez-Tébar A. , Meier J. C. , Grantyn R.
Published: July 2006

Cultured neurons frombdnf−/− mice display reduced densities of synaptic terminals, althoughin vivothese deficits are small or absent. Here we aimed at clarifying the local responses to postsynaptic brain-derived neurotrophic factor (BDNF). To this end, solitary enhanced green fluorescent protein (EGFP)-labeled hippocampal neurons frombdnf−/− mice were compared withbdnf−/− neurons after transfection with BDNF,bdnf−/− neurons after transient exposure to exogenous BDNF, andbdnf+/+ neurons in wild-type cultures. Synapse development was evaluated on the basis of presynaptic immunofluorescence and whole-cell patch-clamp recording of miniature postsynaptic currents. It was found that neurons expressing BDNF::EGFP for at least 16 h attracted a larger number of synaptic terminals than BDNF-deficient control neurons. Transfected BDNF formed clusters in the vicinity of glutamatergic terminals and produced a stronger upregulation of synaptic terminal numbers than high levels of ambient BDNF. Glutamatergic and GABAergic synapses reacted differently to postsynaptic BDNF: glutamatergic input increased, whereas GABAergic input decreased. BDNF::EGFP-expressing neurons also differed from BDNF-deficient neurons in their dendrite morphology: they exhibited weaker dendrite elongation and stronger dendrite initiation. The upregulation of glutamatergic synaptic input and the BDNF-induced downregulation of GABAergic synaptic terminal numbers by postsynaptic BDNF depended on tyrosine receptor kinase B activity, as deduced from the blocking effects of K252a. The suppression of dendrite elongation was also prevented by block of tyrosine receptor kinase B but required, in addition, glutamate receptor activity. Dendritic length decreased with the number of glutamatergic contacts. These results illuminate the role of BDNF as a retrograde synaptic regulator of synapse development and the dependence of dendrite elongation on glutamatergic input.
Depressive Symptoms as a Longitudinal Predictor of Sexual Risk Behaviors Among US Middle and High School Students
Authors: Lehrer Jocelyn A. , Shrier Lydia A. , Gortmaker Steven , Buka Stephen
Published: July 2006

OBJECTIVE. The purpose of this study was to examine whether depressive symptoms are predictive of subsequent sexual risk behavior in a national probability sample of US middle and high school students.

METHODS. Sexually active, unmarried, middle and high school students (n = 4152) participated in home interviews in waves I and II of the National Longitudinal Study of Adolescent Health, at an ∼1-year interval. Associations between baseline depressive symptoms and sexual risk behaviors over the course of the following year were examined separately for boys and girls, adjusting for demographic variables, religiosity, same-sex attraction/behavior, sexual intercourse before age 10, and baseline sexual risk behavior.

RESULTS. In adjusted models, boys and girls with high depressive symptom levels at baseline were significantly more likely than those with low symptom levels to report ≥1 of the examined sexual risk behaviors over the course of the 1-year follow-up period. For boys, high depressive symptom levels were specifically predictive of condom nonuse at last sex, birth control nonuse at last sex, and substance use at last sex; these results were similar to those of parallel analyses with a continuous depression measure. For girls, moderate depressive symptoms were associated with substance use at last sex, and no significant associations were found between high depressive symptom levels and individual sexual risk behaviors. Parallel analyses with the continuous depression measure found significant associations for condom nonuse at last sex, birth control nonuse at last sex, ≥3 sexual partners, and any sexual risk behavior.

CONCLUSION. In this study, depressive symptoms predicted sexual risk behavior in a national sample of male and female middle and high school students over a 1-year period.
A Randomized, Controlled Trial of the Effectiveness of an Early-Intervention Program in Reducing Parenting Stress After Preterm Birth
Authors: Kaaresen Per Ivar , Rønning John A. , Ulvund Stein Erik , Dahl Lauritz B.
Published: July 2006

BACKGROUND. Preterm birth has been associated with increased parenting stress in early infancy, and some reports have found this to be a risk factor for later behavioral problems. There are, however, few studies and conflicting results. Information about the fathers is scarce.

OBJECTIVES. Our goal was to study the effects of an early-intervention program on parenting stress after a preterm birth until 1 year corrected age.

