bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic classification of spondylarthropathy and rheumatoid arthritis by synovial histopathology: A prospective study in 154 consecutive patients
Authors: Baeten Dominique , Kruithof Elli , De Rycke Leen , Vandooren Bernard , Wyns Bart , Boullart Luc , Hoffman Ilse E. A. , Boots Annemieke M. , Veys Eric M. , De Keyser Filip
Published: September 2004

Objective

To explore prospectively the value of synovial histopathology in comparison with the value of classic parameters for diagnostic classification of spondylarthropathy (SpA) and rheumatoid arthritis (RA) in patients with an atypical disease presentation.

Methods

Synovial biopsy samples were obtained from 154 consecutive patients presenting for diagnostic evaluation; 67 patients fulfilled the classification criteria for RA, SpA, or other well‐defined disease at the time of arthroscopy (cohort 1), and an additional 53 patients were classified after a full diagnostic reevaluation at 6 months (cohort 2). Synovial parameters with diagnostic value were identified in cohort 1 and were compared prospectively with classic diagnostic parameters in cohort 2.

Results

Staining with anticitrulline, staining with monoclonal antibody 12A (recognizing HLA–DR shared epitope–human cartilage glycoprotein 39263–275 complexes), and crystal deposition had positive predictive values (PPVs) for diagnosis of >90% in patients with an atypical disease presentation (cohort 2). Using these 3 parameters, a diagnosis was predicted by synovial histopathology in 39.6% of cohort 2 patients and turned out to be correct in 90.5% of these patients at 6 months of followup. Using a multiparameter model rather than single histopathologic parameters, even better results were obtained, with a diagnostic prediction in 79.2% of samples and a PPV of 81.0%. In comparison, a similar multiparameter model using classic diagnostic criteria rather than synovial histopathology performed poorly in cohort 2; the sensitivity was 56.6% and the PPV was 73.3%, with an inferior capacity to predict SpA. Especially for the presence of crystals and anticitrulline staining, the analysis of synovial tissue had a clear added value to the analysis of synovial fluid or serum in patients with an atypical presentation.

Conclusion

This proof‐of‐concept study indicates that synovial histopathology can contribute to the multiparametric diagnostic classification of inflammatory arthritis in patients with an atypical presentation.
Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down‐regulation by tumor necrosis factor α blockade in spondylarthropathy
Authors: Vandooren Bernard , Kruithof Elli , Yu David T. Y. , Rihl Markus , Gu Jieruo , De Rycke Leen , Van Den Bosch Filip , Veys Eric M. , De Keyser Filip , Baeten Dominique
Published: September 2004

Objective

To investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in spondylarthropathy (SpA) synovitis.

Methods

Paired samples of synovial biopsy tissue as well as serum and synovial fluid (SF) from 41 patients with SpA and 20 patients with rheumatoid arthritis (RA) and serum samples from 20 healthy controls were analyzed by immunohistochemistry and enzyme‐linked immunosorbent assay for the presence of MMPs 1, 2, 3, and 9 and TIMPs 1 and 2. In addition, sera from 16 patients with ankylosing spondylitis (AS) and peripheral synovitis and 17 patients with AS and exclusively axial involvement were analyzed. An additional cohort of SpA patients was analyzed at baseline and after 12 weeks of infliximab treatment.

Results

Staining for MMPs and TIMPs showed a cellular and interstitial pattern in the synovial lining and sublining layers that was similar between the RA and SpA patients. Involvement of MMPs and TIMPs in SpA synovitis was suggested by the correlation with cellular infiltration, vascularization, and cartilage degradation. Higher serum levels of MMPs 3 and 9 were revealed in SpA and RA patients as compared with healthy controls. Production of MMP‐3, but not MMP‐9, in the serum reflected the presence of peripheral synovitis, as indicated by 1) the correlation between serum levels, SF levels (which were 1,000‐fold higher than the serum levels), and synovial expression of MMP‐3, 2) the increased levels of MMP‐3 in AS patients with peripheral disease and not exclusively axial involvement, and 3) the correlation of serum and SF MMP‐3 with parameters of synovial, but not systemic, inflammation. The modulation of the MMP/TIMP system by tumor necrosis factor α (TNFα) blockade was confirmed by the down‐regulation of all MMPs and TIMPs in the synovium and a pronounced and rapid decrease of serum MMP‐3.

Conclusion

MMPs and TIMPs are highly expressed in SpA synovitis and mirror both the inflammatory and tissue‐remodeling aspects of the local disease process. Serum MMP‐3, originating from the inflamed joint, represents a valuable biomarker for peripheral synovitis. Modulation of the MMP/TIMP system by infliximab could contribute to the antiinflammatory and tissue‐remodeling effects of TNFα blockade in SpA.
Synthesis of proteoglycan 4 by chondrocyte subpopulations in cartilage explants, monolayer cultures, and resurfaced cartilage cultures
Authors: Schmidt Tannin A. , Schumacher Barbara L. , Klein Travis J. , Voegtline Michael S. , Sah Robert L.
Published: September 2004

Objective

To quantify the levels of proteoglycan 4 (PRG4) expression by subpopulations of chondrocytes from superficial, middle, and deep layers of normal bovine calf cartilage in various culture systems.

Methods

Bovine calf articular cartilage discs or isolated cells were used in 1 of 3 systems of chondrocyte culture: explant, monolayer, or transplant, for 1–9 days. PRG4 expression was quantified by enzyme‐linked immunosorbent assay of spent medium and localized by immunohistochemistry at the articular surface and within chondrocytes in explants and cultured cells.

