bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Himalayan rabbit (Oryctolagus cuniculus L.): spontaneous incidences of endpoints from prenatal developmental toxicity studies
Authors: Viertel B. , Trieb G. 
Published: February 2003

The historical database represents the spontaneous, i.e. normal changes of characters, in laboratory animals, and is a must for the assessment of toxic effects of compounds. For the Himalayan rabbit (CHBB:HM, SPF) background data were collected from the control groups of regulatory studies between 1968-1999 in the Biberach laboratory of Boehringer Ingelheim (Germany). In the present study these data were compared with the background data from the years 1974-1984, with those from the Ingelheim laboratory, Germany (1977-1984) and those from the breeding colony at Kawanishi, Japan (1971-1991, 1972-1984). Fertility in the Biberach laboratory was relatively constant through the years, due to the strict breeding system. Litter parameters (corpora lutea, implantations and viable fetuses), including fetal sex distribution and fetal weight, were constant in the Biberach laboratory through the years and compared well with the data from Ingelheim and Kawanishi. From these three laboratories the results of spontaneous changes in fetal morphology above 0.1% incidence suggest a pattern of deviations from the Bauplan (fundamental body plan). These comprise synosteosis of sternebrae, lumbar (additional) ribs, hypoplasia of 12th rib, status of ossification, aplasia of gall bladder, hypoplasia of gall bladder, incompletely subdivided lung, dilated ventricle of heart, deviations at the A. carotis and at the aortic arch and flexure of paw. The absence of a time-dependent statistical trend indicates that the spontaneous change of endpoints remained constant through the time axis. Comparison with the spontaneously changed fetal morphology of the other strains (NZW, JW, SF rabbits) does not provide support for their being a totally strain-specific pattern, and this pattern may be closer to the species than specific to a single strain. The firm patterns of deviations in fetal morphology provide suitable and valuable markers for assessing toxic effects on ontogenesis. According to our experience these morphological endpoints react very sensitively to teratogenic compounds, which is demonstrated by increased incidences. Our knowledge of evolution of organisms and of mechanisms leading to morphological deviations points to a strict selection of phenotypes. For laboratory animals the decisive selection factors are defined by man. These are nutritive factors, environmental conditions, the mating system, handling and treatment, and experimental design. All these factors have to be held constant through the years, which is an absolute pre-condition for the application of valid historical data. The Himalayan rabbit is highly suitable for use in developmental toxicity studies due to the stability of reproductive data within the same laboratory over a period of more than 30 years, due to the similarity of reproductive data among three different laboratories, and due to an absence of relevant differences to the reproductive data of other rabbit strains.
Biomineralisation von Einzellern: eine außergewöhnliche Membranbiochemie zur Produktion anorganischer Nano‐ und Mikrostrukturen
Authors: Bäuerlein Edmund 
Published: February 2003

AbstractDie Natur hat es im Laufe ihrer Entwicklung mit einzigartiger Erfindungsgabe verstanden, auch anorganische Strukturen in vielfältigen Formen zu bilden. Jede Art, die biogene Mineralien hervorbringt, erzeugt diese in einer für sie spezifischen Form, die demnach offensichtlich biologisch kontrolliert ist. Es wird angenommen, dass sowohl die Synthese als auch die Form eines jeden biogenen Materials genetisch programmiert und gesteuert sind. Dies zu untersuchen und die Mechanismen der Biomineralisation zu beschreiben ist erst möglich geworden, seitdem moderne Methoden in der Biologie zu Verfügung stehen. Einzeller wie magnetische Bakterien, Kalkalgen und Kieselalgen, die zu den einfachsten Lebewesen gehören, eignen sich in besonderem Maße, mit diesen Methoden untersucht zu werden. In ihnen entstehen Kristalle und Verbundmaterialien aus Proteinen und amorphen anorganischen Polymeren, welche in der anorganischen Chemie bis heute unbekannt sind.
Biomineralization of Unicellular Organisms: An Unusual Membrane Biochemistry for the Production of Inorganic Nano‐ and Microstructures
Authors: Bäuerlein Edmund 
Published: February 2003