METHODS. A randomized, controlled trial was conducted including infants with a birth weight <2000 g treated at the University Hospital of North Norway Trust, which serves the 2 northern-most counties in Norway, to examine the effects of a modified version of the Mother-Infant Transaction Program on parenting stress measured by the Parenting Stress Index. A term control group was also recruited. The Parenting Stress Index was administered to the mothers at 6 and 12 months’ corrected age and to the fathers at 12 months’ corrected age. The intervention consisted of 8 sessions shortly before discharge and 4 home visits by specially trained nurses focusing on the infant’s unique characteristics, temperament, and developmental potential and the interaction between the infant and the parents.

RESULTS. Seventy-one infants were included in the preterm intervention group, and 69 were included in the preterm control group. The preterm groups were well balanced. Seventy-four infants were included in the term control group. Compared with the preterm controls, both the mothers and fathers in the preterm intervention group reported significant lower scores in child domain, parent domain, and total stress on all occasions except the mother-reported child domain at 12 months. These differences were not related to birth weight or gestational age. The level of stress among the preterm intervention group was comparable to their term peers. Both parents in the intervention group reported consistently lower scores within the distractibility/hyperactivity, reinforces parents, competence, and attachment subscales compared with the preterm control group. There were no differences in mean summary stress scores between the mothers and fathers in the 2 preterm groups at 12 months, but the intraclass correlation coefficient was higher in the intervention group.

CONCLUSIONS. This early-intervention program reduces parenting stress among both mothers and fathers of preterm infants to a level comparable to their term peers. We are now studying whether this will result in long-term beneficial effects.
Development of a Child Safety Seat Hassles Scale in a Largely Low-Income Latino Population
Authors: Agran Phyllis F. , Anderson Craig , Winn Diane G.
Published: July 2006

OBJECTIVE. High rates of use of child safety seats have been achieved. A remaining challenge in child passenger safety is to reach the Healthy People 2010 objective of child safety seat use to 100%. Several factors have been reported to influence child safety seat use. A child safety seat Hassles Scale was developed to explore hassles that are associated with child safety seat nonuse.

METHODS. Focus groups with violators of the California Child Passenger Safety Law provided data to construct the 29-item Hassles Scale. The scale was used in an interview that was conducted with 132 parents who were cited for violation of the law and whose children were 12 to 47 months of age and weighed 20 to 40 pounds. Interviews were conducted 3 months after parents paid the fine for the citation. Each hassle was rated 0 to 3 on frequency and intensity. Parent report of child safety seat use was obtained. Factor analysis was used to construct subscales. Relationship of subscale frequency and intensity scores to reported child safety seat use was assessed with linear regression.

RESULTS. The sample was 86% Latino, 45% Spanish-speaking, and 55% with income <$30000. Thirty-one percent of the parents reported that the child did not now always use a child safety seat. Four subscales were identified: child, crowding/inconvenience, busy, and vehicle. Only the frequency of the child subscale items (eg, resists, gets out of seat) and the frequency and the intensity of the crowding/inconvenience subscale items (eg, child safety seat takes up too much room, too many passengers) were related to child safety seat nonuse. Sixty-nine percent agreement with parent report of child safety seat use was achieved using only the frequency scores for the 9 items in the 2 subscales child and crowding/inconvenience, compared with 65% for the 29-item scale.

CONCLUSIONS. In this low-income largely Latino population of violators, self-report of “always using a child safety seat” when transporting their child was low (59%). Child safety seat nonuse was related to hassles that are associated with child behaviors and vehicle crowding/inconvenience. The child safety seat Hassles Scale documented barriers and difficulties with the use of a child safety seat in a high-risk population for nonuse. These concepts can be explored by clinicians and others who work to increase consistent child safety seat use. Additional evaluation and development of the instrument requires validation for its use as a screening or educational tool.
Influenza and Other Respiratory Virus–Related Emergency Department Visits Among Young Children
Authors: Bourgeois Florence T. , Valim Clarissa , Wei Jennie C. , McAdam Alexander J. , Mandl Kenneth D.
Published: July 2006

BACKGROUND. Influenza and other winter respiratory viruses cause substantial morbidity among children. Previous estimates of the burden of illness of these viruses have neglected to include the emergency department, where a large number of patients seek acute care for respiratory illnesses. This study provides city- and statewide population estimates of the burden of illness attributable to respiratory viruses for children receiving emergency department–based care for respiratory infections during the winter months.

METHODS. The number of patients ≤7 years of age presenting to the emergency department of an urban tertiary care pediatric hospital with acute respiratory infections was estimated by using a classifier based on presenting complaints. The rates of specific viral infections in this population were estimated by using the rates of positivity for respiratory syncytial virus, influenza virus, parainfluenza virus, adenovirus, and enterovirus. Local emergency department market share and US Census data enabled determination of the rates of emergency department visits in the Boston, Massachusetts, area and in Massachusetts.