Results

Superficial chondrocytes secreted much more PRG4 than did middle and deep chondrocytes in all cultures. The pattern of PRG4 secretion into superficial culture medium varied with the duration of culture, decreasing with time in explant culture (from ∼25 μg/cm2/day on days 0–1 to ∼3 μg/cm2/day on days 5–9), while increasing in monolayer culture (from ∼1 pg/cell/day on days 0–1 to ∼7 pg/cell/day on days 7–9) and tending to increase in transplant culture (reaching ∼2 μg/cm2/day by days 7–9). In all of the culture systems, inclusion of ascorbic acid stimulated PRG4 secretion, and the source of PRG4 was immunolocalized to superficial cells.

Conclusion

The results described here indicate that the phenotype of PRG4 secretion by chondrocytes in culture is generally maintained, in that PRG4 is expressed to a much greater degree by chondrocytes from the superficial zone than by those from the middle and deep zones. The marked up‐regulation of PRG4 synthesis by ascorbic acid may have implications for cartilage homeostasis and prevention of osteoarthritic disease. Transplanting specialized cells that secrete PRG4 to a surface may impart functional lubrication and be generally applicable to many tissues in the body.
Risk factors for symptomatic knee osteoarthritis fifteen to twenty‐two years after meniscectomy
Authors: Englund M. , Lohmander L. S.
Published: September 2004

Objective

To evaluate the influence of age, sex, body mass index (BMI), extent of meniscal resection, cartilage status, and knee load on the development of radiographically evident osteoarthritis (OA) of the knee and knee symptoms after meniscal resection.

Methods

We evaluated 317 patients with no cruciate ligament injury (mean ± SD age 54 ± 11 years) who had undergone meniscal resection 15–22 years earlier (followup rate 70%), with radiographic and clinical examination. The Knee injury and Osteoarthritis Outcome Score was used to quantify knee‐related symptoms. Sixty‐eight unoperated subjects identified from national population records were included as a reference group.

Results

Symptomatic radiographic OA (corresponding to Kellgren/Lawrence grade ≥2) was present in 83 of 305 operated knees (27%) and 7 of 68 control knees (10%) (relative risk 2.6, 95% confidence interval [95% CI] 1.3–6.1). Patients who had undergone total meniscectomy and subjects with obesity (BMI ≥30) had a greater likelihood of tibiofemoral radiographic OA than those who had undergone partial meniscal resection and those with a BMI <25, respectively. Furthermore, degenerative meniscal tear, intraoperative cartilage changes, and lateral meniscectomy were associated with radiographic OA more frequently than were longitudinal tear, absence of cartilage changes, and medial meniscectomy, respectively. Symptomatic tibiofemoral or patellofemoral radiographic OA was associated with obesity, female sex, and degenerative meniscal tear.

Conclusion

Contributing risk factors for OA development after meniscal resection are similar to risk factors for common knee OA. Systemic factors and local biomechanical factors interact. Obesity, female sex, and preexisting early‐stage OA are features associated with poor self‐reported and radiographic outcome. Partial meniscal resection is associated with less radiographic OA over time than is total meniscectomy.
First report of systemic reactive (AA) amyloidosis in a patient with the hyperimmunoglobulinemia D with periodic fever syndrome
Authors: Obici Laura , Manno Carlo , Muda Andrea Onetti , Picco Paolo , D'Osualdo Andrea , Palladini Giovanni , Avanzini Maria Antonietta , Torres Diletta , Marciano Sabrina , Merlini Giampaolo
Published: September 2004

Systemic reactive (AA) amyloidosis, leading to renal failure, is a severe complication of most hereditary periodic fever syndromes. The risk of developing this life‐threatening condition varies widely among these disorders, being higher for patients affected by familial Mediterranean fever and tumor necrosis factor receptor–associated periodic syndrome. In spite of an acute‐phase response during attacks, amyloidosis has never, to date, been described in patients affected with the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). This is the first report to describe the occurrence of renal AA amyloidosis causing severe nephrotic syndrome in a young Italian man affected with HIDS. The diagnosis of HIDS was established according to clinical, laboratory, and genetic criteria as required by the international Nijmegen HIDS registry. In this patient, 2 mutations in the mevalonate kinase gene were identified, one of which, the leucine‐to‐arginine substitution at codon 265, is novel.
Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS‐4 (aggrecanase 1) or ADAMTS‐5 (aggrecanase 2)
Authors: Chockalingam Priya S. , Zeng Weilan , Morris Elisabeth A. , Flannery Carl R.
Published: September 2004

Objective

To determine whether aggrecanase (ADAMTS) activities in articular cartilage can directly lead to the release of hyaluronan (HA) and hyaladherins (aggrecan G1 domain and link proteins), as may occur ex vivo during stimulation of cartilage explants with interleukin‐1 (IL‐1) or retinoic acid or in vivo in synovial joints during aging and joint pathology.

Methods

Bovine articular cartilage discs (live or freeze‐killed) were cultured in the presence of IL‐1 or were incubated in digestion buffer containing recombinant human ADAMTS‐4 (rHuADAMTS‐4; aggrecanase 1) or rHuADAMTS‐5 (aggrecanase 2). Culture media, digestion supernatants, and tissue extracts were assayed for sulfated glycosaminoglycan (sGAG) content and analyzed by Western blotting to detect aggrecanase‐generated G1 domain (using neoepitope monoclonal antibody AGG‐C1/anti‐NITEGE373) and link proteins (using monoclonal antibody 8‐A‐4), as well as by quantitative enzyme‐linked immunosorbent assays to detect aggrecanase‐generated G1 domain (G1‐NITEGE373) and HA.

