bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of Parahippocampal Representation in the Absence of Stimulus Input Enhances Long-Term Encoding: A Functional Magnetic Resonance Imaging Study of Subsequent Memory after a Delayed Match-to-Sample Task
Authors: Schon Karin , Hasselmo Michael E. , LoPresti Matthew L. , Tricarico Marisa D. , Stern Chantal E.
Published: December 2004

Recent theoretical models based on cellular processes in parahippocampal structures show that persistent neuronal spiking in the absence of stimulus input is important for encoding. The goal of this study was to examine in humans how sustained activity in the parahippocampal gyrus may underlie long-term encoding as well as active maintenance of novel information. The relationship between long-term encoding and active maintenance of novel information during brief memory delays was studied using functional magnetic resonance imaging (fMRI) in humans performing a delayed matching-to-sample (DMS) task and a post-scan subsequent recognition memory task of items encountered during DMS task performance. Multiple regression analyses revealed fMRI activity in parahippocampal structures associated with the active maintenance of trial-unique visual information during a brief memory delay. In addition to a role in active maintenance, we found that the subsequent memory for the sample stimuli as measured by the post-scan subsequent recognition memory task correlated with activity in the parahippocampal gyrus during the delay period. The results provide direct evidence that encoding mechanisms are engaged during brief memory delays when novel information is actively maintained. The relationship between active maintenance during the delay period and long-term subsequent memory is consistent with current theoretical models and experimental data that suggest that long-term encoding is enhanced by sustained parahippocampal activity.
Fluorescent Proteins Expressed in Mouse Transgenic Lines Mark Subsets of Glia, Neurons, Macrophages, and Dendritic Cells for Vital Examination
Authors: Zuo Yi , Lubischer Jane L. , Kang Hyuno , Tian Le , Mikesh Michelle , Marks Alexander , Scofield Virginia L. , Maika Shan , Newman Craig , Krieg Paul , Thompson Wesley J.
Published: December 2004

To enable vital observation of glia at the neuromuscular junction, transgenic mice were generated that express proteins of the green fluorescent protein family under control of transcriptional regulatory sequences of the human S100B gene. Terminal Schwann cells were imaged repetitively in living animals of one of the transgenic lines to show that, except for extension and retraction of short processes, the glial coverings of the adult neuromuscular synapse are stable. In other lines, subsets of Schwann cells were labeled. The distribution of label suggests that Schwann cells at individual synapses are clonally related, a finding with implications for how these cells might be sorted during postnatal development. Other labeling patterns, some present in unique lines, included astrocytes, microglia, and subsets of cerebellar Bergmann glia, spinal motor neurons, macrophages, and dendritic cells. We show that lines with labeled macrophages can be used to follow the accumulation of these cells at sites of injury.
Behavioral Stress Modifies Hippocampal Synaptic Plasticity through Corticosterone-Induced Sustained Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Activation
Authors: Yang Chih-Hao , Huang Chiung-Chun , Hsu Kuei-Sen
Published: December 2004

The induction of hippocampal long-term synaptic plasticity is exquisitely sensitive to behavioral stress, but the underlying mechanisms are still unclear. We report here that hippocampal slices prepared from adult rats that had experienced unpredictable and inescapable restraint tail-shock stress showed marked impairments of long-term potentiation (LTP) in the CA1 region. The same stress promoted the induction of long-term depression (LTD). These effects were prevented when the animals were given the glucocorticoid receptor antagonist 11β, 17β-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)-estra-4-9-dien-3-one before the stress. Immunoblotting analyses revealed that stress induced a profound and prolonged extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK1/2 MAPK) hyperphosphorylation through small GTPase Ras, Raf-1, and MAPK kinase 1/2 (MEK1/2). Furthermore, the stress effects were obviated by the intrahippocampal injection of specific inhibitors of MEK1/2 (U0126), protein kinase C (bisindolylmaleimide I), tyrosine kinase (K252a), and BDNF antisense oligonucleotides. These results suggest that the effects of stress on LTP and LTD originate from the corticosterone-induced sustained activation of ERK1/2-coupled signaling cascades.
Synthesis of 1,3‐Dienes from Alkynes and Ethylene: Acetic Acid 2‐Methylene‐3‐phenethylbut‐3‐enyl Ester
Authors: Mori Miwako , Tonogaki Keisuke , Kinoshita Atsushi
Published: December 2004

(4, 4‐Dibromobut‐3‐enyl)benzene

5‐Phenylpent‐2‐yl‐1‐ol

Acetic acid 5‐phenylpent‐2‐ynyl ester

Acetic acid 2‐methylene‐3‐phenethylbut‐3‐enyl ester

Butyllithium
Platinum Catalyzed Hydrosilylation and Palladium Catalyzed Cross‐Coupling: One‐Pot Hydroarylation of 1‐Heptyne to (
E
)‐1‐(1‐Heptenyl)‐4‐methoxybenzene
Authors: Denmark Scott E. , Wang Zhigang
Published: December 2004

1‐Heptyne

(
E)
‐1‐Heptenyl‐4‐methoxybenzene

Platinum(0)‐1,3‐divinyl‐1,1,3,3,‐tetramethyldisiloxane complex

Palladium chloride
Preparation of 2,4‐Disubstituted Imidazoles: 4‐(4‐Methoxyphenyl)‐2‐phenyl‐1H‐imidazole
Authors: Li Bryan , Chiu Charles K‐F , Hank Richard F. , Murry Jerry , Roth Joshua , Tobiassen Harry
Published: December 2004