RESULTS. During the 11-year study period, the mean yearly number of patients ≤7 years of age presenting to the study emergency department during the winter season was 17397. On the basis of the respiratory classifier, the mean number of patients with an acute respiratory infection was 6923, or 398 per 1000 emergency department visits. In the city population, the mean number of emergency department visits for acute respiratory infections was 17906, which is equivalent to 113.9 per 1000 children residing in the city, and in the state population the mean number was 61529, or 94.5 per 1000 children residing in the state. At the state level, 23114 of the visits were for respiratory syncytial virus, 5650 for influenza, 1751 for parainfluenza virus, 2848 for adenovirus, and 798 for enterovirus. For patients 6 to 23 months of age in the state population, there were 19860 emergency department visits for acute respiratory infections, or 168 per 1000 children in this age group, with 6235 visits resulting from respiratory syncytial virus and 2112 resulting from influenza.

CONCLUSION. There is a high incidence of emergency department visits for infectious respiratory illnesses among children. This important component of health care use should be included in estimates of the burden of illness attributable to influenza and other winter respiratory viruses.
Pediatric Minimal-Access Surgery: Update 2006
Authors: Zitsman Jeffrey L.
Published: July 2006

Pediatric patients continue to benefit from the advances made in minimal-access surgery. Improvements in techniques and tools have made minimal-access procedures increasingly available to children. Growing popularity of laparoscopy and thoracoscopy has resulted in greater numbers of patients available for outcomes analysis. Randomized, controlled studies have been difficult to perform because of parent, patient, and physician selection bias.
Clinical Features Affecting Final Adult Height in Patients With Pediatric-Onset Crohn's Disease
Authors: Sawczenko Andrew , Ballinger Anne B. , Savage Martin O. , Sanderson Ian R.
Published: July 2006

BACKGROUND. Growth failure is a recognized complication of pediatric-onset Crohn's disease, but there are few data on final adult height.

OBJECTIVE. Our purpose with this work was to determine adult height and the clinical features that influence long-term growth impairment.

METHODS. We retrospectively studied 123 patients with Crohn's disease (65 male and 58 female) who had reached adult height. All of the case subjects were diagnosed before age 16.0 years. Heights were converted to SD scores and univariate analysis performed of factors postulated to influence final height, that is, interval from onset of symptoms to diagnosis, prepubertal onset of symptoms, gender, jejunal disease present at diagnosis, systemic steroid therapy, intestinal surgery, and midparental height SD scores. Significant univariate factors were additional analyzed in regression models.

RESULTS. Mean height deficit at diagnosis was −0.50 SD scores, which improved to −0.29 SD scores at final height. Mean final height compared with target height, calculated from parental height, was −2.4 cm (range: −20.0 to 9.0 cm). Nineteen percent of the case subjects achieved a final height >8.0 cm below target height. The length of the interval between symptom onset and diagnosis correlated negatively with height SD scores at diagnosis. Height SD scores at diagnosis were related to final height SD scores, independent of midparental height. The presence of jejunal disease was negatively related to final height.

CONCLUSIONS. Mean final adult height showed a modest deficit compared with target height, but in one fifth of patients, final height was significantly less than target height. Earlier diagnosis and improved treatment of jejunal disease would be likely to improve final height.
Force platform evaluation of lameness severity following extracorporeal shock wave therapy in horses with unilateral forelimb lameness
Authors: Dahlberg Jessica A. , McClure Scott R. , Evans Richard B. , Reinertson Eric L.
Published: July 2006

Objective—To measure alterations in lameness severity that occur following use of extracorporeal shock wave therapy (ESWT) in horses with naturally occurring unilateral forelimb lameness.

Design—Nonrandomized clinical trial.

Animals—9 horses with unilateral forelimb lameness.

Procedures—Force platform gait analysis was performed prior to administration of any treatments (baseline) and after use of local anesthesia to eliminate the lameness. Extracorporeal shock wave therapy was then administered, and gait analysis was repeated 8 hours later and then daily for 7 days.

Results—Compared with the baseline value, peak vertical force was significantly increased 8 hours and 2 days after ESWT, and peak vertical force on day 2 was not significantly different from force measured after use of local anesthesia to eliminate the lameness. Similarly, vertical impulse was significantly increased, compared with the baseline value, 8 hours and 2 days after ESWT, but at all times, it was significantly lower than vertical impulse measured after use of local anesthesia.

