bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiological Condition of Urban Groundwater in the Vicinity of Leaky Sewer Systems
Authors: Paul Miriam , Wolf Leif , Fund Katharina , Held Inka , Winter Josef , Eiswirth† Matthias , Gallert Claudia , Hötzl Heinz
Published: December 2004

The possible deterioration of the microbiological quality of groundwater due to leaky sewer systems was investigated in a medium‐sized city (Rastatt) in SW‐Germany. Specially constructed focus observation wells drilled close to leaky sewers have been compared with the background observation wells in urban and rural areas.

The sampling was performed in March (shallow depth of groundwater) and in July and October (deep groundwater table). It included the measurement of ammonium ions, temperature, electric conductivity, oxygen, and the depth of the groundwater table. Coliforms, Escherichia coli, and enterococci were enumerated as indicator organisms for wastewater contamination. In addition, the total number of colony forming units was determined.

Bacterial counts of coliforms and E. coli generally increased during the course of the investigation (March to October). This may have been caused either by a slightly increased groundwater temperature (higher activity rates) or by a higher proportion of sewage in the urban groundwater system as a result of the dry season (summer). The contamination with faecal indicator bacteria was greater adjacent to leakage locations. In addition, elevated concentrations of ammonium ions were observed at these areas. The results provide evidence that leaky sewer systems elevate faecal indicator concentrations in groundwater with associated potential health risk where such waters are used for potable water supply.
Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti–cyclic citrullinated peptide antibody
Authors: Mikuls T. R. , O'Dell J. R. , Stoner J. A. , Parrish L. A. , Arend W. P. , Norris J. M. , Holers V. M.
Published: December 2004

Objective

To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti‐CCP) antibody levels among patients with rheumatoid arthritis (RA).

Methods

The study sample included 66 RA patients who completed double‐blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti‐CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels.

Results

Patients had a mean ± SD age of 49.9 ± 12.0 years and were predominantly female (n = 51; 77%). The mean ± SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 ± 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a ≥25% reduction in the anti‐CCP antibody level during the course of treatment, and 35 patients (55%) had a ≥25% reduction in RF. After adjustment for the baseline anti‐CCP antibody level, only a shorter disease duration (≤12 months) was significantly associated with a decline in the level of anti‐CCP antibody (OR 3.0, 95% CI 1.0–8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2–10.4).

Conclusion

Shorter disease duration predicts greater declines in anti‐CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti‐CCP antibody level.
Efficacy and tolerability of a selective α2C‐adrenergic receptor blocker in recovery from cold‐induced vasospasm in scleroderma patients: A single‐center, double‐blind, placebo‐controlled, randomized crossover study
Authors: Wise Robert A. , Wigley Fredrick M. , White Barbara , Leatherman Gwen , Zhong Jianhua , Krasa Holly , Kambayashi Jun‐ichi , Orlandi Cesare , Czerwiec Frank S.
Published: December 2004

Objective

OPC‐28326 is a selective α‐adrenergic antagonist with preferential binding to the α2C‐adrenergic receptor (α2C‐AR) subtype. This study observed the effect of OPC‐28326 on skin temperature and digital blood flow following an acute cold challenge in patients with Raynaud's phenomenon secondary to scleroderma.

Methods

The study was designed as a single‐center, double‐blind, placebo‐controlled, randomized, 3‐period crossover study of OPC‐28326 (oral doses of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to recover 50% and 70% of the fall (induced by cold challenge) in baseline digital skin temperature.

Results

Twelve of 13 enrolled patients completed the study. The mean time to achieve 50% and 70% recovery of the change in prechallenge digital skin temperature was shorter after the OPC‐28326 40‐mg dose than after placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to be shorter in the 10 mg OPC‐28326 group as well, but the difference versus placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P = 0.65]; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total digital blood flow tended to be lower prior to the cold challenge and after administration of 40 mg OPC‐28326, as compared with that after placebo, but the difference was not significant. Symptoms that were potentially drug‐related were reported more frequently with 40 mg OPC‐28326 than with 10 mg OPC‐28326 or with placebo, but none were serious or sustained.

Conclusion

OPC‐28326 at doses of 10 mg and 40 mg was well tolerated during this study. The shorter time to skin temperature recovery after 40 mg OPC‐28326 suggests that selective α2C‐AR blockade improves digital skin perfusion during recovery from cooling in patients with Raynaud's phenomenon secondary to scleroderma.
A shift in the balance of inhibitory and activating Fcγ receptors on monocytes toward the inhibitory Fcγ receptor IIb is associated with prevention of monocyte activation in rheumatoid arthritis
Authors: Wijngaarden Siska , van de Winkel Jan G. J. , Jacobs Kim M. G. , Bijlsma Johannes W. J. , Lafeber Floris P. J. G. , van Roon Joel A. G.
Published: December 2004

Objective

To assess surface expression of the inhibitory receptor for IgG (Fcγ receptor IIb [FcγRIIb]) in relation to activating FcγR on monocyte/macrophages from patients with rheumatoid arthritis (RA) and healthy controls and to study the influence of proinflammatory and antiinflammatory cytokines on the balance of inhibitory and activating FcγR.