4‐(4‐Methoxyphenyl)‐2‐phenyl‐1H‐imidazole

Benzamidine hydrochloride

4‐Methoxyphenacyl bromide
Preparation of

N

‐Aryl‐5
R
‐Hydroxymethyl‐2‐Oxazolidinones from
N
‐Aryl Carbamates:
N
‐Phenyl‐(5
R
)‐Hydroxymethyl‐ 2‐Oxazolidinone
Authors: Manninen Peter R. , Brickner Steven J.
Published: December 2004

N
‐Phenyl‐5
R‐
hydroxymethyl‐2‐oxazolidinone

N‐Phenylcarbamic acid methyl ester

n
‐Butyllithium

Glycidyl butyrate
Synthesis of Ortho Substituted Arylboronic Esters by in situ Trapping of Unstable Lithio Intermediates: 2‐(5,5‐Dimethyl‐1,3,2‐dioxaborinan‐2‐yl)benzoic Acid Ethyl Ester
Authors: Langgaard Kristensen Jesper , Lysén Morten , Vedsø Per , Begtrup Mikael
Published: December 2004

2‐(5, 5‐Dimethyl‐1,3,2‐dioxaborinan‐2‐yl)benzoic acid ethyl ester

2, 2, 6, 6‐Tetramethylpiperdine

n‐
Butyllithium

Trisiopropyl borate
Synthesis of 9‐Spiroepoxy‐

endo

‐tricyclo[5.2.2.0
2,6
]undeca‐4,10‐dien‐8‐one
Authors: Singh* Vishwakarma , Porinchu Mini , Vedantham Punitha , Sahu Pramod K.
Published: December 2004

9‐Spiroepoxy‐endo‐tricyclo[5.2.2.0 2.6]undeca‐4,10‐dien‐8‐one

Sodium metaperiodate
Indium/Ammonium Chloride‐Mediated Selective Reduction of Aromatic Nitro Compounds: Ethyl 4‐aminobenzoate
Authors: Banik Bimal K. , Banik Indrani , Becker Frederick F.
Published: December 2004

Ethyl‐4‐aminobenzoate

Ethyl‐4‐nitrobenzoate

Ammonium chloride

Indium
Methyltrioxorhenium Catalyzed Oxidation of Secondary Amines to Nitrones:

N

‐Benzylidene‐benzylamine

N

‐Oxide
Authors: Goti Andrea , Cardona Francesca , Soldaini Gianluca
Published: December 2004

N‐
Benzylidene‐benzylamine N‐oxide

Methyltrioxorhenium

Urea hydrogen peroxide

Dibenzylamine
Synthesis and Use of Glycosyl Phosphates as Glycosyl Donors
Authors: Love Kerry R. , Seeberger Peter H.
Published: December 2004

Dibutyl 3, 4, 6‐tri‐
O
‐benzyl‐2‐
O‐
pivaloyl‐D‐glucopyranosyl phosphate

3,4,6‐Tri‐
O
‐benzyl‐D‐glucal

3,4,6‐Tri‐
O‐
benzyl‐2‐
O‐
pivaloyl‐beta‐D‐glucopyranosyl‐(1→6)‐1,2:3,4‐di‐
O‐
isopropylidiene‐alpha‐D‐galactopyranoside

1,2:3,4‐Di‐
O‐
isopropylylidene‐alpha‐D‐galactopyranose
CC and CXC chemokine receptors mediate migration, proliferation, and matrix metalloproteinase production by fibroblast‐like synoviocytes from rheumatoid arthritis patients
Authors: García‐Vicuña Rosario , Gómez‐Gaviro Maria Victoria , Domínguez‐Luis Maria Jesús , Pec Martina K. , González‐Alvaro Isidoro , Alvaro‐Gracia Jose María , Díaz‐González Federico
Published: December 2004

Objective

To explore the potential involvement of the chemokine system in synoviocyte‐mediated tissue destruction in rheumatoid arthritis (RA), we studied the expression profile of chemokine receptors and their function in the migration, proliferation, and matrix metalloproteinase (MMP) production of cultured fibroblast‐like synoviocytes (FLS) from RA patients.

Methods

The presence of CC and CXC chemokine receptors on cultured FLS was studied at the messenger RNA (mRNA) level by reverse transcriptase–polymerase chain reaction and at the cell surface expression level by flow cytometry. Variations in cytosolic calcium influx induced by chemokine stimulation were assessed by flow cytometry on Fura Red–preloaded FLS. Two‐compartment transwell chambers were used for FLS chemotaxis assays. Cell growth was measured by a fluorescence‐based proliferation assay. Gelatinase and collagenase activities were determined by a fibril degradation assay and zymography.

Results

FLS constitutively expressed the receptors CCR2, CCR5, CXCR3, and CXCR4, both at the cell surface and mRNA levels, but failed to express CCR3 and CCR6. Significant intracytosolic calcium influx was observed on FLS challenged with monocyte chemotactic protein 1 (MCP‐1), stromal cell–derived factor 1α (SDF‐1α), and interferon‐inducible protein 10 (IP‐10). Stimulation with MCP‐1, SDF‐1α, IP‐10, and monokine induced by interferon‐γ enhanced the migration and proliferation of FLS. These chemokines, in addition to RANTES, increased in a dose‐ and time‐dependent manner the gelatinase and collagenase activities in cell‐free supernatants of cultured FLS. Interestingly, the chemokine‐mediated up‐regulation of MMP activities was significantly abrogated by the presence of anti–interleukin‐1β, but not anti–tumor necrosis factor α, blocking antibodies.