Conclusions and Clinical Relevance—Results suggest that in horses with naturally occurring lameness, use of ESWT results in a period of acute improvement in lameness severity that typically persists for 2 days. Thus, in horses undergoing ESWT, exercise should be controlled for a minimum of 2 days after treatment to prevent further injury.
Clinical aspects of natural infection with Blastomyces dermatitidis in cats: 8 cases (1991–2005)
Authors: Gilor Chen , Graves Thomas K. , Barger Anne M. , O'Dell-Anderson Kristen
Published: July 2006

Objective—To evaluate clinical and laboratory findings, treatment, and clinical outcome in cats with blastomycosis.

Design—Retrospective case series.

Animals—8 cats with naturally occurring blastomycosis.

Procedures—Medical records of the University of Illinois Veterinary Teaching Hospital were searched for cases of blastomycosis in cats diagnosed via cytologic or histopathologic findings. Clinical and laboratory findings, treatment, and clinical outcome were determined. Radiographs were reviewed for the 8 cases.

Results—All cats were systemically ill. Respiratory tract signs and dermal lesions were most commonly observed. All cats had radiographic evidence of respiratory tract disease. Seven of the 8 cats had ill-defined soft-tissue opacities (nodules or masses) or alveolar consolidation of the lungs. Antemortem diagnosis was achieved cytologically in 6 of the 8 cats, and 3 were successfully treated and survived.

Conclusions and Clinical Relevance—In contrast to previous reports, diagnosis was achieved antemortem in most of the cats (all by cytologic identification of the organism). Clinical signs, laboratory findings, and outcome were similar to previous descriptions of this rare disease in cats.
Screening of subtelomeric rearrangements in autistic disorder: Identification of a partial trisomy of 13q34 in a patient bearing a 13q;21p translocation
Authors: Di Bella Maria Antonietta , Calì Francesco , Seidita Gregorio , Mirisola Mario , Ragusa Angela , Ragalmuto Alda , Galesi Ornella , Elia Maurizio , Greco Donatella , Zingale Marinella , Gambino Giovanna , D'Anna Rosalba P. , Regan Regina , Carbone Maria Carmela , Gallo Alessia , Romano Valentino
Published: July 2006

Within the framework of a FISH screening protocol to detect cryptic subtelomeric rearrangements in autistic disorder (AD), a patient bearing three copies of the subtelomeric portion of the q arm of chromosome 13 has been identified. Beside AD, the patient also has severe mental retardation and displays several dysmorphic features. Further FISH analyses revealed that the trisomy was caused by the translocation of a 13q subtelomeric fragment to the acrocentric tip of one chromosome 21 [46,XY.ish der(21) t(13;21) (q34;p13)(D13S1825+)]. Gene dosage experiments carried out with three multiallelic polymorphisms of the subtelomeric region of chromosome 13q showed that the putative length of the triplicate region does not exceed 300 kb about, that is, the distance from telomere to the first normally inherited marker. In addition, gene dosage analysis performed on the derivative chromosome 21, did not reveal loss of the most telomeric protein‐encoding genes on 21p. The potential relationship between a postulated increased expression of genes on 13q34 and the complex phenotype in this trisomic patient is discussed. © 2006 Wiley‐Liss, Inc.
Exploring an interaction of adenosine A2A receptor variability with coffee and tea intake in Parkinson's disease
Authors: Tan E.K. , Lu Z.Y. , Fook‐Chong S.M.C. , Tan E. , Shen H. , Chua E. , Yih Y. , Teo Y.Y. , Zhao Y.
Published: July 2006

Caffeine is an adenosine receptor A1 and A2A receptor antagonist and a putative functional genetic variant of the A2A receptor (2592C > Tins) mediates caffeine‐induced anxiety. Here we investigated the potential interaction of this A2A genetic variant with the quantity of coffee and tea intake and their relationship with the risk of PD. A total of 441 subjects consisting of 222 PD and 219 race, gender and age matched controls were included. A multivariate analysis of the variables including the 2592C > Tins A2A genotypes, age of onset, gender, and the quantity of tea and coffee intake, interaction of the A2A genotypes with coffee intake, interaction of A(2)A genotypes with tea intake demonstrated the quantity of coffee intake to be significantly associated with PD (P < 0.0005, OR = 0.922, 95% CI: 0.881, 0.964). However, there was no significant interaction of the A2A genotypes with the quantity of coffee and tea intake in modulating the risk of PD. The dose dependent protective effect of coffee intake in PD was independent of the 2592C > Tins A2A genotype suggesting that the pharmacogenetic action of caffeine in PD may be mediated differently from other caffeine‐induced neurologic syndromes. © 2006 Wiley‐Liss, Inc.
NOS2A and the modulating effect of cigarette smoking in Parkinson's disease
Authors: Hancock Dana B. , Martin Eden R. , Fujiwara Kenichiro , Stacy Mark A. , Scott Burton L. , Stajich Jeffrey M. , Jewett Rita , Li Yi‐Ju , Hauser Michael A. , Vance Jeffery M. , Scott William K.
Published: July 2006