Results

IL‐1 treatment of live cartilage explants induced a time‐dependent release of sGAG, aggrecanase‐generated G1 domain (G1‐NITEGE373), and HA into the culture media. Exposure of live or freeze‐killed articular cartilage discs to rHuADAMTS‐4 or rHuADAMTS‐5 resulted in a dose‐ and time‐dependent release of sGAG and hyaluronan from the tissue, accompanied by a concomitant release of functionally intact hyaladherins (aggrecan G1‐NITEGE373 and link proteins).

Conclusion

Coincident with aggrecanolysis, aggrecanase activities in articular cartilage may actuate the release of HA and associated hyaladherins, thereby further compromising the integrity of the cartilage matrix during degenerative joint diseases such as osteoarthritis.
CD4+CD25+ regulatory T cells in rheumatoid arthritis: Differences in the presence, phenotype, and function between peripheral blood and synovial fluid
Authors: van Amelsfort Jocea M. R. , Jacobs Kim M. G. , Bijlsma Johannes W. J. , Lafeber Floris P. J. G. , Taams Leonie S.
Published: September 2004

Objective

In mice, CD4+CD25+ regulatory T cells play a pivotal role in preventing autoimmunity. Regulatory T cells are also present and functional in healthy humans. We investigated the presence, phenotype, and function of CD4+CD25+ regulatory T cells in peripheral blood (PB) and synovial fluid (SF) from patients with rheumatoid arthritis (RA).

Methods

The presence and phenotype of CD4+CD25+ regulatory T cells were determined by flow cytometry. Anergy and suppressive activity were assessed by culturing CD4+CD25− and CD4+CD25+ T cells with anti‐CD3 monoclonal antibodies and antigen‐presenting cells, followed by proliferation and cytokine detection.

Results

The percentage of CD4+CD25+ T cells in RA SF was significantly increased compared with that in RA PB, and both of these percentages were higher than that in PB from controls. The cells in RA PB were similar in phenotype and function to CD4+CD25+ regulatory T cells from controls. In SF, however, ∼40–50% of CD4+CD25+ T cells expressed an activated phenotype, i.e., CD69+, class II MHC+, OX‐40+, with high levels of CTLA‐4 and glucocorticoid‐induced tumor necrosis factor receptor. These synovial CD4+CD25+ T cells displayed an increased suppressive capacity compared with blood CD4+CD25+ T cells. However, this enhanced suppressive activity was counterbalanced, because activated responder T cells from SF were less susceptible to CD4+CD25+ T cell–mediated suppression than were responder cells from PB.

Conclusion

We demonstrate that CD4+CD25+ regulatory T cells are present and functional in patients with RA, with higher numbers of regulatory T cells with increased suppressive activity found in SF compared with PB. These findings suggest a negative feedback system that is active at the site of inflammation. The balance between activated responder and regulatory T cells appears to influence the extent of immunoregulation in RA.
Gußasphalt‐Dichtsysteme in Anlagen zum Lagern, Abfüllen und Umschlagen wassergefährdender Stoffe – Neue allgemeine bauaufsichtliche Zulassungen
Authors: Kluge Ullrich
Published: September 2004

Anlagen, Anlagenteile und technische Schutzvorkehrungen für Anlagen zum Umgang mit wassergefährdenden Stoffen müssen Anforderungen aus verschiedenen Rechtsbereichen wie z. B. Wasserrecht, Baurecht, Arbeitsschutzrecht usw. erfüllen. Das Deutsche Institut für Bautechnik (DIBt) erteilt allgemeine bauaufsichtliche Zulassungen für Abdichtungsmittel zur Verwendung in Dichtkonstruktionen in Anlagen zum Lagern, Abfüllen und Umschlagen wassergefährdender Stoffe (LAU‐Anlagen). Die Anforderungen an die Materialien und die Prüfverfahren für deren Nachweis sind in den Zulassungsgrundsätzen bzw. Prüfprogrammen des DIBt niedergelegt.

Durch das DIBt wurden neue allgemeine bauaufsichtliche Zulassungen für Gußasphalt‐Dichtsysteme in LAU‐Anlagen erteilt.
Entwurfsprobleme bei einem Ventilationsschacht aus Stahlbeton
Authors: Dembiński Mariusz , Krüger Piotr , Łańczak Władysław
Published: September 2004

Es werden die Ergebnisse der rechnerischen Analyse der Stahlbetonkonstruktion eines Ventilationsschachts vorgestellt, der mit auf Stahlriegeln einer Lackiererei gestützten Kanälen verbunden ist. Als besondere Lösung wird der Einsatz von vorgespannten, elastisch‐verschiebbaren Auflagern mit Tellerfedern und einem Elastomergleitlager beschrieben. Die nach eigenem Entwurf konzipierten und ausgeführten Stützelemente ermöglichen gleichzeitig sowohl horizontale als auch vertikale Verformungen der Stahlbetonkonstruktion, ohne signifikanten Einfluß auf die Werte der Auflagerreaktionen zu nehmen.
Erdwiderstand bei beliebigem Wanddrehpunkt auf Grundlage der Hypoplastizität
Authors: Gutjahr Stephan , Hettler Achim
Published: September 2004