Methods

Using a combination of genotyping and phenotyping, surface expression of FcγRIIb on monocytes from healthy control subjects and RA patients was demonstrated. Expression of FcγR on CD14+ monocytes was assessed by flow cytometry. Regulation of inhibitory and activating FcγR on monocytes by proinflammatory (interferon‐γ [IFNγ], tumor necrosis factor α [TNFα]) and antiinflammatory (interleukin‐4 [IL‐4], IL‐10) cytokines was studied. A functional change in cytokine‐modulated monocytes was assessed in secondary cultures by their ability to produce TNFα upon FcγR crosslinking by IgG.

Results

Monocytes from healthy controls and RA patients expressed FcγRIIb at similar levels, in contrast to the higher levels of activating FcγRI and FcγRIIa in RA patients. The regulation of FcγR expression was comparable for patients and controls. IFNγ selectively up‐regulated FcγRI. TNFα down‐regulated expression of FcγRIIb and the activating FcγR, whereas IL‐10 up‐regulated expression of monocytic FcγRIIb and all activating FcγR. Increased or sustained levels of activating over inhibitory FcγR induced by IFNγ, TNFα, and IL‐10 alone were associated with enhanced IgG‐triggered TNFα production. In contrast, IL‐4 and, more specifically, IL‐4 plus IL‐10 altered the FcγR balance in favor of FcγRIIb and completely prevented IgG‐triggered TNFα production.

Conclusion

The altered balance of FcγR in favor of activating receptors in RA may contribute to increased activation of monocyte/macrophages. A change in the FcγR balance toward the inhibitory FcγRIIb may offer a novel treatment strategy for preventing the pleiotropic activity of FcγR‐triggered macrophages.
Assessment of the efficacy of different statins in murine collagen‐induced arthritis
Authors: Palmer Gaby , Chobaz Véronique , Talabot‐Ayer Dominique , Taylor Sophia , So Alexander , Gabay Cem , Busso Nathalie
Published: December 2004

Objective

Hydroxymethylglutaryl‐coenzyme A reductase inhibitors (statins) are widely used lipid‐lowering agents. In addition to their well‐known effect on cholesterol levels, statins have been reported to display antiinflammatory activities both in vitro and in vivo. In this context, in vivo prophylactic and therapeutic effects of simvastatin were recently demonstrated in mouse collagen‐induced arthritis, a well‐described experimental model for human rheumatoid arthritis (RA). The aim of this study was to further investigate in vivo effects of 3 different statins, atorvastatin, rosuvastatin, and simvastatin, using the same experimental model.

Methods

Different doses and routes of administration were used for the various statins in an attempt to elicit antiarthritic activity in preventive and curative treatment protocols.

Results

Atorvastatin and rosuvastatin had no in vivo efficacy, as indicated by clinical, histologic (synovial hyperplasia, exudate, and cartilage damage), immunologic (anti–type II collagen IgG production), and biochemical (interleukin‐6, serum amyloid A, and glucocorticoid production) parameters of inflammation and autoimmunity. The previously described beneficial effects of administration of intraperitoneal simvastatin were reproduced in our experiments, but could be accounted for by very severe side effects of the treatment, leading to increased glucocorticoid levels.

Conclusion

This work shows that different statins have no effect in a murine model of arthritis, an unexpected observation given the previously described therapeutic effect of statins in immune‐mediated inflammatory diseases. It is still unclear whether statins will have benefit in the treatment of RA.
Effect of intermittent administration of human parathyroid hormone on bone mineral density and arthritis in rats with collagen‐induced arthritis
Authors: Fukata Satoru , Hagino Hiroshi , Okano Toru , Yamane Itsuro , Kameyama Yasuhiro , Teshima Ryota
Published: December 2004

Objective

To investigate the effect of intermittent administration of human parathyroid hormone (PTH) on bone mineral density (BMD) and arthritis in rats with collagen‐induced arthritis (CIA).

Methods

Seven‐month‐old female Sprague‐Dawley rats were divided into 4 groups: rats without CIA (control), rats with CIA treated with vehicle, rats with CIA treated with PTH for 4 weeks, and rats with CIA treated with PTH for 6 weeks. PTH (20 μg/kg) was injected subcutaneously 3 times per week. BMD in the proximal metaphysis and the diaphysis of the tibia was measured by peripheral quantitative computed tomography every 2 weeks until week 8. Eight weeks after initial sensitization, the animals were killed, and the BMD and mechanical properties of excised limbs were evaluated. Histomorphometric analysis of tibiae and histologic evaluation of arthritis were also performed.

Results

In the PTH‐treated rats with CIA, the incidence and severity of arthritis were macroscopically and histologically similar to the findings in the vehicle‐treated rats with CIA. The decrease of BMD caused by CIA was suppressed by treatment with human PTH, in a manner that was dependent on the duration of administration. In the histomorphometric analysis, bone formation parameters were higher and bone resorption parameters were lower in the PTH‐treated arthritic rats compared with vehicle‐treated arthritic rats. Mechanical properties were also maintained in the PTH‐treated rats.