AbstractWith evolution, Nature has ingeniously succeeded in giving rise to an impressive variety of inorganic structures. Every organism that synthesizes biogenic minerals does so in a form that is unique to that species. This biomineralization is apparently biologically controlled. It is thus expected that both the synthesis and the form of every specific biogenic mineral is genetically determined and controlled. An investigation of the mechanism of biomineralization has only become possible with the development of modern methods in molecular biology. Unicellular organisms such as magnetic bacteria, calcareous algae, and diatoms, all of which are amongst the simplest forms of life, are particularly suited to be investigated by these methods. Crystals and composites of proteins and amorphous inorganic polymers are formed as complex structures within these organisms; these structures are not known in conventional inorganic chemistry.
Effects of dowels produced from various materials on withdrawal strength in MDF and Pb
Authors: Uysal Burhanettin , Özçifçi Ayhan 
Published: February 2003

AbstractWood dowels are commonly used in the construction furniture, but little information is available about the additive effects of dowels on the ultimate withdrawal strength of single or multidowel joints. This study was carried out to determine the tensile strength of 10‐mm‐diameter dowels produced from medium‐density fiberboard (MDF), plywood, scotch pine (Pinus sylvestris L.), and beech (Fagus orientalis lipsky), bonded parallel and vertical to the surface of MDF and particleboard (Pb) with poly(vinyl acetate) (PVAc) and Desmodur‐VTKA (D‐VTKA). Tensile strength was applied to the dowels according to the procedure in the ASTM‐D 1037 standard. The effects of dowel species, direction of tensile, composite material, and type of adhesive on tensile strength were determined. The results showed that the highest tensile strength was obtained in beech dowels bonded vertically with PVAc adhesive to the surface of MDF at 7.91 N/mm2. If the dowels used in furniture production are subjected to great tensile strength, beech dowels bonded with PVAc adhesive on MDF should be used. However, when dowels produced from MDF and plywood waste are used, they also can produce positive results. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 531–535, 2003
Estimating crystallinity in high density polyethylene fibers using online Raman spectroscopy
Authors: Paradkar R. P. , Sakhalkar S. S. , He X. , Ellison M. S. 
Published: February 2003

AbstractOnline Raman spectra, obtained at different points along the spin line during pilot‐scale nonisothermal melt spinning of high density polyethylene (HDPE) fibers, are presented for the first time. The fraction of the crystalline phase corresponding to each spectrum was determined from the normalized integrated intensity of the 1418 cm−1 Raman band. It is well established that this band represents the orthorhombic crystalline phase in polyethylene. The estimates of percent crystallinity obtained from decomposition of the Raman spectrum were compared with the percent crystallinity from differential scanning calorimetry (DSC) measurements. It is concluded that online Raman spectroscopy can be successfully used to monitor the development of crystallinity in HDPE fibers as a function of distance from the spinneret. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 545–549, 2003
Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor α–neutralizing agents
Authors: Slifman Nancy R. , Gershon Sharon K. , Lee Jong‐Hoon , Edwards Evelyne T. , Braun M. Miles 
Published: February 2003

AbstractObjectiveTumor necrosis factor α (TNFα) has been implicated in the pathogenesis of certain inflammatory diseases. Two TNFα‐neutralizing agents are licensed in the US. Infliximab is licensed for the treatment of Crohn's disease (CD) and, when used with methotrexate, for the treatment of rheumatoid arthritis (RA). Etanercept is licensed for the treatment of RA, including juvenile RA, and, more recently, was licensed for the treatment of psoriatic arthritis. Because of the potential for decreased host resistance to infectious agents due to treatment with anti‐TNFα agents, we sought to evaluate postlicensure cases of opportunistic infection, including Listeria monocytogenes, in patients treated with these products.MethodsThe FDA Adverse Event Reporting System, a passive monitoring system, was reviewed to identify all reports of adverse events (through December 2001) associated with L monocytogenes infection in patients treated with infliximab or etanercept.ResultsFifteen cases of L monocytogenes infection associated with infliximab or etanercept treatment were identified. In 14 of these cases, patients had received infliximab. The median age of all patients was 69.5 years (range 17–80 years); 53% were female. Six deaths were reported. Among patients for whom an indication for use was reported, there were 9 patients (64%) with RA and 5 patients (36%) with CD (information was not reported for 1 patient). All patients for whom information was reported were receiving concurrent immunosuppressant drugs.ConclusionPostlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFα‐neutralizing agents, particularly infliximab.
Articular cartilage repair by gene therapy using growth factor–producing mesenchymal cells
Authors: Gelse Kolja , von der Mark Klaus , Aigner Thomas , Park Jung , Schneider Holm 
Published: February 2003