Numerische Simulationen mit der Finite‐Elemente‐Methode zeigen, daß sich bei einem beliebigen Wanddrehpunkt, der sich z. B. bei einer bodenmechanischen Einspannung einstellt, völlig andere Bruchmechanismen ergeben als bei klassischen Berechnungsmethoden. Man beobachtet tiefliegendes und hochliegendes Versagen sowie die entsprechenden Zwischenformen. Daraus ergeben sich Konsequenzen für die Mobilisierungskurven und die Erdwiderstandsbeiwerte. Die Berechnungen ergeben wesentlich höhere Erdwiderstände als nach klassischen Methoden.
Recommendations for accelerating global action to prevent folic acid–preventable birth defects and other folate‐deficiency diseases: Meeting of experts on preventing folic acid–preventable neural tube defects
Authors: Oakley Godfrey P. , Bell Karen N. , Weber Mary Beth
Published: September 2004

BACKGROUND

In April of 2003, The Micronutrient Initiative, in collaboration with several other organizations, convened a group of knowledgeable scientists and policy experts to discuss ways to accelerate the global pace at which countries implement effective and sustainable programs to prevent folic acid–preventable birth defects and other folate‐deficiency diseases. Programs implemented to date by fewer than 40 countries have prevented only 10% of the estimated 240,000 annual cases of folic acid–preventable spina bifida and anencephaly.

METHODS

Participants in this meeting summarized and presented scientific evidence showing that increased consumption of synthetic folic acid prevents a large proportion of spina bifida and anencephaly cases. They also reviewed related guidance and endorsements issued by national professional societies and advisory bodies as well as policies and programs implemented by some countries that have already demonstrated successful results in terms of reduced rates of neural tube defects and improved folate nutrition.

CONCLUSIONS

The group formulated and discussed recommendations and strategies for increasing the pace of neural tube defect prevention globally. The recommendations and strategies are published here. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Scientific evidence supporting folic acid fortification of flour in Australia and New Zealand
Authors: Oakley Godfrey P. , Weber Mary Beth , Bell Karen N. , Colditz Paul
Published: September 2004

BACKGROUND

Fortification of flour with folic acid is a safe, sustainable, and cost‐effective approach for preventing spina bifida and anencephaly, and it is likely to confer multiple health benefits to the adult population. Scientists and advocates are bringing this intervention to the attention of policymakers in countries around the world, and consequently the demand for sound, science‐backed policy rationale is increasing.

METHODS

We recently prepared this scientific review for scientists, physicians, and advocates who were promoting mandatory folic acid fortification of flour in Australia and New Zealand. This short document references the most relevant published scientific data and national and international recommendations from other countries and presents an argument for fortification based on demonstrated need, proven effectiveness, safety, and multiple health benefits.

CONCLUSIONS

With some modifications, this document could be utilized in other countries considering fortification of flour or other staple products with folic acid. Other useful tools can be found at The Micronutrient Initiative website at www.micronutrient.org. Birth Defects Research (Part A) 2004. © 2004 Wiley‐Liss, Inc.
Birth defects in Arkansas: Is folic acid fortification making a difference?
Authors: Simmons Caroline J. , Mosley Bridget S. , Fulton‐Bond Cynthia A. , Hobbs Charlotte A.
Published: September 2004

BACKGROUND

Since 1998, fortification of grain products with folic acid has been mandated in the United States, in an effort to reduce the prevalence of neural tube defects (NTDs). Published reports have shown a reduction in the prevalence of spina bifida since fortification was mandated, but no published studies have reported a reduction in birth defects, other than NTDs, that are postulated to be associated with folic acid deficiency. This study was performed to determine if fortification has reduced the prevalence of NTDs and other birth defects in Arkansas.

METHODS

Using data from the Arkansas Reproductive Health Monitoring System, prevalences were computed for thirteen specific birth defects with prior evidence supporting a protective effect of folic acid or multivitamins. Prevalences were calculated using data for live births to Arkansas residents for 1993–2000. Exposure to folic acid fortification was classified by birth year as “pre‐fortification” (1993–1995), “transition” (1996–1998) or “post‐fortification” (1999–2000). Logistic regression analysis was used to compute crude and adjusted prevalence odds ratios comparing the identified time periods.

RESULTS

Prevalences decreased between the pre‐ and post‐fortification periods for spina bifida, orofacial clefts, limb reduction defects, omphalocele, and Down syndrome, but only the decrease in spina bifida was statistically significant (prevalence odds ratio 0.56; 95% confidence interval, 0.37, 0.83).

CONCLUSION

In Arkansas, the prevalence of spina bifida has decreased since folic acid fortification of foods was implemented. Similar studies by other birth defects surveillance systems are needed to confirm a preventive effect of fortification for malformations other than spina bifida. Birth Defects Research (Part A) 70:559–564, 2004. © 2004 Wiley‐Liss, Inc.
Case fatality among infants with congenital malformations by lethality
Authors: Bol Kirk A. , Rickard Russel S. , Kirby Russell S.
Published: September 2004

OBJECTIVE

Infant mortality rates continue to show that congenital anomalies are the leading cause of infant death in the United States. However, studies of factors contributing to increased mortality across different types of congenital anomalies have been limited. The objective of this study was to assess whether the likelihood of infant mortality varied by maternal race and ethnic group while considering the severity of the birth defect.

METHODS

A retrospective cohort analysis was conducted using data from Colorado's statewide, population‐based birth defects surveillance system (CRCSN). The cohort included infants, born between 1995 and 2000 to Colorado resident mothers, who were diagnosed with major congenital malformations stratified by degree of lethality. Multiple logistic regression was performed for each level of lethality, and included the following potential explanatory variables: maternal race/ethnicity, clinical gestation, birth weight, maternal education level, maternal age, and sex of child.