Conclusion

These data suggest that through modulation of the migration, proliferation, and MMP production by FLS, the chemokine system may play a more direct role in the destructive phase of RA than is currently suspected, and thus emphasize the relevance of chemokines and their receptors as potential therapeutic targets in this disease.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXIII. Baseline predictors of vascular events
Authors: Toloza Sergio M. A. , Uribe América G. , McGwin Gerald , Alarcón Graciela S. , Fessler Barri J. , Bastian Holly M. , Vilá Luis M. , Wu Ruihua , Shoenfeld Yehuda , Roseman Jeffrey M. , Reveille John D. ,   for the LUMINA Study Group
Published: December 2004

Objective

To determine the baseline (time 0) risk factors associated with the subsequent occurrence of vascular events in a multiethnic US cohort (LUMINA [LUpus in MInorities: NAture versus nurture]) of patients with systemic lupus erythematosus (SLE).

Methods

Five hundred forty‐six LUMINA patients were assessed at time 0 for traditional and nontraditional (disease‐related) risk factors for vascular events. These were defined as 1) cardiovascular (myocardial infarction and/or definite or classic angina and/or the undergoing of a vascular procedure for myocardial infarction [coronary artery bypass graft]), 2) cerebrovascular (stroke), and 3) peripheral vascular (arterial claudication and/or gangrene or significant tissue loss and/or arterial thrombosis in peripheral arteries). The observation time (followup time in the cohort) was the interval between time 0 and the last visit. The unit of analysis was the patient and not each vascular event. Variables at time 0 and vascular events were examined by univariable and multivariable (logistic and Cox proportional hazards regression) analyses. Age, sex, ethnicity, followup time, and all known risk factors for the occurrence of vascular events were included in the model.

Results

Thirty‐four patients (6.2%) developed one or more vascular event after time 0. The overall median duration of followup in the cohort was 73.8 months (range 10.8–111.3 months). Vascular events (13 cardiovascular, 18 cerebrovascular, 5 peripheral vascular) occurred in 7 Hispanics from Texas (6.5%), 1 Hispanic from Puerto Rico (1.2%), 15 African Americans (7.5%), and 11 Caucasians (7.1%). The mean total number of traditional risk factors was significantly higher in patients who developed vascular events than in those who did not (7.1 versus 5.6). Independent predictors of vascular events were older age, current smoking status, longer followup time, elevated serum levels of C‐reactive protein (CRP), and the presence of any antiphospholipid antibody. The same variables were identified when time‐dependent analyses were performed, although azathioprine use was also found to be a contributing factor.

Conclusion

Smoking, previously not reported in SLE, emerged as a predictor of vascular events and should be strongly discouraged. Antiphospholipid antibodies and CRP support the role of inflammation and autoimmunity in the development of accelerated atherosclerosis in SLE. Ethnicity was not associated with vascular events in our patients.
Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist
Authors: Korn J. H. , Mayes M. , Matucci Cerinic M. , Rainisio M. , Pope J. , Hachulla E. , Rich E. , Carpentier P. , Molitor J. , Seibold J. R. , Hsu V. , Guillevin L. , Chatterjee S. , Peter H. H. , Coppock J. , Herrick A. , Merkel P. A. , Simms R. , Denton C. P. , Furst D. , Nguyen N. , Gaitonde M. , Black Carol ,   RAPIDS‐1 Study Group
Published: December 2004

Objective

Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis (SSc; scleroderma) and lead to pain, impaired function, and tissue loss. We investigated whether treatment with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcers in patients with SSc.

Methods

This was a randomized, prospective, placebo‐controlled, double‐blind study of 122 patients at 17 centers in Europe and North America, evaluating the effect of treatment on prevention of digital ulcers. The primary outcome variable was the number of new digital ulcers developing during the 16‐week study period. Secondary assessments included healing of existing digital ulcers and evaluation of hand function using the Scleroderma Health Assessment Questionnaire.

Results

Patients receiving bosentan had a 48% reduction in the mean number of new ulcers during the treatment period (1.4 versus 2.7 new ulcers; P = 0.0083). Patients who had digital ulcers at the time of entry in the study were at higher risk for the development of new ulcers; in this subgroup the mean number of new ulcers was reduced from 3.6 to 1.8 (P = 0.0075). In patients receiving bosentan, a statistically significant improvement in hand function was observed. There was no difference between treatment groups in the healing of existing ulcers. Serum transaminase levels were elevated to >3‐fold the upper limit of normal in bosentan‐treated patients; this elevation is comparable with that observed in previous studies of this agent. Other side effects were similar in the 2 treatment groups.

Conclusion

Endothelins may play an important role in the pathogenesis of vascular disease in patients with SSc. Treatment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulcers and improving hand function in patients with SSc.
Expression of Toll‐like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin‐12 and interleukin‐18 via interferon‐γ
Authors: Radstake Timothy R. D. J. , Roelofs Mieke F. , Jenniskens Yvonne M. , Oppers‐Walgreen Birgitte , van Riel Piet L. C. M. , Barrera Pilar , Joosten Leo A. B. , van den Berg Wim B.
Published: December 2004

Objective

To study the expression of Toll‐like receptor 2 (TLR‐2) and TLR‐4 and its association with proinflammatory cytokines in synovial tissue from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals.