Conclusion

Our findings indicate that, in an animal model of arthritis, intermittent PTH administration activates bone formation, resulting in increased BMD and preventing deterioration of mechanical properties. However, PTH has no effect on the arthritis itself.
Enhanced generation of endothelial cells from CD34+ cells of the bone marrow in rheumatoid arthritis: Possible role in synovial neovascularization
Authors: Hirohata Shunsei , Yanagida Tamiko , Nampei Akihide , Kunugiza Yasuo , Hashimoto Hideo , Tomita Tetsuya , Yoshikawa Hideki , Ochi Takahiro
Published: December 2004

Objective

To examine the capacity of bone marrow CD34+ cells to generate endothelial cells, in order to assess the role of bone marrow in neovascularization in the synovium of rheumatoid arthritis (RA).

Methods

CD34+ cells purified from the bone marrow of 13 patients with active RA and 9 control subjects (7 osteoarthritis [OA] patients and 2 healthy individuals) were cultured in the presence of stem cell factor (10 ng/ml) and granulocyte–macrophage colony‐stimulating factor (1 ng/ml). After 18 days of incubation, the generation of endothelial cells was assessed by flow cytometry. The generation of endothelial cells was compared with the degree of vascularization in the synovial tissues and with the microvessel densities in the synovium, as determined by microscopy. The expression of vascular endothelial growth factor receptor 2/kinase insert domain receptor (KDR) messenger RNA (mRNA) in CD34+ cells was examined by quantitative reverse transcription–polymerase chain reaction.

Results

The generation of CD14+ cells from bone marrow–derived CD34+ cells from RA patients was comparable to that from control subjects. However, the generation of von Willebrand factor (vWF)–positive cells and CD31+/vWF+ cells from RA bone marrow–derived CD34+ cells was significantly higher than that from control subjects (P = 0.004 and P = 0.030, respectively). The generation of vWF+ cells from bone marrow CD34+ cells correlated significantly with the microvessel densities in the synovial tissues (r = 0.569, P = 0.021). Finally, RA bone marrow CD34+ cells expressed KDR mRNA at higher levels than OA bone marrow CD34+ cells.

Conclusion

These results indicate that RA bone marrow CD34+ cells have enhanced capacities to differentiate into endothelial cells in relation to synovial vascularization. The data therefore suggest that bone marrow CD34+ cells might contribute to synovial neovascularization by supplying endothelial precursor cells and, thus, play an important role in the pathogenesis of RA.
Childhood‐onset osteoarthritis, tall stature, and sensorineural hearing loss associated with Arg75‐Cys mutation in procollagen type II gene (COL2A1)
Authors: Löppönen Tuija , Körkkö Jarmo , Lundan Tuija , Seppänen Ulpu , Ignatius Jaakko , Kääriäinen Helena
Published: December 2004

Objective

To define the clinical, radiologic, and molecular genetic characteristics of a family with early progressive osteoarthritis mimicking childhood rheumatoid arthritis, Scheuermann‐like changes of the spine, tall stature, short 3 and 4 metatarsals, and moderate sensorineural hearing loss.

Methods

We describe a 22‐year‐old woman and her 54‐year‐old mother with early progressive osteoarthritis mimicking childhood rheumatoid arthritis. The index case, her mother, and 3 other family members underwent a physical examination, anthropometric measurements, and radiologic studies. Their DNA was sequenced for the procollagen type II (COL2A1) gene.

Results

Mild scoliosis was noticed in the proband at the age of 6 years, and at the age of 7 years large Schmorl's nodes were found in the vertebrae L1‐2. At the age of 11 years, changes resembling Scheuermann's disease were seen, mostly in the thoracic vertebrae. At the same age, she began to have arthralgia in the weight‐bearing joints and osteoarthritis progressed fast, necessitating a hip prosthesis at the age of 18 years. The proband and her mother had bilateral sensorineural hearing loss of moderate degree. Both mother and daughter had an Arg75‐Cys mutation in the COL2A1 gene.

Conclusion

This family is the fourth example of the Arg75‐Cys mutation in the COL2A1 gene, which appears to lead to a clearly recognizable phenotype. The finding suggests that sensorineural hearing loss may be a part of this syndrome.
Beer, liquor, and wine consumption and serum uric acid level: The Third National Health and Nutrition Examination Survey
Authors: Choi Hyon K. , Curhan Gary
Published: December 2004

Objective

To evaluate the relationship between intakes of beer, liquor, and wine and serum uric acid levels in a nationally representative sample of men and women.

Methods

Using data from 14,809 participants (6,932 men and 7,877 women) age ≥20 years in The Third National Health and Nutrition Examination Survey (1988–1994), we examined the relationship between intakes of beer, liquor, and wine and serum uric acid levels. Alcohol intake was assessed by a food frequency questionnaire.

Results

Serum uric acid levels increased with increasing beer or liquor intake but not with increasing wine intake. After adjusting for age, the difference in serum uric acid levels as compared with no intake increased with increasing beer or liquor intake (P values for trend < 0.001), but the association was inverse with increasing wine intake (P for trend < 0.001). After adjusting mutually for these alcoholic beverages and for other risk factors for hyperuricemia, including dietary risk factors, the associations were attenuated but remained significant for beer or liquor (multivariate difference per serving per day 0.46 mg/dl [95% confidence interval {95% CI} 0.32, 0.60] and 0.29 mg/dl [95% CI 0.14, 0.45], respectively; both P values for trend <0.01), but not for wine (0.04 mg/dl [95% CI −0.20, 0.11]; P for trend = 0.6).