RESULTS

Within the low/very low lethality cohort, maternal race/ethnicity of Black/non‐Hispanic was associated with increased risk of infant mortality, OR 2.81 (1.41–5.19), as were low and very low birth weight, OR 2.21 (1.12–4.04) and 19.31 (11.84–31.01), respectively. Maternal race/ethnicity was not a significant risk factor in either high or very high lethality groups; however, the interaction between birth weight and gestational age significantly increased the risk of mortality.

CONCLUSIONS

Through the use of statewide, population‐based birth defects surveillance data, a disparity in infant mortality has been identified in a specific subset of the population that could be investigated further and targeted for prevention activities. Birth Defects Research (Part A) 70:580–585, 2004. © 2004 Wiley‐Liss, Inc.
Medical records vs. interview responses: A comparative analysis of selected variables for linked birth defect cases
Authors: Ramadhani Tunu A. , Canfield Mark A. , Waller D. Kim , Case Amy P.
Published: September 2004

Background

Data pertaining to birth defects are subject to certain limitations depending on the collection method. This study compares the agreement of data from medical records and maternal interviews.

Methods

The medical records and maternal interviews were linked for 1017 deliveries. Prevalence, concordance and kappa coefficients were calculated for maternal gestational and non‐gestational diabetes, insulin use, seizures/epilepsy, Hispanic ethnicity, and infant/fetus sex.

Results

The prevalence of non‐gestational diabetes was 4.3% in the medical records and 3.4% in the maternal interviews, with 98.1% agreement. The prevalence of gestational diabetes was 7.9% in medical records and 9.2% in maternal interviews, with 94.3% agreement. Similar prevalences and high levels of agreement were observed between the two systems for infant/fetus sex and mother's Hispanic ethnicity. Although high concordance was observed for seizures/epilepsy, kappa value was moderate.

Conclusions

The availability of two distinct sources of data provides an exceptional opportunity to compare and validate both data sources. We found that the data for certain variables from maternal interviews strongly agreed with information from medical records. However, the extent of that agreement depended on the type of variable measured. Our results suggest that for some variables such as demographic variables, researchers can use either of the two data sources. Birth Defects Research (Part A) 70:592–596, 2004. © 2004 Wiley‐Liss, Inc.
Follow‐up survey of parents of children with major birth defects in New York State
Authors: Sharpe‐Stimac Monica , Wang Ying , Druschel Charlotte M. , Cross Philip K.
Published: September 2004

BACKGROUND

One of the objectives of the New York State birth defect surveillance system, the New York State Congenital Malformations Registry (CMR), is to identify children in need of special programs and assist prevention/intervention programs and services with evaluation. In 1999, the CMR started a statewide mass‐mailing program to inform parents of children with major birth defects about programs and support groups that might be helpful to them. A follow‐up survey by mail was conducted in 2002 to evaluate the usefulness of the mailing program.

METHODS

The survey was mailed between September and December of 2001 to parents of children born in 2001 and reported to the CMR with selected major birth defects. Non‐respondents were followed‐up by telephone.

RESULTS

Of the 226 eligible families, 54% (122) responded to the survey. Approximately 66% of responding parents stated that the information provided by the mailing program was helpful, and 48% had contacted and/or used the programs and services listed in the information sheets. Parents with children younger than 6 months of age at the time of mailing were more likely to find the information helpful, compared to parents with children 6 months of age or older. The majority of responding parents had contacted and/or used the Early Intervention Program.

CONCLUSION

The findings from the current survey show that the statewide information‐mailing program administered by CMR is helpful and useful to the families of children with major birth defects in New York State. Birth Defects Research (Part A) 70:597–602, 2004. © 2004 Wiley‐Liss, Inc.
„Und nur die Zukunft wird Klarheit bringen!”︁Der Fall des Biomediziners Jacques Benveniste aus dem Jahr 1988 im Blickfeld der wissenschaftlichen Publikationsorgane und der Laienpresse
Authors: Stahnisch Frank
Published: September 2004

Scientific disputes on the objectivity of research results are an integral part of the collective production of knowledge. One motivation to study cases of scientific controversy is the attempt to discover general patterns in the behaviour of participants and institutions involved in such controversies. Yet, for there to be a controversy, one must assume an important amount of social interaction, so much so that it renders it an essentially social phenomenon, which is accessible to historical study. Cases of obvious scientific fraud, in addition, are neither clear‐cut nor rare and the mere accusation of scientists by their peers frequently constitutes considerable examples of scientific debate. Together with this, it is often assumed that publication organs play a dominant role in directing the lines of scientific controversy, but their institutional significance and the task of individual editors remain widely unexplored. The present article studies the prominent Nature affair of the Parisian biomedical scientist Jacques Benveniste, both, from a perspective on scientific fraud and on the beginning and closure of scientific disputes. One of the most remarkable features of Benveniste's antibody dilution experiments was that they stroke at the foundations of modern physical and biomedical sciences. Could recent history of science actually resolve the case of the so‐called ‘memory of water’ phenomenon?
ON intramolecular acyl migration reaction in the development of prodrugs and the synthesis of difficult sequence‐containing bioactive peptides
Authors: Sohma Youhei , Hayashi Yoshio , Skwarczynski Mariusz , Hamada Yoshio , Sasaki Masato , Kimura Tooru , Kiso Yoshiaki
Published: September 2004

NOintramolecular acyl migration in Ser‐ or Thr‐containing peptides is a well‐known side reaction in peptide chemistry. It results in the mutual conversion of ester and amide bonds. Our medicinal chemistry study focused on the fact that the O‐acyl product can be readily converted to the original N‐acyl form under neutral or slightly basic conditions in an aqueous buffer and the liberated ionized amino group enhances the water solubility of O‐acyl products. Because of this, we have developed a novel class of “ON intramolecular acyl migration”‐type water‐soluble prodrugs of HIV‐1 protease inhibitors. These prodrugs released the parent drugs via a simple chemical mechanism with no side reaction. In this study, we applied this strategy to important cancer chemotherapeutic agents, paclitaxel and its derivatives, to develop water‐soluble taxoid prodrugs, and found that these prodrugs, 2′‐O‐isoform of taxoids, showed promising results with higher water solubility and proper kinetics in their parent drug formation by a simple pH‐dependent chemical mechanism with ON intramolecular acyl migration. These results suggest that this strategy would be useful in toxicology and medical economics.