Methods

Synovial tissue specimens from 29 RA patients were stained for TLR‐2, TLR‐4, and proinflammatory cytokines (interleukin‐1β [IL‐1β], IL‐12, IL‐17, IL‐18, and tumor necrosis factor α [TNFα]). The expression of TLR‐2, TLR‐4, and cytokines as well as the degree of inflammation in synovial tissue were compared between patients with RA, patients with OA (n = 5), and healthy individuals (n = 3). Peripheral blood mononuclear cells (PBMCs) were incubated with IL‐12 and IL‐18, and TLR expression was assessed using fluorescence‐activated cell sorter analysis. Production of TNFα and IL‐6 was measured using Luminex bead array technology.

Results

In RA synovial tissue, the expression of TLR‐2 was slightly higher than that of TLR‐4. Interestingly, both TLR‐2 and TLR‐4 were expressed at higher levels in moderately inflamed synovium, as compared with synovial tissue with no or severe inflammation. TLR expression in both the lining and the sublining was associated with the presence of IL‐12 and IL‐18, but no other cytokines, in the lining. The expression of both TLRs was low in synovial tissue from OA patients and healthy donors. Stimulation of PBMCs with IL‐12 and IL‐18 resulted in increased expression of both TLR‐2 and TLR‐4; this could be blocked with anti–interferon‐γ (anti‐IFNγ) antibodies, suggesting a role for IFNγ. Lipopolysaccharide‐ or lipoteichoic acid–mediated triggering of PBMCs incubated with IL‐12/IL‐18 or IFNγ led to an increased production of both TNFα and IL‐6, indicating the functionality of TLR‐2 and TLR‐4.

Conclusion

TLR‐2 and TLR‐4 are expressed in synovial tissue of patients with clinically active disease and are associated with the levels of both IL‐12 and IL‐18. The synergistic effect of IL‐12 and IL‐18 on T cell IFNγ production seems to regulate expression of TLR‐2 and TLR‐4 in the synovial tissue of RA patients.
The effect of body weight on progression of knee osteoarthritis is dependent on alignment
Authors: Felson David T. , Goggins Joyce , Niu Jingbo , Zhang Yuqing , Hunter David J.
Published: December 2004

Objective

Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment.

Methods

The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30‐month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0–3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations.

Results

Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2‐unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00–1.16). However, among those knees with neutral alignment (0–2°), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (≥7°), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2‐unit increase in BMI 1.23, 95% CI 1.05–1.45).

Conclusion

Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.
Determinants of discharge destination following elective total hip replacement
Authors: Pablo Paola de , Losina Elena , Phillips Charlotte B. , Fossel Anne H. , Mahomed Nizar , Lingard Elizabeth A. , N. Katz Jeffrey
Published: December 2004

Objective

To identify the factors associated with discharge to an inpatient rehabilitation facility versus discharge directly to home after elective total hip replacement (THR).

Methods

Data were obtained from a medical record review and a cross‐sectional survey of a population‐based cohort of patients who received elective primary or revision THR in 1995. Postoperative functional status was measured as the ability to walk independently prior to discharge. A multivariate regression model was developed with discharge to an inpatient rehabilitation facility versus directly to home as the dependent variable. The model adjusted for demographic characteristics, socioeconomic features, and several preoperative and postoperative clinical factors.

Results

We included 1,276 patients age 65–94 years in the analysis. Of these, 58% were discharged from the acute care hospital to a rehabilitation facility. The cohort had mean age of 73 years; 96% were white; 62% were female; 32% were living alone; 38% had an annual income less than $20,000; and 78% were unable to walk independently in the hospital before discharge. For primary THR patients, multivariate analysis showed a significant association between being discharged to a rehabilitation facility and being unable to walk at discharge, older age, obesity, and living alone. For revision THR patients, multivariate analysis also showed a significant association between being discharged to a rehabilitation facility and being unable to walk at discharge.

Conclusion

In a large population‐based sample, postoperative functional status, age, obesity, and social support all influenced the discharge destination following elective THR.
Eligibility, utilization, and costs in a California Medicaid lupus population
Authors: Nichol Michael B. , Shi Sheng , Knight Tara K. , Wallace Daniel J. , Weisman Michael H.
Published: December 2004

Objective

To investigate whether ethnicity was associated with differences in Medicaid eligibility, health care utilization, and direct medical costs in a systemic lupus erythematosus (SLE) population.

Methods

A retrospective analysis of California Medicaid claims data was conducted on patients with SLE. Patient eligibility and month‐by‐month utilization and costs were computed and compared across ethnic groups. Descriptive statistics are presented. A mixed regression model on patient‐level data was used to verify the trends of the aggregate data, controlling for covariates. A survival regression model on time to ineligibility was used to show eligibility patterns adjusted for covariates.