AbstractObjectiveTo investigate the repair of partial‐thickness lesions in rat articular cartilage by combining cell transplantation with transfer of growth factor complementary DNA (cDNA).MethodsMesenchymal cells isolated from rib perichondrium were infected ex vivo with adenoviral vectors carrying bone morphogenetic protein 2 (BMP‐2) or insulin‐like growth factor 1 (IGF‐1) cDNA. The cells were suspended in fibrin glue and applied to mechanically induced partial‐thickness cartilage lesions in the patellar groove of the rat femur. The filling of the defects was quantified and the quality and integration of the newly formed tissue were assessed by histochemical and immunohistochemical methods. Uninfected cells or cells infected with a LacZ reporter gene vector served as controls.ResultsTransplanted cells were able to attach to the wounded articular cartilage and were not displaced from the lesions by joint movement. Cells infected with both adenoviral vectors AdBMP‐2 and AdIGF‐1 produced repair cartilage of hyaline morphology containing a type II collagen–positive but type I collagen–negative proteoglycan‐rich matrix that restored the articular surface in most lesions. Uninfected cells either failed to fill up the defects or formed fibrous tissue mainly composed of type I collagen. Excessive cells were partially dislocated to the joint margins, leading to osteophyte formation there if AdBMP‐2–infected cells were used. These adverse effects, however, were not seen with AdIGF‐1–infected cells.ConclusionStimulation of perichondrium‐derived mesenchymal cells by transfer of growth factor cDNA in a partial‐thickness defect model allows for satisfactory cartilage restoration by a repair tissue comparable with hyaline articular cartilage.
Synthesis of insulin‐like growth factor binding protein 3 in vitro in human articular cartilage cultures
Authors: Eviatar Tamar , Kauffman Hannah , Maroudas Alice 
Published: February 2003

AbstractObjectiveTo quantify the rate of synthesis of insulin‐like growth factor binding protein 3 (IGFBP‐3) and insulin‐like growth factor 1 (IGF‐1) by in vitro cultures of normal and osteoarthritic (OA) human articular cartilage.MethodsLevels of IGF‐1 and IGFBP‐3 in media from in vitro cultures of human cartilage were determined by radioimmunoassay (RIA). IGFBPs were characterized by immunoblots and ligand blots. Ultrafiltration and RIA analysis of synovial fluid (SF) samples and washings of cartilage samples ex vivo were used to calculate partition coefficients and to estimate the amount of IGF‐1 and IGFBP‐3 in cartilage in vivo.ResultsOA cartilage synthesized 150 ng of IGFBP‐3 per gm of cartilage per day, compared with 50 ng synthesized by normal cartilage. The surface zone of normal cartilage produced more IGFBP‐3 than did the deep zone. Immunoblots and ligand blots confirmed the presence of IGFBP‐3. IGFBP‐3 synthesis was stimulated by exogenous IGF‐1. No freshly synthesized IGF‐1 was detected. The quantities of IGF‐1 and IGFBP‐3 present ex vivo were 11.3 and 78.7 ng/gm of cartilage in normal cartilage and 21.6 and 225.4 ng/gm in OA cartilage.ConclusionThe results show that while IGFBP‐3 is synthesized in explant cultures, IGF‐1 is not. The rate of IGFBP‐3 synthesis is 3 times higher in OA than in normal cartilage. Both IGFBP‐3 and IGF‐1 penetrate into cartilage from SF in vivo. We estimate that the quantities of IGFBP‐3 produced in culture by human cartilage are small compared with the amount supplied in the form of “small complexes” from the circulation. The high value of the partition coefficient of IGFBP‐3 implies binding to the matrix.
Identification and characterization of SmD183–119‐reactive T cells that provide T cell help for pathogenic anti–double‐stranded DNA antibodies
Authors: Riemekasten Gabriela , Langnickel Dirk , Ebling Fanny M. , Karpouzas George , Kalsi Jatinderpal , Herberth Gunda , Tsao Betty P. , Henklein Peter , Langer Sven , Burmester Gerd‐R. , Radbruch Andreas , Hiepe Falk , Hahn Bevra H. 
Published: February 2003