After the successful application of ON intramolecular acyl migration in medicinal chemistry, this concept was recently used in peptide chemistry for the synthesis of “difficult sequence‐containing peptides.” The strategy was based on hydrophilic O‐acyl isopeptide synthesis followed by the ON intramolecular acyl migration reaction, leading to the desired peptide. In a model study with small, difficult sequence‐containing peptides, synthesized “O‐acyl isopeptides” not only improved the solubility in various media and efficiently performed the high performance liquid chromatography purification, but also altered the nature of the difficult sequence during SPPS, resulting in the efficient synthesis of O‐acyl isopeptides with no complications. The subsequent ON intramolecular acyl migration of purified O‐acyl isopeptides afforded the desired peptides as precipitates with high yield and purity. Further study of the synthesis of a larger difficult sequence‐containing peptide, Alzheimer's disease‐related peptide (Aβ1–42), surprisingly showed that only one insertion of the O‐acyl group drastically improved the unfavorable nature of the difficult sequence in Aβ1–42, and achieved efficient synthesis of 26‐O‐acyl isoAβ1–42 and subsequent complete conversion to Aβ1–42 via the ON intramolecular acyl migration reaction of 26‐O‐acyl isoAβ1–42. This suggests that our new method based on ON intramolecular acyl migration is an important method for the synthesis of difficult sequence‐containing bioactive peptides. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004
Raman study of poly(alanine‐glycine)‐based peptides containing tyrosine, valine, and serine as model for the semicrystalline domains of Bombyx mori silk fibroin
Authors: Taddei Paola , Asakura Tetsuo , Yao Juming , Monti Patrizia
Published: September 2004

For a deeper insight into the structure of Bombyx mori silk fibroin, some model peptides containing tyrosine (Y), valine (V), and serine (S) in the basic (AG)n sequence were synthesized by the solid‐phase method and analyzed by Raman spectroscopy in order to clarify their conformation and to evaluate the formation and/or disruption of the ordered structure typical of B. mori silk fibroin upon incorporation of Y, V, and S residues into the basic (AG)n sequence. The Raman results indicated that the silk I structure remains stable only when the Y residue is positioned near the chain terminus; otherwise, a silk I → silk II conformational transition occurs. The peptides AGVGAGYGAGVGAGYGAGVGAGYG(AG)3 and (AG)3YG(AG)2VGYG(AG)3YG(AG)3 treated with LiBr revealed a prevalent silk II conformation; moreover, the former contained a higher amount of random coil than the latter. This result was explained in relation to the different degrees of interruption of the (AG)n sequence. The Raman analysis of the AGSGAG‐containing samples confirmed that the AGSGAG hexapeptide is a good model for the silk II crystalline domain. As the number of AGSGAG repeating units decreased, the random coil content increased. The study of the Y domain (I850/I830 intensity ratio) allowed us to hypothesize that in the packing characteristic of Silk I and Silk II conformations the Y residues experience different environments and hydrogen‐bonding arrangements; the packing typical of silk I structure traps the tyrosyl side chains in environments more unfavorable to phenoxyl hydrogen‐bonding interactions. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
In vitro T‐cell immunogenicity of oligopeptides derived from the region 92–110 of the 16‐kDa protein of Mycobacterium tuberculosis
Authors: Bősze Szilvia , Caccamo Nadia , Majer Zsuzsa , Mező Gábor , Dieli Francesco , Hudecz Ferenc
Published: September 2004

The 16‐kDa protein of Mycobacterium tuberculosis provokes specific immune responses; it is thus a target for the development of peptide‐based diagnostic reagents and subunit vaccines. Previous studies have demonstrated the presence of several regions containing murine and human T‐cell epitopes. Within the 91–110 immunodominant domain, we found that peptides comprising the sequence of 91SEFAYGSFVRTVSL104 elicit specific T‐cell responses in both human T‐cell clones and human peripheral blood mononuclear cells (PBMC) from PPD+ (purified protein derivative) individuals. Elongation of this peptide towards the C‐terminal end did not provide more effective peptides, but the removal of residue 91Ser resulted in an almost complete loss of functionality. However, the introduction of an acetyl group at the N‐terminal of residue 92Glu produced a shorter peptide (Ac‐92EFAYGSFVRTVSL104) exhibiting properties required for efficient T‐cell responses. CD measurements indicated that peptide 91SEFAYGSFVRTVSLPVGADE110 adopts a helical conformation in triflouroethanol. We found that the N‐terminal part of this sequence plays a major role in the induction of proliferative T‐cell responses and is responsible for the highly ordered, helical secondary structure. The “lead” structure described here could also be considered in the development of synthetic peptides or multicomponent peptide mixtures for the early detection, monitoring, or preventing Mycobacterium tuberculosis infection with optimized T‐cell response‐provoking capacity. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004
Der Lotus‐Effekt: Selbstreinigende Oberflächen und ihre Übertragung in die Technik
Authors: Barthlott Wilhelm , Cerman Zdenek , Stosch Anne Kathrin
Published: September 2004