Conclusion

These data suggest that the effect of individual alcoholic beverages on serum uric acid levels varies substantially: beer confers a larger increase than liquor, whereas moderate wine drinking does not increase serum uric acid levels.
Managing arthritis and employment: Making arthritis‐related work changes as a means of adaptation
Authors: Gignac Monique A. M. , Badley Elizabeth M. , Lacaille Diane , Cott Cheryl C. , Adam Paul , Anis Aslam H.
Published: December 2004

Objective

To understand arthritis‐related workplace changes, including occasional work loss and changes to the type and hours of work, and the factors associated with them using theories of adaptation and behavior change as a framework.

Methods

Participants were 492 employed individuals with rheumatoid arthritis or osteoarthritis. They completed an interview‐administered, structured questionnaire assessing demographic, workplace, and psychosocial variables, as well as such work transitions as changes to the hours, type, and nature of work. Hypotheses were examined using multiple linear regression.

Results

Seventy percent of respondents made at least 1 work change. Younger participants and those with greater workplace activity limitations reported more changes. Work changes were associated with greater depression. A hypothesized 3‐way interaction among people's perceptions of their capacity, their future job expectations, and whether they had told their employer about their arthritis was significant.

Conclusion

This study extends arthritis employment research by examining a range of work changes. It highlights the dynamic interplay among arthritis, workplace, and psychosocial variables to understand adaptation to arthritis disability.
Cardiac risk factor awareness and management in patients with systemic lupus erythematosus
Authors: Costenbader Karen H. , Wright Elizabeth , Liang Matthew H. , Karlson Elizabeth W.
Published: December 2004

Objective

To assess awareness and management of traditional cardiac risk factors (CRFs) in patients with systemic lupus erythematosus (SLE) and physicians.

Methods

SLE patients (n = 110) completed a questionnaire concerning CRFs. Medical records were reviewed blinded to questionnaire results for the presence and management of 6 CRFs: hypertension, hypercholesterolemia, smoking, obesity, diabetes mellitus, and physical inactivity.

Results

Subjects were predominantly female (97%), mean (±SD) age was 43.4 years (±11.8), mean SLE duration was 15.3 years (±7.2), and 51% had ≥2 CRFs by self report. Twenty‐three percent had never had their cholesterol levels checked. Hypercholesterolemia was more frequently documented in the medical records than reported by the patient (33% versus 24%). Physical inactivity was more frequently self reported than documented (59% versus 23%). Rheumatologists and patients had low interrater reliability for the presence of hypercholesterolemia (κ = 0.26) and physical inactivity (κ = –0.02). More than half (58%) of CRFs were treated, and 21% of subjects with elevated cholesterol received a medication.

Conclusion

Recognition, recording, and management of CRFs falls short given the significance of the problem.
Subject retention and adherence in a randomized placebo‐controlled trial of a disease‐modifying osteoarthritis drug
Authors: Mazzuca Steven A. , Brandt Kenneth D. , Katz Barry P. , Lane Kathleen A. , Bradley John D. , Heck Louis W. , Hugenberg Steven T. , Manzi Susan , Moreland Larry W. , Oddis Chester V. , Schnitzer Thomas J. , Sharma Leena , Wolfe Frederick , Yocum David E.
Published: December 2004

Objective

To describe the methods by which remarkable levels of subject retention and adherence were achieved in a 30‐month multicenter randomized placebo‐controlled trial (RCT) of a disease‐modifying osteoarthritis drug (DMOAD).

Methods

Subjects were obese 45–64‐year‐old women with unilateral knee osteoarthritis. Before randomization, each volunteer completed a 4‐week “faintness‐of‐heart” (FOH) test, during which she was required to demonstrate reliable appointment keeping and ≥80% adherence to the dosing regimen. Subjects who passed the FOH test were randomized to treatment with doxycycline or placebo for 30 months. The double‐blind phase entailed 15 bimonthly followup visits; intervisit adherence data were downloaded from the dosing monitor and used to estimate therapeutic coverage and to identify correctable patterns of nonadherence. Subjects received token incentives and a small cash payment at each followup visit. Measures to prevent or treat side effects of doxycycline were dispensed free of charge. Study coordinators monitored safety and reinforced participation through between‐visit telephone calls.

Results

Of 463 eligible volunteers, 32 (7%) failed the FOH test and were excluded from the double‐blind phase. Among the 431 subjects randomized to treatment groups, 307 (71%) completed the 30‐month RCT and 124 discontinued the study drug prematurely. Nearly half of the dropouts returned for their 16‐ and 30‐month radiographs, resulting in loss to followup of 14.8% of randomized subjects. The 2 treatment groups did not differ significantly with respect to rates of discontinuation or retention. Therapeutic coverage over 30 months was very high in both groups.