Results

Hispanic patients were less likely to have a lengthy eligibility period as compared with other cohorts (∼50% versus 70% eligible at month 36, respectively). As treatment progressed, Hispanics generated lower total costs than other cohorts. Results for inpatient frequency, prescription costs, and outpatient/physician/supply (Part B) costs followed similar patterns. Mixed regression model findings revealed that when adjusted for age, sex, and aid program, total costs for Hispanic patients decreased as the length of care increased, in contrast to other ethnic groups. The interaction between ethnicity and treatment progression measured by quarter was significant (P < 0.0001), but ethnicity as a main effect was not (P = 0.091). This suggests that differences in total costs are small initially, but as the followup period extends, Hispanic patients experience lower total costs as compared with other ethnic groups.

Conclusion

These California Medicaid program data reinforce the importance of investigating treatment differences in ethnic groups with SLE.
Pregnancy, cytokines, and disease activity in systemic lupus erythematosus
Authors: Doria Andrea , Ghirardello Anna , Iaccarino Luca , Zampieri Sandra , Punzi Leonardo , Tarricone Elena , Ruffatti Amelia , Sulli Alberto , Sarzi‐Puttini Pier Carlo , Gambari Pier Franca , Cutolo Maurizio
Published: December 2004

Objective

To evaluate levels of selected cytokines and soluble receptors involved in the humoral immune response during pregnancy in systemic lupus erythematosus (SLE) patients.

Methods

Seventeen consecutive SLE patients and 8 matched healthy controls were prospectively studied during pregnancy. Sera were obtained within the last 3 months prior to pregnancy; at 9, 17, and 29 weeks of pregnancy; and at 1 month after delivery. Serum levels of interleukin‐10 (IL‐10), interleukin‐6 (IL‐6), and soluble tumor necrosis factor receptors p55 (sTNFR I) and p75 (sTNFR II) were evaluated. SLE activity was measured by the European Consensus Lupus Activity Measurement score modified for pregnancy.

Results

IL‐10 serum levels were found to be higher (P < 0.0001) in patients than in controls before conception, and still higher (P < 0.0001) in SLE patients during gestation, without intertrimester changes. In SLE patients, IL‐6 serum levels did not increase in the third trimester of pregnancy, as was observed in controls (P = 0.011). No significant differences between SLE patients and controls were found in either sTNFR I or II levels or profiles before and during pregnancy. IL‐10 and sTNFR I levels were significantly higher during pregnancy and postpartum in SLE patients with active disease (P = 0.03 and P = 0.01, respectively).

Conclusion

The levels of some cytokines involved in the humoral immune response seem to be modified in the peripheral circulation of pregnant SLE patients. The most relevant modifications are the lower than expected increase of IL‐6 in the third trimester of gestation and persistently high levels of IL‐10 during pregnancy.
Content comparison of occupation‐based instruments in adult rheumatology and musculoskeletal rehabilitation based on the International Classification of Functioning, Disability and Health
Authors: Stamm Tanja A. , Cieza Alarcos , Machold Klaus P. , Smolen Josef S. , Stucki Gerold
Published: December 2004

Objective

To compare the content of clinical, occupation‐based instruments that are used in adult rheumatology and musculoskeletal rehabilitation in occupational therapy based on the International Classification of Functioning, Disability and Health (ICF).

Methods

Clinical instruments of occupational performance and occupation in adult rehabilitation and rheumatology were identified in a literature search. All items of these instruments were linked to the ICF categories according to 10 linking rules. On the basis of the linking, the content of these instruments was compared and the relationship between the capacity and performance component explored.

Results

The following 7 instruments were identified: the Canadian Occupational Performance Measure, the Assessment of Motor and Process Skills, the Sequential Occupational Dexterity Assessment, the Jebson Taylor Hand Function Test, the Moberg Picking Up Test, the Button Test, and the Functional Dexterity Test. The items of the 7 instruments were linked to 53 different ICF categories. Five items could not be linked to the ICF. The areas covered by the 7 occupation‐based instruments differ importantly: The main focus of all 7 instruments is on the ICF componentactivities and participation.Body functionsare covered by 2 instruments. Two instruments were linked to 1 single ICF category only.

Conclusion

Clinicians and researchers who need to select an occupation‐based instrument must be aware of the areas that are covered by this instrument and the potential areas that are not covered at all.
Practice, training, and assessment among experts performing musculoskeletal ultrasonography: Toward the development of an international consensus of educational standards for ultrasonography for rheumatologists
Authors: Brown Andrew K. , O'Connor Philip J. , Wakefield Richard J. , Roberts Trudie E. , Karim Zunaid , Emery Paul
Published: December 2004

Objective

To evaluate the training and practice of specialist practitioners in musculoskeletal ultrasonography (MUS) with the aim of developing an expert‐derived consensus of educational standards for rheumatologists performing MUS.

Methods

A panel of worldwide experts in MUS was identified by literature review, consultation with members of training committees, and peer recommendation. Using a postal questionnaire, information was obtained about personal experience, current practice, training regimen, and participation in competency assessment.

Results

International experts in MUS were identified (57 in total: 37 radiologists, 20 rheumatologists). Response rate was 70%. Radiologists had been performing MUS for longer than rheumatologists. Both rheumatologists and radiologists conducted the same number of MUS sessions per week, although radiologists examined more patients. More radiologists performed MUS for muscle and ligament injury, nerve lesions, soft tissue masses, and of the groin (P < 0.01). The number of training hours was similar. Approaches to training varied, although attending a training course and scanning with an expert was more common among rheumatologists (P < 0.001). More than two‐thirds of the group had not undergone any form of competency assessment.