Durch die Kombination von Mikro‐ und Nanostrukturen mit einer hydrophoben Oberflächenchemie lassen sich heute technische Oberflächen mit erstaunlichen Eigenschaften herstellen. Diese Materialien sind extrem unbenetzbar; Schmutz kann durch einfaches Abspülen von ihnen entfernt werden. Die Idee zu einer solchen Entwicklung kam aus der Natur, denn Pflanzen mit selbstreinigenden Eigenschaften existieren schon seit Jahrmillionen. Doch erst vor wenigen Jahren konnte ihr Geheimnis entschlüsselt und in die Technik übertragen werden. Seitdem wird weltweit an der Umsetzung und Weiterentwicklung von selbstreinigenden Materialien gearbeitet, erste Produkte sind bereits erfolgreich auf dem Markt und mit der Marke Lotus‐Effekt® gekennzeichnet.
Eine Delfinhaut für Schiffe: Umweltneutrales Antifouling
Authors: Baum Christof , Siebers Dietrich , Fleischer Lutz‐Günther , Meyer Wilfried
Published: September 2004

Seit Beginn der Schifffahrt müssen Anstrengungen unternommen werden, um den Bewuchs an Schiffen möglichst gering zu halten. Der zunehmende weltweite Austausch von Waren über den Seeweg und unsere steigenden Ansprüche an die Nachhaltigkeit wirtschaftlichen Handelns erfordern umweltverträglichere Wege zur Bewuchsbekämpfung an Schiffen als bisher. Die ungiftige Delfinhaut gibt neue Impulse für das bionische Design von Bewuchsschutzfarben. Sie besticht vor allem durch ihre physikalischen Bewuchsschutzstrategien, die sich auf Kontaktflächenreduktion und kohäsives Strukturversagen zurückführen lassen.
Bionik und Wirtschaftlichkeit: Versuch einer Annäherung
Authors: Küppers Udo
Published: September 2004

Die Befragung von Produktentwicklern zeigt, dass für bionische Produkte durchaus ein Marktpotenzial vorhanden ist. Jedoch sind weitere Anstrengungen erforderlich, um diese innovative und zukunftsweisende Methode zur Produktentwicklung in Ausbildung und wirtschaftlicher Anwendung zu festigen. Strukturierte Entwicklungsanleitungen wie die Ähnlichkeitsmatrix können helfen, ein systematisches, bionisches Entwickeln zeiteffizient und fehlertolerant zu steuern. Vernetztes Denken in komplexen Systemen ist hierzu ein Schlüsselelement und kann durch eine so genannte “Korrespondenz des Lernens" gefördert werden.
Flusspferdhaut mit Lichtschutzfaktor
Authors: Knoll Ulrike
Published: September 2004

In der Hitze Afrikas verfärbt sich die Haut der Flusspferde scharlachrot – doch die Kolosse leiden nicht an Sonnenbrand. Vielmehr quillt aus ihren Poren vorbeugend eine “Body‐Lotion”, die den behäbigen Körper vor UV‐Strahlung abschirmt und sogar desinfiziert.
Nicht Fisch, nicht Fleisch, und doch gesund
Authors: Brennicke Axel
Published: September 2004

Bisher konnten nur Fische große mehrfach ungesättigte Fettsäuren synthetisieren. Jetzt gelang es, diese für die menschliche Gesundheit notwendigen Fettsäuren auch in Pflanzen zu produzieren. Dadurch könnte auf lange Sicht die Abhängigkeit von der schwindenden Ressource Fisch gemindert werden.
Transgene Schweine
Authors: Brennicke Axel
Published: September 2004

Jetzt ist es gelungen, Schweinefleisch ebenfalls mit den begehrten “gesunden Fetten” anzureichern: Ein Gen aus Spinat erhöht den Gehalt an ungesättigten Fettsäuren in transgenen Schweinen um mehr als das Zehnfache.
SMP‐Cell: Funktionsanalyse am laufenden Band
Authors: Wiemann Stefan
Published: September 2004

Im Nationalen Genomforschungsnetz (NGFN) hat die systematisch‐methodologische Plattform SMP‐Cell eine “Functional Genomics Pipeline” zur systematischen Identifizierung von krankheitsrelevanten menschlichen Genen etabliert. Zum Einsatz kommen hier vorwiegend Technologien der molekularen und zellulären funktionellen Genomanalyse.
Nektar für die Verteidigung
Authors: Irsch Wilhelm
Published: September 2004

Einige Akazienarten verteidigen sich trickreich gegen Fraßfeinde: Entweder beherbergen sie permanent ganze Ameisenkolonien oder sie locken bei Bedarf Ameisen aus der Umgebung an. Die Pflanzen beköstigen ihre Beschützer mit süßem Blattnektar und bieten ihnen eine Unterkunft. Dafür vertreiben oder töten die Ameisen die Fraßfeinde der Pflanze.
Life insurance, living benefits, and physician‐assisted death
Authors: Parker Frederick R. , Rubin Harvey W. , Winslade William J.
Published: September 2004

One of the most significant concerns about the legalization of physician‐assisted death in the United States relates to the possibility that a chronically or terminally ill person would choose to end her or his life for financial reasons. Because we believe that the life insurance industry is uniquely poised to help minimize any such incentive, we submit that it has a moral obligation to do so. In particular, we propose that the industry encourage greater flexibility in the payout of policy benefits in the event an insured should be diagnosed with a terminal illness or suffer from intractable pain. Copyright © 2004 John Wiley & Sons, Ltd.
Suicidality in adolescence: review and legal considerations
Authors: Judge Beth , Billick Stephen Bates
Published: September 2004