Conclusion

The rate of discontinuation in this 30‐month RCT (29%) was lower than that of any DMOAD trial of ≥2 years duration published to date. The proportion of subjects for whom 30‐month radiographs were available (85%) and adherence to the dosing regimen (mean >80%) also were remarkably high.
Perfume
Authors: Weiss Kenneth M.
Published: December 2004

In Search of an Olfactory Mozart
Identifying SNPs predictive of phenotype using random forests
Authors: Bureau Alexandre , Dupuis Josée , Falls Kathleen , Lunetta Kathryn L. , Hayward Brooke , Keith Tim P. , Van Eerdewegh Paul
Published: December 2004

There has been a great interest and a few successes in the identification of complex disease susceptibility genes in recent years. Association studies, where a large number of single‐nucleotide polymorphisms (SNPs) are typed in a sample of cases and controls to determine which genes are associated with a specific disease, provide a powerful approach for complex disease gene mapping. Genes of interest in those studies may contain large numbers of SNPs that classical statistical methods cannot handle simultaneously without requiring prohibitively large sample sizes. By contrast, high‐dimensional nonparametric methods thrive on large numbers of predictors. This work explores the application of one such method, random forests, to the problem of identifying SNPs predictive of the phenotype in the case‐control study design. A random forest is a collection of classification trees grown on bootstrap samples of observations, using a random subset of predictors to define the best split at each node. The observations left out of the bootstrap samples are used to estimate prediction error. The importance of a predictor is quantified by the increase in misclassification occurring when the values of the predictor are randomly permuted. We extend the concept of importance to pairs of predictors, to capture joint effects, and we explore the behavior of importance measures over a range of two‐locus disease models in the presence of a varying number of SNPs unassociated with the phenotype. We illustrate the application of random forests with a data set of asthma cases and unaffected controls genotyped at 42 SNPs in ADAM33, a previously identified asthma susceptibility gene. SNPs and SNP pairs highly associated with asthma tend to have the highest importance index value, but predictive importance and association do not always coincide. Genet. Epidemiol. 28:171–182, 2005. © 2004 Wiley‐Liss, Inc.
The development and maintenance of exemplary formal mentoring programs in fortune 500 companies
Authors: Hegstad Christine D. , Wentling Rose Mary
Published: December 2004

This study sought to advance current mentoring research by examining the development and maintenance of exemplary formal mentoring programs in the nation's top performing companies. The ADDIE model of instructional systems design, which incorporates five steps from needs analysis to evaluation, formed the conceptual framework guiding the study. The methodology involved interviewing twenty‐nine participants within a sample of seventeen companies, selected from the Fortune 500 listing, housing exemplary formal mentoring programs. Results indicated that the steps of the ADDIE design system provide a useful framework in the development and maintenance of exemplary formal mentoring programs. A discussion of the results and recommendations for further research are presented.
The relationship between organizational commitment and organizational climate in manufacturing
Authors: McMurray Adela J. , Scott D. R. , Pace R. Wayne
Published: December 2004

The purpose of this study was to explore the relationship between organizational commitment and organizational climate. Subjects were chosen from three large Australian automotive component manufacturing companies. A questionnaire was administered to 1,413 employees from forty‐two countries of origin. A 97.8 percent response rate yielded 1,382 usable questionnaires. A significant correlation (.66) between organizational commitment and organizational climate was discovered.
Duration dependence in the exit rate out of unemployment in Belgium. Is it true or spurious?
Authors: Cockx Bart , Dejemeppe Muriel
Published: December 2004

On the basis of aggregate data for the early 1990s, we analyse the determinants of unemployment duration for laid‐off male workers in Wallonia (Belgium). Our results indicate that if ranking in recruitment occurs, the standard mixed proportional hazard specification can be too restrictive, leading to an overstatement of the extent of true negative duration dependence. We conclude that negative duration dependence is largely spurious. We also decompose the time variation of the hazard in (unobserved) compositional and direct cyclical and seasonal effects. We find counter‐cyclical variation in the quality of young workers, but none for the prime aged. Copyright © 2004 John Wiley & Sons, Ltd.
Modules, kinds, and homology
Authors: Rieppel Olivier
Published: December 2004

Developmental modules are best conceptualized as homeostatic property cluster natural kinds. As is true in other fields of biology, an individual may instantiate properties of various natural kinds. Through their dissociability, developmental modules can be recruited to function as evolutionary modules. The proper analogy to developmental modules, atoms, or biological species depends on the scope over which specific developmental modules allow generalizations. The nature of the relationship between developmental modules, evolutionary modules, and taxic (phylogenetic) homology are explored. Similarity of gene expression patterns and developmental pathways as captured by biological homology may support hypotheses of taxic homology, but not the other way around.J. Exp. Zool. (Mol. Dev. Evol). 304B:000–000, 2005.© 2005 Wiley‐Liss, Inc.
Hypoglycemic effect of extract of Hericium erinaceus
Authors: Wang Jinn Chyi , Hu Shu Hui , Wang Jih Terng , Chen Ker Shaw , Chia Yi Chen
Published: December 2004

Recent studies have determined that many types of mushroom (eg Hericium spp), may have important physiological functions in humans, including antioxidant activities, the regulation of blood lipid levels and reduction of blood glucose levels. In this study, a methanol extract of the fruiting bodies of Hericium erinaceus was adsorbed on silica gel columns and eluted using polarity gradients of chloroform/ethyl acetate/acetone/methanol. The major components of the extract were D‐threitol, D‐arabinitol and palmitic acid identified by their chromatographic profiles and spectroscopic characteristics. The methanol extract of H erinaceus was concentrated to remove solvent yielding a residue (referred to as HEM) which was added to the diet. The hypoglycemic effects of feeding HEM to streptozotocin‐induced diabetic rats were studied. Polydipsia was stronger in induced diabetic rats not fed HEM than in those receiving HEM. Rats fed with HEM had significantly lower elevation rates of blood glucose level than those not fed with HEM. The effects on blood glucose, serum triglyceride and total cholesterol levels were more significant in the rats fed daily with HEM at doses of 100 mg kg−1 body weight (bw) rather than 20 mg kg−1 bw (p < 0.05). Copyright © 2004 Society of Chemical Industry
Relationship of climate and genotype to seasonal variation in the glucosinolate–myrosinase system. II. Myrosinase activity in ten cultivars of Brassica oleracea grown in fall and spring seasons
Authors: Charron Craig S , Saxton Arnold M , Sams Carl E
Published: December 2004