Objective

Inducible nitric oxide synthase, a protein product of NOS2A, generates nitric oxide as a defense mechanism, but excessive levels threaten cellular survival. NOS2A is a candidate gene for Parkinson's disease (PD) that potentially interacts with cigarette smoking. We examined NOS2A for association with PD risk and age at onset (AAO) and for interaction with smoking.

Methods

We genotyped 13 NOS2A single nucleotide polymorphisms (SNPs) in 466 singleton families and in a validation set of 286 multiplex families. We tested allelic and haplotypic association using the association in the presence of linkage test, genotypic associations using the genotype pedigree disequilibrium test, AAO effects using the quantitative transmission disequilibrium test, and interactions using generalized estimating equations.

Results

Among the pooled earliest onset families, rs2255929 and rs1060826 generated significant allelic (p = 0.000059 and 0.0062, respectively) and genotypic (p = 0.0039 and 0.0014, respectively) associations with risk and AAO (p = 0.00070 and 0.0073, respectively); the two‐SNP haplotype generated even stronger association with PD (p = 0.000013). Significant interactions with smoking (p = 0.0015 for rs 2255929 and p < 0.0001 for rs 1060826) were detected in a subset of the families; smoking was inversely associated with PD among risk allele noncarriers, but significance diminished among carriers.

Interpretation

Our findings support NOS2A as a genetic risk factor in PD, potentially by influencing AAO and by modifying the inverse association between PD and smoking. Ann Neurol 2006
Solution structures and characterization of human immunodeficiency virus Rev responsive element IIB RNA targeting zinc finger proteins
Authors: Mishra Subrata H. , Shelley Christopher M. , Barrow Doyle J. , Darby Martyn K. , Germann Markus W.
Published: July 2006

The Rev responsive element (RRE), a part of unspliced human immunodeficiency virus (HIV) RNA, serves a crucial role in the production of infectious HIV virions. The viral protein Rev binds to RRE and facilitates transport of mRNA to the cytoplasm. Inhibition of the Rev–RRE interaction disrupts the viral life cycle. Using a phage display protocol, dual zinc finger proteins (ZNFs) were generated that bind specifically to RREIIB at the high affinity Rev binding site. These proteins were further shortened and simplified, and they still retained their RNA binding affinity. The solution structures of ZNF29 and a mutant, ZNF29G29R, have been determined by nuclear magnetic resonance (NMR) spectroscopy. Both proteins form C2H2‐type zinc fingers with essentially identical structures. RNA protein interactions were evaluated quantitatively by isothermal titration calorimetry, which revealed dissociation constants (Kd's) in the nanomolar range. The interaction with the RNA is dependent upon the zinc finger structure; in the presence of EDTA, RNA binding is abolished. For both proteins, RNA binding is mediated by the α‐helical portion of the zinc fingers and target the bulge region of RREIIB‐TR. However, ZNF29G29R exhibits significantly stronger binding to the RNA target than ZNF29; this illustrates that the binding of the zinc finger scaffold is amenable to further improvements. © 2006 Wiley Periodicals, Inc. Biopoly 83:352–364, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Anion Binding versus Intramolecular Hydrogen Bonding in Neutral Macrocyclic Amides
Authors: Chmielewski Michał J. , Jurczak Janusz
Published: July 2006

