bluuebunny/crossref_metadata_2025 huggingface dataset:
APERCEPCIÓN DE VALOR Y TONALIDAD AFECTIVA: PROBLEMAS DE LA FENOMENOLOGÍA HUSSERLIANA DE LOS SENTIMIENTOS
Authors: Quepons Ignacio
Published: February 2021

De acuerdo con la fenomenología husserliana la experiencia primordial del valor descansa en vivencias emotivas. Para sostener esta idea Husserl sugiere el paralelismo entre la percepción externa y la percepción de los valores. El objetivo de este trabajo es clarificar tal paralelismo enfatizando un problema particular del análisis husserliano: la tonalidad afectiva del objeto de valor y su relación con la apercepción sentimental involucrada en la experiencia de los valores.According to husserlian phenomenology the primordial experience of value lays in emotive lived-experiences. In order to sustain his Idea Husserl suggest a parallelism between the external perception and the perception of values. The aim of this work is to clarify such parallelism stressing a particular problem of husserlian analysis: the affective tonality of the object of value and its relation to the feeling apperception involved in the experience of values.
Aportaciones de Martha Nussbaum y Amartya Sen a la construcción de una dimensión ética en la relación socioeducativa: una revisión sistemática
Authors: Corbella Molina Laura
Published: February 2021

Uno de los retos que se presenta hoy en la pedagogía social es el desarrollo de una teoría sobre ética aplicada a la educación social. Desde esta premisa, el objetivo de este artículo es analizar algunos fundamentos teóricos, tomados de autores relevantes, que ayuden a fundamentar una dimensión ética que sea aplicable a las prácticas socioeducativas. En este trabajo se analizan algunas de las obras de Amartya Sen y Martha Nussbaum, con relación al enfoque de las capacidades. El proceso de análisis consiste en una revisión de tres obras originales y una revisión sistemática de otros autores que han abordado su teoría en el campo de la ética y la educación. El análisis se ha realizado a través de un proceso de codificación inductivo realizado con el software Atlas.ti. Los resultados apuntan elementos de interés para establecer principios socioeducativos basados en el desarrollo integral, la agencia, la participación, la diversidad y la libertad como ejes básicos para asegurar una relación socioeducativa ética acorde con la dignidad humana.
Children’s perceptions about contact and subjective well-being in residential and foster care
Authors: Carvalho João M. S. , Delgado Paulo
Published: February 2021

Contact between children in foster and residential care and their birth families have an impact on children’s development and on placement stability. Contact is also important for their social relationships and sense of belonging and well-being. The aim of this study was, from children’s point of view, to describe, analyse and compare contact in residential care and foster care in terms of its frequency, visit location, feelings during and after the visits, visit difficulties, happiness with their placement, their self-confidence, future perception about their lives, and perception of their subjective well-being. We used a sample of 145 children in residential care and all the children in foster care (39), aged between 11 and 15, from the same four Portuguese districts. Results indicated that children in residential care had more contact and visits with their parents than children in foster care, being phone calls the most used way to contact the children. The majority of the children presented joy or satisfaction during parents’ visits and more diffuse feelings after the visit. Also, most of children would like to have more visits and just a minority present some difficulties in their fulfilment. Nevertheless, children in foster care had more self-confidence, optimism in relation to their future, happiness in relation to their placement and higher subjective well-being than children in residential care. In summary, it seemed that the type of placement for children at risk is more important to their future than the existence of contact with their parents.
Estudio exploratorio sobre las tendencias de la práctica profesional frente a la violencia en entornos de acción socioeducativa
Authors: Ruiz-Galacho Santiago , Martin-Solbes Victor Manuel
Published: February 2021