Myrosinase catalyzes the hydrolysis of glucosinolates found in the Brassicaceae, generating a variety of bioactive reaction products that may aid in the prevention of some cancers and that are suppressive to soil‐borne plant pathogens. Two cultivars each of broccoli (Brassica oleracea L var italica), Brussels sprouts (B oleracea var gemmifera), cabbage (B oleracea var capitata), cauliflower (B oleracea var botrytis), and kale (B oleracea var acephala) were grown during two fall seasons and two spring seasons to determine if myrosinase activity varied by season. Regression models that included mean temperature and photosynthetic photon flux (PPF) during the growing seasons showed that climatic variables explained seasonal differences for myrosinase activity. Activity‐FW (FW = fresh weight; U g−1) and specific activity (U mg−1) were significantly (p ≤ 0.05) affected by season, botanical group and group × season. Activity‐FW had a negative linear relationship with temperature, and a positive linear but negative quadratic relationship with PPF. Specific activity had a positive linear and a negative quadratic relationship with both temperature and PPF. Therefore the influence of climatic factors on myrosinase activity in Brassica species may affect the potential benefits of the glucosinolate–myrosinase system. Copyright © 2004 Society of Chemical Industry
Fast Fatigue Testing of Spinal Implant Systems by the Load Stage Product (LSP)‐Test Method
Authors: Holzwarth U. , Lorenz S. , Schuh A.
Published: December 2004

The LSP test method was used to compare various surface treatments of spinal rods for dorsal spine implant systems. This test method allowed a fast testing. Result were given after one or two weeks in comparison to 6 to 8 months. Rods made of two different cp‐Titanium materials ( Ti‐2 and Ti‐4) were tested. Best results with a LSP value of 167 Mio. were achieved with Ti‐4 material, shot peened with steel balls and glass beads. In comparison the lowest LSP value showed 81 Mio with Ti‐2 material shot peened with glass beads only.

This kind of high speed testing reduced the typical development period from two years to at least 6 months.
Cortical laminar necrosis in childhood intracranial germ cell tumor survivors
Authors: Khong Pek‐Lan , Ng Kim‐Ching , Kwong Dora LW , Ooi Gaik‐Cheng , Chan Godfrey CF
Published: December 2004

We report two childhood germ cell tumor survivors treated for multifocal or large suprasellar tumors followed by the presentation of acute neurological deficits and extensive cortical laminar necrosis on magnetic resonance imaging (MRI), 7 and 34 months after cranial irradiation. This complication, though uncommon, represents another manifestation of delayed treatment‐related brain injury that can be catastrophic and leads to significant morbidity. © 2004 Wiley‐Liss, Inc.
Angiotensin II (AII) induced hypertension chemotherapy (IHC) for unresectable gastric cancer: With reference to resection after down staging
Authors: Sato Haruhiko , Sugiyama Katsuo , Hoshi Masahiko , Urushiyama Masanobu , Ishizuka Keiichi
Published: December 2004

Angiotensin II induced hypertension chemotherapy (IHC) is a drug delivery system for augmentation of anti‐cancer effects on the experimental basis of the functional difference of microcirculation between tumor and normal tissue. Blood flow in tumor tissue increased selectively when the blood pressure was elevated by the infusion of angiotensin II. Two randomized controlled trials (RCT) for advanced gastric cancer using AFM regimen; a combination of adriamycin (ADM), 5‐fluorouracil (5‐FU), and mitomycin (MMC), showed increased response tate by IHC (response rate: IHC/non‐IHC; 42.9% vs 10.5% in RCT‐1, and 31.3% vs 6.7% in RCT‐2, respectively). Toxicities were not different statistically between groups. In phase II for stage IVB gastric cancer patients (the criteria according to the General Rules of the Gastric Cancer Study of Japanese Research Society for Gastric Cancer), 5 complete response (CR) and 10 partial response (PR) (58%) were obseved out of 26 unresectable cases without prior chemotherapy. Moreover, 5 of 15 responders could receive curative gastrectomy and obtained conclusive down staging (19%). Here we discuss the role of enhancement of drug delivery for cancer chemotherapy on the basis of a series of clinical and experimental evidences.
Multidisciplinary approach to the treatment of unresectable breast cancer
Authors: Shen Zhen‐Zhou , Zhang Ya‐Wei , Pan Tian‐Xi , Xia Chuan‐Jiang
Published: December 2004