Conclusion

This study highlights differences in training and practice between individual expert ultrasonographers and between specialty backgrounds. In particular, there appears to be no formal training regimen and competency assessment is uncommon. The establishment of a core set of internationally applicable educational standards for MUS training for rheumatologists is required.
In Vitro inhibitory effects of non‐steroidal antiinflammatory drugs on UDP‐glucuronosyltransferase 1A1‐catalysed estradiol 3β‐glucuronidation in human liver microsomes
Authors: Mano Yuji , Usui Takashi , Kamimura Hidetaka
Published: December 2004

The inhibitory potencies of non‐steroidal antiinflammatory drugs (NSAID) on UDP‐glucuronosyltransferase (UGT) 1A1‐catalysed estradiol 3β‐glucuronidation (E3G) were investigated in human liver microsomes (HLM). Inhibitory effects of the following seven NSAID were investigated: acetaminophen, diclofenac, diflunisal, indomethacin, ketoprofen, naproxen and niflumic acid. Niflumic acid had the most potent inhibitory effect on E3G with an IC50 value of 22.2 µM in HLM. The IC50 values of diclofenac, diflunisal, indomethacin for E3G were 60.9, 37.8 and 51.5 µM, respectively, while acetaminophen, ketoprofen and naproxen showed less potent inhibition. Diclofenac inhibited E3G non‐competitively with a Ki value of 112 µM in HLM. The IC50 value of diclofenac for 4‐methylumbelliferone glucuronidation in recombinant human UGT1A1 was 57.5 µM, similar to that obtained for E3G using HLM.

In conclusion, niflumic acid had the most potent inhibitory effects on UGT1A1‐catalysed E3G in HLM among seven NSAID investigated. Copyright © 2004 John Wiley & Sons, Ltd.
De novo renal cell carcinoma of native kidney in renal transplant recipients
Authors: Neuzillet Yann , Lay Franck , Luccioni Aline , Daniel Laurent , Berland Yvon , Coulange Christian , Lechevallier Eric
Published: December 2004

BACKGROUND

The 10‐year risk of developing a solid malignancy is 20% for kidney transplant recipients. The goal of the current study was to investigate the epidemiology and the diagnostic and prognostic parameters associated with de novo malignancies of the native kidney among transplant recipients at the authors' institution (Department of Urology and Renal Transplantation, Hôpital Salvator, Marseille, France).

METHODS

The authors reexamined the follow‐up of 933 consecutive transplant recipients at their institution between 1987 and 2003. Immunossupressive therapy was not modified in the event of malignant disease, nor was systematic radiologic monitoring of native kidneys performed. All de novo malignancies of the native kidney were included in the current analysis.

RESULTS

Among the 933 patients examined, a combined total of 12 malignancies of the native kidney were diagnosed in 11 individuals. For these 11 individuals, the average ages at transplantation and diagnosis were 42.5 and 49.1 years, respectively. Ten malignancies were discovered fortuitously, whereas two were symptomatic. Among the 10 renal echographies performed, there was 1 false‐negative result. Tomodensitometry was performed in 11 cases and yielded no false‐negative results. The average tumor size was 37 mm. Nephrectomy was performed in 10 cases, and biopsy was performed in 1. Among the 12 kidney malignancies encountered in the current study, there were 7 conventional cell carcinomas, 3 basophilic papillary carcinomas, and 2 chromophobic renal cell carcinomas. Half of all tumors were Furhman Grade 3 lesions, and pT1aN0M0 tumors (2003 TNM staging system) also accounted for half of all malignancies in the current cohort. Two affected transplant recipients died (one due to disease), and the remaining nine are alive without recurrence and with normal renal functioning (median follow‐up, 39 months).

CONCLUSIONS

There appears to be an increased risk of malignancy of the native kidney in renal transplant recipients, with high‐grade and papillary tumors being particularly common. Consequently, systematic radiologic follow‐up of native kidneys must be performed for individuals who undergo kidney transplantation. Cancer 2005. © 2004 American Cancer Society.
Prediction of survival in patients with metastases in the spinal column
Authors: van der Linden Yvette M. , Dijkstra Sander P. D. S. , Vonk Ernest J. A. , Marijnen Corrie A. M. , Leer Jan Willem H. ,   for The Dutch Bone Metastasis Study Group
Published: December 2004

BACKGROUND

Adequate prediction of survival is important in deciding on treatment for patients with symptomatic spinal metastases. The authors reviewed 342 patients with painful spinal metastases without neurologic impairment who were treated conservatively within a large, prospectively randomized radiotherapy trial. Response to radiotherapy and prognostic factors for survival were studied.

METHODS

The data base of the Dutch Bone Metastasis Study was used. Response to treatment and prognostic factors for overall survival (OS) were studied using a Cox regression model. A scoring system was developed to predict OS.

RESULTS

Responses were noted in 73% of patients. In 3% of patients, spinal cord compression was reported a mean of 3.5 months after randomization. The median OS was 7 months, and significant predictors for survival were Karnofsky performance score, primary tumor (multivariate analysis; both P < 0.001), and the absence of visceral metastases (multivariate analysis; P = 0.02). A scoring system based on these predictors was developed, and 34% of patients were in Group A (median OS = 3.0 months), 48% of patients were in Group B (median OS = 9.0 months), and 18% of patients were in Group C (median OS = 18.7 months). Group C was comprised of patients with breast carcinoma, a good performance, and no visceral metastases.