Although amide groups are important hydrogen‐bond donors in natural and synthetic anion receptors, studies on structure–affinity relationships of amide‐based macrocyclic receptors are still very limited. Therefore, we synthesized a series of macrocyclic tetraamides 5–8 derived from 1,3‐benzenedicarboxylic (isophthalic) acid and aliphatic α,ω‐diamines of different lengths. 1H NMR titrations in DMSO solution show that the anion affinity of these receptors decreases with increasing size of the macrocycle irrespective of the anion, and this suggests a minor role of geometric complementarity. Comparison with their previously studied pyridine congeners reveals that the isophthalic acid based macrocycles are less potent, in contrast to what was found for simple model diamides. Combined theoretical and experimental structural studies were carried out to determine the reasons behind this behaviour. The results show that the unexpectedly low anion binding ability of the isophthalic acid‐based receptors is due to the self‐complementary nature of the isophthalic bis‐amide fragments: when two such moieties are present within a sufficiently flexible macrocycle, they adopt syn–anti conformations and bind each other by two strong intramolecular hydrogen bonds that close the macrocyclic cavity. Nevertheless, anion binding is able to break these hydrogen bonds and switch a macrocycle into a convergent all‐syn conformation. Despite the ill‐preorganized conformation, 20‐membered receptor 6 is better than either its open‐chain analogue (macrocyclic effect) and/or its isomer having differently placed carbonyl groups. The crystal structures of four anion complexes of the macrocyclic receptors are reported. X‐ray studies and solution NMR data confirmed the inclusive nature of the complexes and pointed to strong involvement of aromatic CH hydrogen atoms in anion binding.
C20 Carbon Clusters: Fullerene–Boat–Sheet Generation, Mass Selection, Photoelectron Characterization
Authors: Prinzbach Horst , Wahl Fabian , Weiler Andreas , Landenberger Peter , Wörth Jürgen , Scott Lawrence T. , Gelmont Marc , Olevano Daniela , Sommer Frank , von Issendorff Bernd
Published: July 2006

Electron‐impact ionization in a time‐of‐flight mass spectrometer of C20H0–3Br14–12 probes—secured from C20H20 dodecahedrane by a “brute‐force” bromination protocol—provided bromine‐free C20H0–2(3) anions in amounts that allowed the clean mass‐separation of the hydrogen‐free C20− ions and the photoelectron (PE) spectroscopic characterization as C20 fullerene (electron affinity (EA)=2.25±0.03 eV, vibrational progressions of 730±70). The extremely strained C20 fullerene ions surfaced as kinetically rather stable entities (lifetime of at least the total flight time of 0.4 ms); they only very sluggishly expel a C2 unit. The HOMO and LUMO are suggested to be almost degenerate (ΔE=0.27 eV). The assignment as a fullerene was corroborated by the PE characterization of the C20 bowl (EA=2.17±0.03 eV, vibrational progression of 2060±50 cm−1) analogously generated from C20H10 corannulene (C20H1–3Br9–8 samples) and comparably stable. Highly resolved low‐temperature PE spectra of the known C20 ring (EA=2.49±0.03 eV, vibrational progressions 2022±45 and 455±30 cm−1), obtained from graphite, display an admixture of, most probably, a bicyclic isomer (EA=3.40±0.03 eV, vibrational progression 455±30 cm−1). The C20+(−) and C20H2+(−) cluster ions generated from polybrominated perylene (C20H0–2Br12–10) have (most probably) retained the planar perylene‐type skeleton (sheet, EA=2.47±0.03 eV, vibrational progressions of 2089±30 and 492±30 cm−1 and EA=2.18±0.03 eV, vibrational progressions of 2105±30 and 468±30 cm−1).
Synthesis and Electrochemical Properties of Semicrystalline Gyroidal Mesoporous MnO2
Authors: Zhou Qin , Li Xiang , Li Yan‐Guang , Tian Bo‐Zhi , Zhao Dong‐Yuan , Jiang Zhi‐Yu
Published: July 2006

Mesoporous silica KIT‐6 has novel three‐dimensional gyroidal channel structure, space group of Ia‐3d, and ordered tunable pores up to 10 nm. In this paper, such mesostructured silica was employed as hard template to prepare semicrystalline gyroidal mesoporous MnO2. The structure was investigated by XRD, TEM and HRTEM, and found to be of high quality Ia‐3d symmetry, in good accordance with the template structure. The material has a BET surface of 118 m2·g‐1 and pore volume of 0.35 cm3·g−1 after eliminating template. Mesoporous MnO2 has shown good electrochemical property as supercapacitor material in 1 mol·L−1 Na2SO4 and 1 mol·L−1 LiClO4 solutions, but interesting pseudocapacitance behavior was observed in the case of 6 mol·L−1 KOH. It was found that mesoporous MnO2 performed stable reversible electrochemical behavior with capacitance of 220 F·g−1 in a potential range of −0.1–0.55 V vs. Hg/HgO in alkaline solution, demonstrating that it is a promising novel electrode material for the fabrication of electrochemical capacitors.
Highly Selective Salicylate Membrane Electrode Based onN,N′‐(Aminoethyl)ethylenediamide Bis(2‐salicylideneimine) Binuclear Copper(II) Complex as Neutral Carrier
Authors: Sun Ai‐Li , Cai Ya‐Qin , Yuan Ruo , Gui Guo‐Feng
Published: July 2006