Introducción: Se expone el papel central de la educación social como disciplina que ofrece una acción bidireccional y de mediación entre las estructuras sociales, de las que emanan diversas formas de violencia estructural, y la ciudadanía, que se ve violentada. Se expresa la diferencia entre formas de violencia objetiva y subjetiva y cómo la cultura de paz ofrece un marco de análisis útil para pensar, desde ella, la práctica socioeducativa. Metodología: A través del uso de entrevistas se han recogido los procesos de significación de la violencia de un grupo de veinticinco profesionales. Son analizadas, haciendo uso de la metodología de la grounded theory, utilizando el software Atlas.ti con un sistema de codificación in vivo. Resultados: Se exponen, por un lado, los efectos de la violencia vivida y su normalización en la práctica socioeducativa y, por otro, el hallazgo de tres tendencias profesionales: vocacional-afectiva, estructurante-coercitiva y ético-reflexiva, con diferentes efectos sobre las dinámicas del ciclo de la violencia en entornos de acción socioeducativa. Discusión: Se plantea una mejora de la práctica socioeducativa a través del desarrollo de la tendencia profesional ético-reflexiva, frente a las limitaciones manifestadas en las otras dos tendencias.
Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism
Authors: Faber Chelsea L , Deem Jennifer D , Phan Bao Anh , Doan Tammy P , Ogimoto Kayoko , Mirzadeh Zaman , Schwartz Michael W , Morton Gregory J
Published: February 2021

The brain plays an essential role in driving daily rhythms of behavior and metabolism in harmony with environmental light–dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative circadian control of feeding and energy homeostasis, but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing (DMHLepR) neurons in this integrative control. Using a viral approach, we show that silencing neurotransmission in DMHLepR neurons in adult mice not only increases body weight and adiposity but also phase-advances diurnal rhythms of feeding and metabolism into the light cycle and abolishes the normal increase in dark-cycle locomotor activity characteristic of nocturnal rodents. Finally, DMHLepR-silenced mice fail to entrain to a restrictive change in food availability. Together, these findings identify DMHLepR neurons as critical determinants of the daily time of feeding and associated metabolic rhythms.
Intestinal fatty acid-binding protein, a biomarker of intestinal barrier dysfunction, increases with the progression of type 2 diabetes
Authors: Wang Yifeng , Ding Licheng , Yang Jiayue , Liu Lijun , Dong Liang
Published: February 2021

Objective

To investigate serum intestinal fatty acid-binding protein (I-FABP) in two groups of patients with different duration of hyperglycemia in a cross-sectional study.

Materials and Methods

In the present study, a total of 280 individuals (158 outpatients and 122 inpatients) suffering from hyperglycemia were recruited between May and September 2019. The clinical information of all participants was collected from the hospital information system, including the duration of hyperglycemia, age, gender, hemoglobin A1c (HbA1c), 75-g oral glucose tolerance test including fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting C-peptide (FC-pep), 2-hour C-peptide (2hC-pep), fasting insulin (FIns), and 2-hour insulin (2hIns). In addition, the morbidity of diabetic complications (retinopathy, neuropathy, and nephropathy) in the inpatient group was determined. Furthermore, the difference between 2hPG and FPG (ΔPG), the difference between 2hC-pep and FC-pep (ΔC-pep), and the difference between 2hIns and FIns (ΔIns) were calculated. The level of serum I-FABP, a biomarker of intestinal barrier (IB) dysfunction, was estimated by an enzyme-linked immunosorbent assay.

Results

For the outpatient group, the median duration of hyperglycemia was less than a year; the serum I-FABP level was positively correlated with age (R = 0.299,P < 0.001). For the inpatient group, the median duration of hyperglycemia was ten years; correlation analysis showed that the serum I-FABP level was positively associated with age and ΔPG (R = 0.286, P = 0.001; R = 0.250, P = 0.006, respectively) while negatively associated with FC-pep and 2hC-pep (R =  − 0.304, P = 0.001; R =  − 0.241, P = 0.008, respectively); multiple linear regression analysis showed that the serum I-FABP level was positively associated with the duration of hyperglycemia (β = 0.362,P < 0.001); moreover, patients with retinopathy had a significantly higher I-FABP level than those without retinopathy (P = 0.001).