CONCLUSIONS

Most patients with spinal metastases have a limited life expectancy and should be treated with caution regarding surgical procedures. Radiotherapy is a safe and effective, noninvasive treatment modality for pain. The new scoring system will enable physicians to select patients who may survive long enough to benefit from more radical treatment. Cancer 2005. © 2004 American Cancer Society.
Characterization of linkage disequilibrium structure, mutation history, and tagging SNPs, and their use in association analyses: ELAC2 and familial early‐onset prostate cancer
Authors: Camp Nicola J. , Swensen Jeff , Horne Benjamin D. , Farnham James M. , Thomas Alun , Cannon‐Albright Lisa A. , Tavtigian Sean V.
Published: December 2004

In association analyses, it is critical that informative single‐nucleotide polymorphisms (SNPs) be selected for study and utilized appropriately. We sequenced 38 kb, including exons of ELAC2, promoter region and conserved upstream intergenic sequences. A comprehensive characterization of linkage disequilibrium (LD) structure and mutation history was performed using our principal components analysis (PCA) method and a phylogenetic analysis. We identified a complex pattern of LD structure consistent with the occurrence of both recombination and mutation events within ELAC2. Four overlapping and noncontiguous LD groups were defined. Eight tagging SNPs (tSNPs) were identified, accounting for over 90% of the genetic variation of the 19 total variants. We tested associations between familial early‐onset prostate cancer (PRCA) and each variant independently and in haplotypes. We performed these tests using all 19 variants and the 8 tSNPs; the results using tSNP haplotypes accurately represent the association evidence for the full haplotypes. We observed increased evidence for association when SNPs were analyzed in haplotypes. The phylogenetic analysis indicated three haplotypes, clustered farthest from the root‐node, all of which were found more often in cases than controls. These three haplotypes together showed the best evidence of association with familial, early‐onset PRCA (P=0.0024; odds ratio=2.23; 95% CI, 1.33–3.74), indicating possible allelic heterogeneity. Our results suggest that 8 tSNPs are required to comprehensively assess associations in ELAC2, and that haplotypes should be considered for analysis, and that a knowledge of mutation history may be helpful in parsing allelic heterogeneity and suggesting combinations of haplotypes to be tested. Genet. Epidemiol. © 2004 Wiley‐Liss, Inc.
The utilization of training program evaluation in corporate universities
Authors: Bober Christopher F. , Bartlett Kenneth R.
Published: December 2004

This study examined the use of training program evaluation results in corporate universities. Specifically, the study attempted to determine which organizational members use evaluation data, and for what purposes, and identify the factors that are related to the use of evaluation results. The study was designed to test the appropriateness of the Cousins and Leithwood (1986) meta‐analytic conceptual framework for evaluation utilization. A case study approach was used to collect qualitative data at four corporate universities in the United States. On‐site interviews with key personnel and in‐depth document review of applicable training program evaluation information were conducted. Results showed a high degree of consensus on evaluation uses and users. Seven of the twelve factors from the Cousins and Leithwood framework were found at all four sites to influence utilization. The findings indicate that factors identified as being influential to evaluation utilization related to implementation dominated over factors related to uses for decision/policy setting.
An examination of work‐environment support factors affecting transfer of supervisory skills training to the workplace
Authors: Cromwell Susan E. , Kolb Judith A.
Published: December 2004

Organizations invest a significant amount of time and money on management and supervisory training programs. The intent of this study was to examine the relationship between four specific work‐environment factors (organization support, supervisor support, peer support, and participation in a peer support network) and transfer of training at one‐month, six‐month, and one‐year points following supervisory skills training. Quantitative and qualitative data were collected from both trainees and their direct supervisors. ANOVA results of aggregate data showed that trainees who reported receiving high levels of organization, supervisor, and peer support, and who also participated in a peer support network, reported higher levels of transfer of knowledge and skills. When data were segregated and examined according to length of time since trainees had completed training, findings were still significant for organization, supervisor, and peer support but only at the one‐year point, not at one month or six months. Participation in a peer support network was not significant at any of the three points of time. In short‐answer responses, trainees indicated that lack of time and lack of management support and buy‐in were significant barriers to transfer. T‐test results indicated that trainees and their supervisors did not differ in their perceptions of level of transfer of skills or amount of organizational or direct supervisor support received by the trainees.
The influences of the Southern and North Atlantic Oscillations on climatic surface variables in Turkey
Authors: Karabörk M. Çaǧatay , Kahya Ercan , Karaca Mehmet
Published: December 2004

In this study, Turkish climatic variables (precipitation, stream flow and maximum and minimum temperatures) were first analysed in association with both the Southern Oscillation (SO) and the North Atlantic Oscillation (NAO). The relationships between Turkish maximum and minimum monthly temperatures and the extreme phases of the SO (El Niño and La Niña events) were examined. The results of this analysis showed that relationships between Turkish monthly maximum temperatures and El Niño and La Niña contain some complexity still to be identified, because both events produce a signal indicating a correspondence with cold anomalies in the aggregate composites. A relationship between turkish minimum temperatures and El Niño was detected in western Anatolia, whereas there was no significant and consistent signal associated with La Niña. Moreover a series of cross‐correlation analyses was carried out to demonstrate the teleconnections between the climatic variables and both the NAO and SO. The NAO during winter was found to influence precipitation and stream‐flow patterns. In contrast temperature patterns appeared to be less sensitive to the NAO. Furthermore, lag‐correlation results indicated a prediction potential for both precipitation and stream‐flow variables in connection with the NAO. Simultaneous and time‐lag correlations between the climatic variables and the SO index, in general, indicated weaker relationships in comparison with those for the NAO. These analyses also showed that the influences of the SO on Turkish temperature data are negligible. The outcomes were presented in conjunction with an explanation regarding physical mechanisms behind the implied teleconnections. Copyright © 2004 John Wiley & Sons, Ltd.
Evapotranspiration from a wet temperate grassland and its sensitivity to microenvironmental variables
Authors: Li S.‐G. , Lai C.‐T. , Lee G. , Shimoda S. , Yokoyama T. , Higuchi A. , Oikawa T.
Published: December 2004