Between January 1960 and December 1990, 163 patients with locally advanced breast cancer (LABC) were treated by multidisciplinary treatment regimens. Forty‐six cases received preoperative intraarterial perfusion of cytotoxic drugs. Fifty‐four cases received preoperative systemic chemotherapy. Forty‐one cases received preoperative radiotherapy, and twenty‐two cases received both radiotherapy and chemotherapy. Preoperative systemic chemotherapy gives the best results. Postoperative chemotherapy and radiotherapy did not improve the survival rate as compared to the control group. The authors suggest that preoperative induction chemotherapy be used for LABC patients.
Role of radiotherapy following total mastectomy in patients with early breast cancer
Authors: Houghton J. , Baum M. , Haybittle J. L. ,   Closed Trials Working Party of the CRC Breast Cancer Trials Group
Published: December 2004

Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomized 2800 patients folowing mastectomy to immediate prophylactic radiotherapy (DXT group, n=1376) or control (WP group, n=1424). Although no difference in overall survival has been demonstrated, there is an increase in mortality in the irradiated patients from nonbreast cancer causes beyond 5 years. It is because of an increase in the number of deaths due to new nonbreast malignancies [RR=1.89 (1.18–3.05)] and to cardiac‐related disease [RR=1.52 (1.01–2.29)]. This increased cardiac death rate may be related to the use of orthovoltage, which has greater scatter. There was a significant increase in risk for those with left‐sided rather than right‐sided tumors in this subgroup [χ2(int) = 5.08; p = 0.02]. Local relapse was significantly reduced in those patients randomized to radiotherapy [RR=0.44 (0.39–0.51)]. Median survival following local relapse was 1.35 years in the DXT group and 2.66 years in the WP group (logrank p<0.001). Patients with the first relapse in the supraclavicular nodes had a particularly poor prognosis (median survival: DXT 0.69 years; WP 1.37 years). Almost 50% of patients who have had a recurrence on the chest wall or in the axilla and subsequently died have had disease at the same site at death, regardless of whether they had radiotherapy immediately following surgery. However, the actual number of patients dying with persistent disease is halved by the use of prophylactic radiotherapy (DXT 66; WP 143). Classic pathologic features such as tumor size, tumor grade, and nodal involvement help define those patients at high risk of local failure who should be recommended for immediate radiotherapy.
Does the method of management of papillary thyroid carcinoma make a difference in outcome?
Authors: DeGroot Leslie J. , Kaplan Edwin L. , Straus Francis H. , Shukla Manan S.
Published: December 2004

We have analyzed data on a group of 269 patients with papillary thyroid carcinoma followed on average for 12 years to determine (1) if a prognostic classification scheme can be used to predict an appropriate surgical approach; (2) the effect of treatment on prognosis; and (3) if patients with a “excellent” prognosis benefit from more extensive surgical resection and 131I ablation. Prognostic classification schemes developed by the American Joint Commission, Cady et al., Hay et al., the European Thyroid Association, and our own clinical class scheme each appropriately divided patients into risk category groups. With each system, some patients classified in the low risk group eventually died of the tumor. Considering the excellent but not perfect precision of the prognostic schemes, the need for detailed pathologic analysis, and ideally postoperative thyroid scanning, we conclude that the prognostic classification schemes do not allow the decision at the operating table regarding the appropriate extent of surgery. Patients followed at our institution, operated on by one of three experienced surgeons, and usually given 131I ablation were compared to other patients in the follow‐up group operated on by other surgeons and not routinely ablated. There were significantly fewer deaths and recurrences among the patients managed by our method. However, when the groups were restricted to those considering only patients who had more extensive surgery, postoperative 131I ablation, or both, the differences between the groups became insignificant. This finding indicates that the difference in prognosis, comparing patients treated at our institution and those initially treated elsewhere, was primarily due to the routine use of more extensive surgery and postoperative radioactive iodide ablation. Patients under age 45 with intrathyroidal disease or positive neck nodes and tumors less than 2.5 cm in diameter had an excellent prognosis, as shown by the absence of deaths due to tumor during the follow‐up period. However, extensive surgery and 131I ablation was associated with a significant reduction in recurrences. These data support the use of lobectomy plus contralateral subtotal lobectomy or near‐total thyroidectomy as the primary operative procedures for thyroid cancers larger than 1 cm in size and in patients beyond age 45; they also support the use of 131I ablation postoperatively to provide the best prognosis with reduction in deaths and recurrences.
Human neutrophil α‐defensin 4 inhibits HIV‐1 infection in vitro
Authors: Wu Zhibin , Cocchi Fiorenza , Gentles David , Ericksen Bryan , Lubkowski Jacek , DeVico Anthony , Lehrer Robert I. , Lu Wuyuan
Published: December 2004

Human neutrophil α‐defensin 4 (HNP4) is more effective than HNP1–3 in protecting human peripheral blood mononuclear cells from infection by both X4 and R5 HIV‐1 strains. HNP4 binds to both CD4 and gp120 approximately two orders of magnitude weaker than does HNP1, and is less effectively sequestered by glycosylated serum proteins than HNP1. These results suggest that the HIV‐1 inhibition by HNP4 stems at least partially from a unique and lectin‐independent property of HNP4 with CD4 and/or gp120. Our finding identifies an anti‐HIV‐1 property of HNP4 and may have implications in the development of new antiviral agents for AIDS therapy.
A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis
Authors: Kuroda Masahiko , Oikawa Kosuke , Ohbayashi Tetsuya , Yoshida Keiichi , Yamada Kazuhiko , Mimura Junsei , Matsuda Yoichi , Fujii-Kuriyama Yoshiaki , Mukai Kiyoshi
Published: December 2004