Conclusions

In the outpatients whose duration of hyperglycemia was less than a year, the serum I-FABP level was positively associated with age. In the inpatients with different courses of diabetes, the serum I-FABP level was positively associated with the duration of hyperglycemia and glycemic variability but negatively associated with islet beta-cell function; moreover, the serum I-FABP level was higher in patients with retinopathy than in those without retinopathy, suggesting that the IB dysfunction got worse with the progression of diabetes.
Comparison of physical fitness and mental health status among school-age children with different sport-specific training frequencies
Authors: Jiang Ruichen , Xie Chun , Shi Jilong , Mao Xuechen , Huang Qin , Meng Fanying , Ji Zhiguang , Li Anmin , Zhang Chunhua
Published: February 2021

This cross-sectional study compared the physical fitness and mental health status of 140 school-age children who participated in sport-specific training with 180 age-matched peers. All the participants were grouped by sport-specific training frequencies in extracurricular time into the following: (i) high sports training frequency group (HFG): training three to five times per week (n = 77, mean [SD] age: 9.60 [0.12] years); (ii) low sports training frequency group (LFG): training once per week (n = 63, mean [SD] age: 9.88 [0.14] years); and (iii) control group (CG): maintaining routine life (n = 180, mean (SD) age: 9.77(0.09) years). Physical fitness status, including body composition (body mass index), endurance (vital capacity; 50 × 8 round trip), speed and agility (50 m sprint), flexibility (sit-and-reach), coordination (1-min rope skipping), and core strength (1-min sit-ups) as well as mental health status was measured. Overall, the results showed that Grade 3 to 4 HFG students showed better total physical fitness scores than the LFG and CG students. Grade 2 and 5 participants in the three groups showed no significant difference in the total physical fitness score. Children in HFG performed better in several PF indicators (i.e., cardiopulmonary function, flexibility, core strength, and coordination) than those in LFG and CG, and children in LFG got a higher score than those in CG on a testing item of 1-min rope skipping. The mental health test results showed that HFG performed better than LFG and CG. The results indicated that participating in sport-specific training 3–5 times per week was beneficial for children’s physical and mental health. Additionally, there was a weak and negative correlation between physical fitness and mental health in LFG and CG, while no correlation was found between physical fitness and mental health in HFG.
Sistem Pengaman Sepeda Motor Anti Begal
Authors: Dewanto Joni , Tanuwijaya Felix
Published: February 2021

Saat ini marak terjadi pembegalan sepeda motor yang dilakukan tidak hanya dengan mengancam, tetapi juga melukai bahkan membuat korban begal tidak berdaya. Oleh karena itu perlu pengaman tambahan pada sepeda motor yang dapat menggagalkan aksi begal tersebut. Paper ini memaparkan sistem pengaman anti begal dengan memanfaatkan sinyal bluetooth. Sinyal tersebut digunakan sebagai media penghubung untuk mengaktifkan sistem pengaman yang dipasang pada sepeda motor dengan handphone korban. Sistem pengaman yang dirancang berupa alarm dan sistem mematikan mesin sepeda motor. Pada saat terjadi begal sistem bekerja secara otomatis, yaitu ketika jarak antara korban dan sepeda motor lebih besar dari 10 m. Dengan demikian sepeda motor tidak dapat dibawa begal. Bunyi alarm diharapkan akan menarik perhatian masyarakat untuk datang membantu korban. Sedang pada saat ditinggal di tempat parkir, sistem ini sekaligus juga dimanfaatkan sebagai sistem pengaman tambahan yang bekerja secara  elektronik.  Sistem pengaman ini dirancang menggunakan perangkat pengatur  Arduino pro mikro dengan bahasa pemrograman C ++ yang telah disederhanakan. Rancangan sistem pengaman ini sudah diimlementasikan di sepeda motor Honda Blade Repsol tahun 2012, dan dilakukan uji fungsi serta keandalan sistem. Hasil pengujian menunjukkan bahwa sistem dapat bekerja dengan baik dan memiliki keandalan  yang tinggi.
Perancangan dan Pengujian Lensa Fresnel pada Kolektor Surya Plat Datar
Authors: Anggraini Handoyo Ekadewi , Bisono Indriati Njoto , Jonathan Peter
Published: February 2021