The eddy covariance and energy balance method was employed to determine evapotranspiration (LE) over a wet temperate C3–C4 co‐existing grassland in Japan. After sensible heat flux (H) was estimated via the eddy covariance technique, LE was calculated as the residual of the energy budget with calibration against the direct measurements of LE by a lysimeter. Daily mean LE varied from 0·8 to 10·5 MJ d−1, with a peak at 16·5 MJ d−1 in late July to early August. Day‐to‐day and seasonal variability in LE was affected appreciably by net radiation (Rn), atmospheric vapour pressure deficit (VPD), canopy surface conductance (gc) and leaf area index (LAI). Before the canopy closure, LE responded to LAI in a linear manner. However, LE decreased with increasing LAI later in summer. Daytime variation in the decoupling coefficient (Ω) demonstrates that the canopy decoupled from the atmosphere in the morning and LE was primarily driven by the available energy, while in the afternoon the canopy partially coupled to the atmosphere so that LE was sensitive to VPD and gc. Throughout the whole measurement period, Ω was generally larger than 0·5, suggesting that the available energy contributes more to LE than VPD. Copyright © 2004 John Wiley & Sons, Ltd.
Robust inference concerning recent trends in US environmental quality
Authors: Maasoumi Esfandiar , Millimet Daniel L.
Published: December 2004

Understanding trends in environmental quality is important for individuals and policymakers. Typically, trends in environmental quality are determined solely through comparisons of unconditional or conditional mean pollution levels. However, reaching unambiguous conclusions on the basis of only the first moment of the (unconditional or conditional) distribution is problematic since it ignores what is occurring in different regions of the distribution. Even relying on indices that incorporate both mean and variance is suspect to the extent that relative rankings are not typically robust to index choice. Addressing these concerns, we adapt recent developments in the stochastic dominance literature to test for unambiguous relations between current and past distributions of toxic releases. Using EPA data from 1988–1999, we find statistically significant evidence that the unconditional 1999 distributions of air, land, underground and total toxic releases dominate in a first‐degree sense their respective 1988 distributions. While some of this improvement is explained by economic growth, pollution net‐of‐income improved over the sample period as well. Finally, we document robust differences in the distribution of pollution across regions in the US. Copyright © 2004 John Wiley & Sons, Ltd.
Dvl2 silencing in postdevelopmental cells results in aberrant cell membrane activity and actin disorganization
Authors: Wechezak Arlene R. , Coan Daniel E.
Published: December 2004

The upstream events by which endothelial cells perceive the necessity for migration and how this signal results in coordinated movement is unknown. The synchrony underlying these events shares parallels to events occurring during the movement of tissues in embryogenesis. While Wnt signaling is an important pathway in development, components of the cascade exist in postdevelopment endothelial cells. The objective of this study was to determine whether Dishevelled, a key modulation protein in canonical and PCP‐CE Wnt signaling was present in endothelium and its potential function. Western blots of cell lysates and immunolabeling studies confirmed that Dishevelled 2 (Dvl2) is an abundant phosphoprotein in endothelial cells. Dvl2 was localized within the cytoplasm of cells as either F‐actin‐free or F‐actin‐associated. The disappearance of F‐actin‐free Dvl2 in vesicle‐like organelles and targeting of actin filaments correlated with a loss in cell motility. Gene silencing of Dishevelled by siRNA duplexes resulted in cells with aberrant membrane activity and an inability to extend lamellipodia. Underlying these abnormalities was a disorganization of the actin filament system, including loss of actin‐rich densities, indistinct stress fibers and an accompanying increase in diffuse and aggregate cytoplasmic actin. This study represents the first documentation of Dvl2 in postdevelopmental endothelial cells and its possible role in cell migration via manipulation of actin filament bundles. © 2004 Wiley‐Liss, Inc.
Volunteer and coordinator perspectives on managing women volunteers
Authors: Leonard Rosemary , Onyx Jenny , Hayward‐Brown Helen
Published: December 2004

Recent changes in Australia, such as the new public management and national competition policy, have affected the way that human services are provided and have complicated the role of volunteer coordinators. However, because volunteers are free to choose their level of contribution, it is the volunteers' perspective that is the ultimate yardstick against which their coordination is assessed. The aim of the research examined here was a deeper understanding of women volunteers' and their coordinators' views of their work. The research was conducted within a qualitative paradigm, employing individual and focus group interviews. The analysis identified eight areas of concern for volunteers around their management. The analysis of the coordinators' interviews revealed three coordination styles—horizontal, nurturing, and managerial—of which the managerial was most in conflict with the volunteers' perspective.