AbstractObjectiveThe C‐terminal peptide of amino acids 83–119 of the SmD1 protein is a target of the autoimmune response in human and murine lupus. This study was undertaken to test the hypothesis that SmD183–119‐reactive T cells play a crucial role in the generation of pathogenic anti–double‐stranded DNA (anti‐dsDNA) antibodies.MethodsSplenic or lymph node T cells derived from unmanipulated as well as SmD183–119‐immunized NZB/NZW mice were analyzed in vitro by enzyme‐linked immunospot (ELISpot) assay to determine T cell help for anti‐dsDNA generation induced by the SmD183–119 peptide. Cytokines expressed by these T cells were measured by ELISpot assay, enzyme‐linked immunosorbent assay, and flow cytometry. SmD183–119‐ and ovalbumin‐specific T cell lines were generated and characterized.ResultsThe SmD183–119 peptide, but not the control peptides, significantly increased the in vitro generation of anti‐dsDNA antibodies in cultures from unmanipulated NZB/NZW mice. Interferon‐γ (IFNγ), interleukin‐2 (IL‐2), IL‐4, transforming growth factor β, and IL‐10 production increased in response to the peptide in young mice; only IFNγ and IL‐2 were increased in older, diseased mice. Activation of SmD183–119‐reactive T cells by immunization of NZB/NZW mice resulted in elevated anti‐dsDNA synthesis and, later, increased antibodies to SmD183–119. Most cells in SmD183–119‐specific CD4+ T cell lines helping both antibodies had increased intracellular expression of IFNγ, and most expressed both IFNγ and IL‐4.ConclusionThe SmD183–119 peptide plays an important role in generating T cell help for autoantibodies, including anti‐dsDNA, and activates different subsets of T cells as defined by distinct cytokine expression. This peptide is an interesting target structure for the modulation of autoreactive T cells, and its characterization may contribute to our understanding of the role of autoantigen‐reactive T cells in the pathogenesis of SLE.
LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: Results from a randomized, double‐blind, placebo‐controlled study
Authors: Alarcón‐Segovia Donato , Tumlin James A. , Furie Richard A. , McKay James D. , Cardiel Mario H. , Strand Vibeke , Bagin Robert G. , Linnik Matthew D. , Hepburn Bonnie ,   LJP 394 Investigator Consortium
Published: February 2003

AbstractObjectiveTo determine whether LJP 394 delays or prevents renal flare in patients with systemic lupus erythematosus (SLE) and a history of renal disease.MethodsIn a 76‐week, double‐blind, placebo‐controlled study, 230 SLE patients were randomized to receive 16 weekly doses of 100 mg of LJP 394 or placebo, followed by alternating 8‐week drug holidays and 12 weekly doses of 50 mg of LJP 394 or placebo. An assay measuring the affinity of the serum IgG fraction for the DNA epitope of LJP 394 identified a high‐affinity population of patients (189 of 213 patients; 89% taking LJP 394 and 90% taking placebo). Analyses were performed on both the intent‐to‐treat population and the high‐affinity population.ResultsAnti–double‐stranded DNA antibodies decreased and C3 levels tended to increase during treatment with LJP 394. In the intent‐to‐treat population, the time to renal flare was not significantly different between treatment groups, but patients taking LJP 394 had a longer time to institution of high‐dose corticosteroids and/or cyclophosphamide (HDCC) and required 41% fewer treatments with HDCC. In the high‐affinity population, the LJP 394 group experienced a longer time to renal flare, 67% fewer renal flares, longer time to institution of HDCC, and 62% fewer HDCC treatments compared with the placebo group. In patients with serum creatinine levels ≥1.5 mg/dl at study entry, those taking LJP 394 had 50% fewer renal flares; no renal flares were observed in the high‐affinity group taking LJP 394. Serious adverse events were observed in 25 of the 114 LJP 394–treated patients (21.9%) and 34 of the 116 placebo‐treated patients (29.3%).ConclusionTreatment with LJP 394 in patients with high‐affinity antibodies to its DNA epitope prolonged the time to renal flare, decreased the number of renal flares, and required fewer HDCC treatments compared with placebo. The study drug appeared to be well tolerated.
The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus
Authors: Anolik Jennifer H. , Campbell Debbie , Felgar Raymond E. , Young Faith , Sanz Inaki , Rosenblatt Joseph , Looney R. John 
Published: February 2003