Energi matahari dapat dikonversikan menjadi energi termal dengan menggunakan kolektor surya maupun menjadi energi listrik dengan menggunakan sel surya/photovoltaic. Radiasi matahari bersifat menyebar, sehingga memerlukan pengumpul atau pengarah agar lebih fokus.Ada banyak penelitian yang menggunakan lensa Fresnel untuk mengumpulkan radiasi matahari pada sel surya. Sedang penelitian lensa Fresnel pada kolektor surya masih terbatas sebagai concentrator. Makalah ini membahas perancangan dan pemakaian lensa Fresnel sebagai penutup pada suatu kolektor surya plat datar. Lensa Fresnel komersial hanya memiliki 1 titik fokus, maka langkah pertama penelitian adalah merancang lensa Fresnel dengan enam titik fokus. Jarak focus dirancang agar radiasi matahari jatuh ke plat penyerap pada jarak 90 mm dari lensa Fresnel. Bahan yang digunakan adalah PMMA Polymethyl methacrylate (acrylic) dan pembuatan profil lensa menggunakan proses tekan. Lensa Fresnel yang dihasilkan berhasil memiliki titik fokus 90 mm. Lensa Fresnel yang dihasilkan dipasang sebagai penutup pada kolektor surya plat datar. Hasil yang didapat adalah temperatur plat penyerap dengan lensa Fresnel lebih tinggi daripada dengan acrylic polos yang sebenarnya lebih bening. Temperatur maksimum di kiri atas plat penyerap dengan lensa Fresnel dapat mencapai 1.42 kali lebih tinggidaripada temperatur yang dihasilkan oleh acrylic polos. Temperatur cairan di inlet dan dalam tangki pada kolektor surya yang menggunakan lensa Fresnel lebih tinggi daripada temperatur cairan di kedua lokasi yang sama yang menggunakan acrylic polos.
Biological properties of griseolic acid, a cyclic AMP phosphodiesterase inhibitor with an adenine group
Authors: Iijima Yasuteru , Nakagawa Fumio , Handa Shuji , Oda Tomiichiro , Naito Atsushi , Yamazaki Mitsuo
Published: July 2002

Griseolic acid inhibited cAMP phosphodiesterase (PDE) at low concentrations, the I
50 being of the order of 0.01–0.1 μM. Administration of griseolic acid to rats increased the cAMP level in liver and plasma several‐fold. It increased glycogen degradation in mouse liver and stimulated lipolysis in isolated rat fat cells. Griseolic acid did not block the adenosine‐elicited accumulation of cAMP in guinea pig brain slices. It had no effect on cAMP‐dependent protein kinase from rat liver nor on the adenyl cyclase from rat brain.
Modified forms of vasopressin and oxytocin in a bovine pineal preparation
Authors: Noteborn H.P.J.M. , Burbach J.P.H. , Ebels I.
Published: July 2002

A bovine pineal acid extract displays a vasotocin‐like bioactivity in several bioassays, and is recognized by antibodies against the Pro‐Arg‐Gly‐amide ending common to vasopressin and vasotocin. By using molecular sieve filtration and reversed‐phase HPLC, a vasopressin‐ and oxytocin‐like peptide was isolated from this pineal preparation, while no evidence for a vasotocin‐like peptide was obtained. The isolated neuropeptides contain a modified amino acid at position 2. This structural difference with authentic pituitary vasopressin and oxytocin may alter their biological and immunological properties, which have been interpreted as vasotocin‐like, and thus underlies the controversy concerning the existence of vasotocin in the mammalian pineal gland.
Effect of proteinase inhibitors on intracellular processing of cathepsin B, H and L in rat macrophages
Authors: Hara Kenji , Kominami Eiki , Katunuma Nobuhiko
Published: July 2002

The effects of various proteinase inhibitors on the processing of lysosomal cathepsins B, H and L were investigated in cultured rat peritoneal macrophages. The processing of newly synthesized pro‐cathepsins B, H and L to the mature single‐chain enzymes was sensitive to a metal chelator,1,10‐phenanthroline, and a synthetic metalloendopeptidase substrate, Z‐Gly‐Leu‐NH2, and insensitive to inhibitors of serine proteinases, aspartic proteinases and cysteine proteinases. Inhibitors of cysteine proteinases, E‐64‐d and leupeptin, inhibited the processing of the single‐chain forms of cathepsins B, H and L to the two‐chain forms. These results suggest that (a) metal endopeptidase(s) is (are) involved in the propeptide processing of cathepsin B, H and L, and that proteolytic cleavages of the mature single‐chain cathepsins are accomplished by cysteine proteinases in lysosomes.
The complete amino acid sequence of bovine milk angiogenin
Authors: Maes P. , Damart D. , Rommens C. , Montreuil J. , Spik G. , Tartar A.
Published: July 2002