A new ion selective electrode for salicylate based onN,N′‐(aminoethyl)ethylenediamide bis(2‐salicylideneimine) binuclear copper(II) complex [Cu(II)2‐AEBS] as an ionophore was developed. The electrode has a linear range from 1.0×10−1to 5.0×10−7mol·L−1with a near‐Nernstian slope of (−55±1) mV/decade and a detection limit of 2.0×10−7mol·L−1in phosphorate buffer solution of pH 5.0 at 25 °C. It shows good selectivity for Sal−and displays anti‐Hofmeister selectivity sequence:Sal−>SCN−>ClO−4>I−>NO−2>Br−>NO−3>Cl−>SO2−3>SO2−4. The proposed sensor based on binuclear copper(II) complex has a fast response time of 5–10 s and can be used for at least 2 months without any major deviation. The response mechanism is discussed in view of the alternating current (AC) impedance technique and the UV‐vis spectroscopy technique. The effect of the electrode membrane compositions and the experimental conditions were studied. The electrode has been successfully used for the determination of salicylate ion in drug pharmaceutical preparations.
Validation of the functional assessment of cancer therapy esophageal cancer subscale
Authors: Darling Gail , Eton David T. , Sulman Joanne , Casson Alan G. , Cella David
Published: July 2006

BACKGROUND.

To develop and validate a quality of life subscale for patients with esophageal cancer to be used with the Functional Assessment of Cancer Therapy—General (FACT‐G).

METHODS.

Prospective cohort study of patients with esophageal cancer treated with surgery alone or neoadjuvant chemoradiotherapy and surgery evaluating the validity, internal consistency, and responsiveness to change of the FACT‐Esophageal (FACT‐E) when comparing it with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ 30) and esophageal (OES 24) as well as clinical factors.

RESULTS.

The FACT‐E demonstrated very good convergent and divergent validity when compared with the EORTC QLQ30 and OES 24 and clinical variables. Internal consistency was also good with coefficient α >0.70 for all subscales and individual items. Stability coefficients were >0.80. Changes in clinical status were reflected in changes in FACT‐E scores demonstrating responsiveness to change, particularly in patients receiving neoadjuvant chemoradiotherapy before surgery.

CONCLUSIONS.

The FACT‐E met or exceeded all standards for validity, providing an option to measure health‐related quality of life for different treatment strategies for esophageal cancer. Cancer 2006. © 2006 American Cancer Society.
Variations in reconstruction after radical cystectomy
Authors: Gore John L. , Saigal Christopher S. , Hanley Jan M. , Schonlau Matthias , Litwin Mark S. ,   and the Urologic Diseases in America Project
Published: July 2006

BACKGROUND.

Most urologists specializing in the management of patients with bladder cancer consider continent urinary diversion the reconstructive technique that affords the best quality of life after radical cystectomy. The authors sought to evaluate factors that predict reconstructive technique after radical cystectomy.

METHODS.

Using linked data from Medicare and the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program, 3611 subjects were identified who underwent radical cystectomy for bladder cancer between 1992 and 2000. Multivariate logistic regression was used to identify factors independently associated with utilization of continent reconstruction after radical cystectomy, incorporating patient and provider variables.

RESULTS.

In multivariate analysis, the likelihood of continent diversion was inversely associated with older age (odds ratio [OR] ≤0.68, P ≤ .002), African American race (OR 0.43, P = .003), and higher comorbidity index (OR 0.71, P = .03), and directly associated with male sex (OR 1.45, P = .002), higher education level (OR 1.54, P = .03), and year of surgery (OR ≥ 1.56, P < .001 for all year categories vs. 1992–1994). Treatment at academic (OR 1.43, P = .003) and NCI‐designated cancer centers (OR 5.50, P < .001) and by high‐volume providers (OR 1.49, P < .001) was independently associated with continent reconstruction.

CONCLUSIONS.