Adolescence is a unique developmental stage in which suicidality first emerges as a public health problem. The increasing trend of teenage suicide since the 1950s has only relented in the past ten years. The risk factors for adolescent suicide, suicidal ideation, and suicide attempts and an approach to assessing the suicidal adolescent for risk of future self‐harm are reviewed. Treatment consists of ensuring safety and then treating the underlying psychiatric, psychological, and interpersonal disturbances. Issues of consent, confidentiality, and malpractice actions are addressed. Copyright © 2004 John Wiley & Sons, Ltd.
Constructing common ground and re‐creating differences between professional and indigenous communities in the Andes
Authors: Craps Marc , Dewulf Art , Mancero Monica , Santos Enrique , Bouwen René
Published: September 2004

Multi‐actor initiatives aiming at environmental sustainability and social equity, face complex tensions between institutionalized decision‐makers, backed up by expert knowledge, and communities with locally embedded knowledge and interests. Despite the importance given to community participation, successful experiences are limited in number, scope and duration. Experts are confronted with the paradox that they exclude local communities with the strategies and languages they use to include them.

This study is based on the long‐term experiences of the authors with a multi‐actor initiative in southern Ecuador on sustainable rural drinking water management. They were involved as action‐researchers, facilitating multiparty interactions and supporting reflective practice among the participants.

The article shows how multiparty processes construct identities, workforms, structures and activities that cross the boundaries between communities of expert and indigenous practice, even in the exceptionally unequal conditions of the Andes, where inequalities between these communities are deeply rooted in history. Such transitions were taken as opportunities to look for common ground between different communities‐of‐practice whilst, at the same time, contradictions could come to the fore. As inequalities tend to be confirmed through interactions, not only inside but also outside the multi‐actor initiative, they cannot be resolved definitively by a multiparty project. Under those circumstances a social constructionist approach, calling the attention to the constructed nature of mutual perceptions and relationships, was highly inspiring for the authors‐facilitators to keep the reflection and dialogue among the participants in the process going‐on. Copyright © 2004 John Wiley & Sons, Ltd.
Conferencing in schools: punishment, restorative justice, and the productive importance of the process of conversation
Authors: Drewery Wendy
Published: September 2004

During the decade to 1999 in New Zealand, schools experienced more than doubling of the rates of suspension and exclusion. The higher suspension rates of Maori, males and in low decile schools were of particular concern. The Ministry of Education enacted a variety of responses to this situation, including encouraging the use of restorative conferencing in schools. This article builds on learning from the Restorative Conferencing in Schools Trial and shows how the process of a conversation can be productive of more and less peaceable relationships. It is argued that school communities are uniquely placed in civic life, and that it is worthwhile considering restorative conferencing and restorative practices more generally in relation to their behaviour management and disciplinary functions. Restorative practices are advanced from a social constructionist position, which is a very different philosophy from the philosophy of punishment and judgement that dominates in many schools. Copyright © 2004 John Wiley & Sons, Ltd.
NMR and Modeling Studies of Protein–Carbohydrate Interactions: Synthesis, Three‐Dimensional Structure, and Recognition Properties of a Minimum Hevein Domain with Binding Affinity for Chitooligosaccharides
Authors: Aboitiz Nuria , Vila‐Perelló Miquel , Groves Patrick , Asensio Juan Luis , Andreu David , Cañada Francisco Javier , Jiménez‐Barbero Jesús
Published: September 2004

HEV32, a 32‐residue, truncated hevein lacking eleven C‐terminal amino acids, was synthesized by solid‐phase methodology and correctly folded with three cysteine bridge pairs. The affinities of HEV32 for small chitin fragments—in the forms of N,N′,N′′‐triacetylchitotriose ((GlcNAc)3) (millimolar) and N,N′,N′′,N′′′,N′′′′,N′′′′′‐hexaacetylchitohexaose ((GlcNAc)6) (micromolar)—as measured by NMR and fluorescence methods, are comparable with those of native hevein. The HEV32 ligand‐binding process is enthalpy driven, while entropy opposes binding. The NMR structure of ligand‐bound HEV32 in aqueous solution was determined to be highly similar to the NMR structure of ligand‐bound hevein. Solvated molecular‐dynamics simulations were performed in order to monitor the changes in side‐chain conformation of the binding site of HEV32 and hevein upon interaction with ligands. The calculations suggest that the Trp21 side‐chain orientation of HEV32 in the free form differs from that in the bound state; this agrees with fluorescence and thermodynamic data. HEV32 provides a simple molecular model for studying protein–carbohydrate interactions and for understanding the physiological relevance of small native hevein domains lacking C‐terminal residues.
Disaccharide Mimetics of the Aminoglycoside Antibiotic Neamine
Authors: Venot Andre , Swayze Eric E. , Griffey Richard H. , Boons Geert‐Jan
Published: September 2004

A highly convergent approach has been employed for the facile synthesis of a library of 24 disaccharides that are α(1–3), β(1–3), α(1–4), or β(1–4) linked and contain 2–4 amino groups. Fourier‐transformation ion cyclotron resonance mass spectrometry (FT‐ICR MS) has been used to determine dissociation constant (Kd) values for the binding of the disaccharides to a prototypical fragment of 16S ribosomal RNA. Several derivatives bound with affinities similar to that of neamine. Structure–activity relationships have revealed the substitution pattern that is important for high‐affinity binding. The compounds described here are unique lead compounds for the design of novel aminoglycoside antibiotics.