AbstractObjectiveDespite wide use of the anti‐CD20 monoclonal antibody rituximab in the treatment of B cell lymphomas, the mechanism by which it causes B cell depletion remains a subject of controversy. As part of an ongoing phase I/II trial of rituximab in the treatment of systemic lupus erythematosus (SLE), we sought to determine whether the effectiveness of B cell depletion was influenced by polymorphisms of Fc receptors (FcR) on effector cells.MethodsDuring rituximab treatment of 12 SLE patients, B cell depletion was monitored as a function of the serum rituximab level and FcγRIIa and FcγRIIIa genotypes at baseline and at 1 month and 2 months after treatment. FcR genotypes were determined by polymerase chain reaction. Serum levels of rituximab were measured by enzyme‐linked immunosorbent assay (ELISA). B lymphocyte percentages were assessed by flow cytometry.ResultsB cell depletion was highly variable in this patient cohort, with B cell percentages at the 1–2‐month posttreatment nadir ranging from undetectable (<0.1 cell/μl) to 16% (∼30 cells/μl) of the total peripheral blood lymphocytes. At 2 months posttreatment, B cell percentages were highly correlated with both the serum rituximab level and the FcγRIIIa genotype (R2 = 0.75, P = 0.002). The FcγRIIIa genotype was a significant independent predictor of the efficacy of B cell depletion (P = 0.019).ConclusionThese results highlight the potential variability of B cell depletion by rituximab in the treatment of autoimmune disease and indicate that Fc receptors are an important determinant of that variability. The findings further suggest the importance of antibody‐dependent cell‐mediated cytotoxicity and/or apoptosis induction via FcγRIIIa‐expressing effector cells in the mechanism of B cell depletion by this widely used monoclonal antibody.
Detection of radiographic joint space narrowing in subjects with knee osteoarthritis: Longitudinal comparison of the metatarsophalangeal and semiflexed anteroposterior views
Authors: Mazzuca Steven A. , Brandt Kenneth D. , Buckwalter Kenneth A. 
Published: February 2003

AbstractObjectiveAlthough recent protocols for standardized knee radiography afford highly reproducible radioanatomic alignment of the joint and measurement of joint space width (JSW) in repeat radiographs acquired on the same day, the sensitivity of these techniques to joint space narrowing (JSN) over time in subjects with knee osteoarthritis (OA) is unknown. The present study was undertaken to compare the metatarsophalangeal (MTP) view and the semiflexed anteroposterior (AP) view with respect to sensitivity to JSN in knee OA.MethodsIn 49 subjects with definite knee OA, 2 MTP radiographs and 1 semiflexed AP radiograph were obtained at baseline. Each examination was repeated 14 months later. In MTP views, minimum JSW and the distance between the anterior and posterior margins of the medial tibial plateau (intermargin distance [IMD], an indicator of parallel alignment of the tibial plateau and the x‐ray beam) were measured with a pair of calipers and a magnifying lens fitted with a graticule. JSW in semiflexed AP views was measured by digital image analysis.ResultsThe mean of within‐knee standard deviations of JSW in the baseline MTP examinations (n = 52 OA knees) was 0.24 mm (coefficient of variation 5.8%). Although IMDs in the 2 baseline MTP views were very highly correlated (+0.88), IMDs in the serial examinations were only moderately correlated (+0.45). Serial MTP views showed a small increase in mean JSW over 14 months that was not significantly greater than zero (mean ± SD +0.09 ± 0.66 mm; P not significant). In contrast, concurrent semiflexed AP examinations showed a marginally significant decrease in mean JSW (−0.09 ± 0.31 mm; P = 0.10).ConclusionThese results demonstrate that evidence of the short‐term reproducibility of a radiographic protocol is an insufficient basis on which to predict the quality of its longitudinal performance.