Disparities in the utilization of continent urinary diversion after radical cystectomy suggest that demographic, socioeconomic, provider‐based, and clinical variables predict the likelihood that those undergoing radical cystectomy will receive continent reconstruction. Regionalization of bladder cancer care may ameliorate many of the disparities noted but must be balanced against the risk imposed by a delay in care. Cancer 2006. © 2006 American Cancer Society.
Nucleation and Growth of Boron Nanowires on ZrB2 Particles
Authors: Guo L. , Singh R. N. , Kleebe H.‐J.
Published: July 2006

Amorphous boron rich nanowires are grown on ZrB2 particles using diborane as the gas precursor in a CVD process under 20 Torr pressure and at 900 °C. These nanowires have uniform diameters of tens of nanometers and lengths of up to several micrometers. The boron‐rich nanowires are characterized and found to be composed of boron clusters containing unit cells of icosahedral B12. A surface nucleation and growth mechanism of solid boron from vapor phase is proposed to explain the nanowire growth. The role of ZrB2 particles in the synthesis of the boron‐rich nanostructures is also discussed.
Algebraic multigrid and incompressible fluid flow
Authors: Webster R.
Published: July 2006

This paper is concerned with the development of algebraic multigrid (AMG) solution methods for the coupled vector–scalar fields of incompressible fluid flow. It addresses in particular the problems of unstable smoothing and of maintaining good vector–scalar coupling in the AMG coarse‐grid approximations. Two different approaches have been adopted. The first is a direct approach based on a second‐order discrete‐difference formulation in primitive variables. Here smoothing is stabilized using a minimum residual control harness and velocity–pressure coupling is maintained by employing a special interpolation during the construction of the inter‐grid transfer operators. The second is an indirect approach that avoids the coupling problem altogether by using a fourth‐order discrete‐difference formulation in a single scalar‐field variable, primitive variables being recovered in post‐processing steps. In both approaches the discrete‐difference equations are for the steady‐state limit (infinite time step) with a fully implicit treatment of advection based on central differencing using uniform and non‐uniform unstructured meshes. They are solved by Picard iteration, the AMG solvers being used repeatedly for each linear approximation.

Both classical AMG (C‐AMG) and smoothed‐aggregation AMG (SA‐AMG) are used. In the direct approach, the SA‐AMG solver (with inter‐grid transfer operators based on mixed‐order interpolation) provides an almost mesh‐independent convergence. In the indirect approach for uniform meshes, the C‐AMG solver (based on a Jacobi‐relaxed interpolation) provides solutions with an optimum scaling of the convergence rates. For non‐uniform meshes this convergence becomes mesh dependent but the overall solution cost increases relatively slowly with increasing mesh bandwidth. Copyright © 2006 John Wiley & Sons, Ltd.
Alluvial geoarchaeology of a Middle Archaic Mound complex in the lower Mississippi Valley, U.S.A.
Authors: Arco Lee J. , Adelsberger Katherine A. , Hung Ling‐yu , Kidder Tristram R.
Published: July 2006

The Nolan site (16MA201), 14C dated 5200–4800 cal yr B.P. and located in the Tensas Basin of northeastern Louisiana, is the only recorded Middle Archaic mound site in the alluvial valley of the Mississippi River. Alluvial deposition has buried the Nolan site under 3–4 m of Holocene sediment, prohibiting traditional excavation of the site. Because data are unattainable by other means, soil coring and subsequent stratigraphic and sedimentological analyses permit reconstruction of the natural and cultural depositional history of the Nolan site. The sedimentary characteristics of basal deposits within cores suggest the presence of an Arkansas River paleochannel immediately adjacent to the site. Chronostratigraphic data show this channel was no longer active by ca. 5200 cal yr B.P. Contrary to existing models, the Arkansas River Meander Belt 4 and the Mississippi River Meander Belt 4 are not the same age. Microartifact and losson‐ignition analyses of sediment identify natural versus cultural strata and permit the identification of artificial constructions—including four earthen mounds and one earthen ridge—at the Nolan site. Overbank sediments attributed to a mapped Mississippi River Stage 4 meander belt are dated ca. 4800–3800 cal yr B.P. This age is considerably younger than previous estimates and demonstrates the existing chronological models for Mississippi River meander belts must be carefully assessed. Core analyses also reveal flood‐related crevasse splays deposited throughout the Tensas Basin after the occupation of the Nolan site. These deposits serve as relative chronological indicators and aid in stratigraphic assessments of the Nolan site. Reconstruction of the earthworks and their stratigraphic context reveals one of the largest and earliest Middle Archaic mound sites in North America. © 2006 Wiley Periodicals, Inc.