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) is an endocrine disruptor that produces a variety of toxic effects. We have isolated a mouse homolog of the hWAPL gene, termed mouse WAPL (mWAPL), as a target of TCDD by cDNA representational difference analysis from mouse embryonic stem cells. A statistically significant increase in mWAPL expression was observed at 0.1 μM TCDD in AhR−/− mouse embryonic fibroblast cells. Interestingly, at 1 μM TCDD, mWAPL mRNA levels decreased in AhR+/+ cells, but further increased in AhR−/− cells. hWAPL and mWAPL were highly expressed only in testes among normal tissue samples, and we observed mWAPL localization in the synaptonemal complex of testicular chromosomes. In addition, mouse testes decreased the expression of mWAPL mRNA after a single intraperitoneal injection of TCDD. Thus, mammalian WAPL such as hWAPL and mWAPL may be involved in spermatogenesis and be target genes mediating the reproductive toxicity induced by TCDD.
Mia40, a novel factor for protein import into the intermembrane space of mitochondria is able to bind metal ions
Authors: Terziyska Nadia , Lutz Thomas , Kozany Christian , Mokranjac Dejana , Mesecke Nikola , Neupert Walter , Herrmann Johannes M. , Hell Kai
Published: December 2004

Many proteins located in the intermembrane space (IMS) of mitochondria are characterized by a low molecular mass, contain highly conserved cysteine residues and coordinate metal ions. Studies on one of these proteins, Tim13, revealed that net translocation across the outer membrane is driven by metal‐dependent folding in the IMS [1]. We have identified an essential component, Mia40/Tim40/Ykl195w, with a highly conserved domain in the IMS that is able to bind zinc and copper ions. In cells lacking Mia40, the endogenous levels of Tim13 and other metal‐binding IMS proteins are strongly reduced due to the impaired import of these proteins. Furthermore, Mia40 directly interacts with newly imported Tim13 protein. We conclude that Mia40 is the first essential component of a specific translocation pathway of metal‐binding IMS proteins.
Ubiquitinated annexin A2 is enriched in the cytoskeleton fraction
Authors: Lauvrak Silje U. , Hollås Hanne , Døskeland Anne P. , Aukrust Ingvild , Flatmark Torgeir , Vedeler Anni
Published: December 2004

Annexin A2 is a multifunctional protein and its cellular functions are regulated by post‐translational modifications and ligand binding. When purified from porcine intestinal mucosa and transformed mouse Krebs II cells, SDS–PAGE revealed high‐molecular‐mass forms in addition to the 36 kDa protomer. These forms were identified as poly‐/multi‐ubiquitin conjugates of annexin A2, and ubiquitination represents a novel post‐translational modification of this protein. Subcellular fractionation of mouse Krebs II cells revealed an enrichment of annexin A2‐ubiquitin conjugates in the Triton X‐100 resistant cytoskeleton fraction, suggesting that ubiquitinated annexin A2 may have a role associated with its function as an actin‐binding protein.
Corporatism from the Firm Perspective: Employers and Social Policy in Denmark and Britain
Authors: MARTIN CATHIE JO
Published: December 2004

This is an evaluation of the impact of corporatist and pluralist employers' associations on firms' programmatic participation in active labour-market and social policies in Denmark and Britain. Drawing on semi-structured interviews with randomly-selected companies, it explores whether employers' associations engage differently with their constituent firms in corporatist and pluralist settings, and whether corporatist countries have an advantage in implementing active social policies. Variations in type of employer organization are found to constitute a determinant of cross-national differences in business attitudes towards the welfare state. Membership in a Danish employers' association confers an entirely different set of effects from membership in a British group and associational membership is a significant positive determinant of firm participation in Denmark but not in Britain. Active social policy has been viewed as a growth opportunity in a new issue area by the Danish ‘peak’ employers' association and its sectoral members. Although this association is losing some control over collective bargaining, its constituent associations have developed other functions, such as creating deliberative forums for managers, especially at the local level. The research also highlights the role of the state in the renegotiation and survival of corporatist institutional arrangements.
THE BLUEBEARD BAROMETER: CHARLES DICKENS AND CAPTAIN MURDERER
Authors: Barzilai Shuli
Published: December 2004

“You mustn't marry more than one person at a time, may you, Peggotty?”“Certainly not,” says Peggotty, with the promptest decision.“But if you marry a person, and the person dies, why then you may marry another person, mayn't you, Peggotty?”“You MAY,” says Peggotty, “if you choose, my dear. That's a matter of opinion.”—David Copperfield(1849–50)

THE FIRST TIME I HEARD OF CAPTAIN MURDERERwas in the Jerusalem Theater many years ago when the Welsh actor Emlyn Williams (1905–87) gave a reading of scenes from the works of Charles Dickens. Williams's performance was a recreation of the initiative of Dickens himself who, in the late 1850s, took on yet another activity and persona, that of the itinerant player, and began a series of public tours in which he read from his own works. Of all the pieces Williams performed on that occasion, the story of “a certain Captain Murderer” remains most vividly present to memory not only for its eerie atmosphere and plot but especially for its effect on the audience. I can still recall the collective gasp of horror, as well as the outbursts of laughter, that the story's denouement elicited from a captivated company of listeners.