The amino acid sequence of angiogenin isolated from bovine milk was deduced by gas‐phase sequencing of the protein and its fragments. The protein contains 125 residues and has a calculated molecular mass of 14 577 Da. The sequence is highly homologous (65% identity) to the sequence of human angiogenin, most of the differences being the result of conservative replacements. Like human angiogenin, the bovine protein is also homologous to bovine pancreatic RNase A (34% identity) and the three major active site residues known to be involved in the catalytic process, His‐14, Lys‐41 and His‐115, are conserved. When tested against conventional substrates for RNase A activity, bovine angiogenin displays the same selective ribonucleolytic activity as human angiogenin. The sequence of bovine angiogenin contains the cell recognition tripeptide Arg‐Gly‐Asp which is not present in the human protein.
Identification and signal transduction mechanism of elastin peptide receptor in human leukocytes
Authors: Varga Z. , Jacob M.P. , Robert L. , Fülöp T.
Published: July 2002

The existence of a novel receptor on human polymorphonuclear leukocytes (PMNLs) and monocytes was demonstrated, named soluble elastin peptide receptor. Soluble elastin peptides, like K‐elastin, which are liberated from elastin fibres, can be found in the sera, and they possess several biological activities such as chemotaxis. Studying the effects of elastin peptides on leukocytes, it was found that: (i) the elastin peptide stimulates the oxidative burst, the intracellular free Ca2+ elevation through a specific receptor; and (ii) in the signal transduction mechanism of this elastin peptide receptor, the phosphatidylinositol breakdown is involved.
Intraspecific myosin light chain polymorphism in the white muscle of herring (Clupea harengus harengus, L.)
Authors: Martinez I. , Ofstad R. , Olsen R.L.
Published: July 2002

The myosin contained in white and red muscles of herring (Clupea harengus harengus) was purified, and its subunit composition analyzed by electrophoretic techniques. The only myosin isoform present in red muscles was made up of one type of heavy chain and two types of light chain. The native myosin from white muscles migrated as one wide band. Analysis of the extracts by SDS/glycerol/PAGE from white muscles revealed one main type of heavy chain. Light chains were identified by SDS‐PAGE analysis of electrophoretically purified myosin, and two‐dimensional electrophoresis of the extracts demonstrated differences in the light chain composition of white and red muscles. Using this methodology, light chain polymorphism was detected in white muscles among members of the same species.
Iron overload and gene expression in HepG2 cells: analysis by differential display
Authors: Barisani Donatella , Meneveri Raffaella , Ginelli Enrico , Cassani Camilla , Conte Dario
Published: July 2002

The aim of the present study was to evaluate the effect of iron overload on gene expression in HepG2 cells by differential display. Iron‐treated cells showed a 50% decrease in apolipoprotein B100 (Apo B100) and a 2‐ and 3‐fold increase in semaphorin cd100 and aldose reductase mRNA, respectively, with parallel variations in Apo B100 and aldose reductase proteins. These effects were time‐dependent. Vitamin E prevented the increase in aldose reductase expression, but had no effect on Apo B100 and semaphorin cd100. Treatment with hydrogen peroxide and 4‐hydroxy‐2,3‐nonenal increased only aldose reductase mRNA. These data suggest that iron can affect mRNA levels by lipid peroxidation‐dependent and ‐independent pathways.
Biophysical characterization of SipA, an actin‐binding protein from Salmonella enterica
Authors: Mitra Kakoli , Zhou Daoguo , Galán Jorge E.
Published: July 2002

An essential step in the pathogenesis of Salmonella enterica infections is bacterial entry into non‐phagocytic cells of the intestinal epithelium. Proteins injected by Salmonella into host cells stimulate cellular responses that lead to extensive actin cytoskeleton reorganization and subsequent bacterial uptake. One of these proteins, SipA, modulates actin dynamics by directly binding to F‐actin. We have biophysically characterized a C‐terminal fragment, SipA446–684, which has previously been shown to retain activity. Our results show that SipA446–684 exhibits an elongated shape with a predominantly helical conformation and predict the existence of a coiled‐coil domain. We suggest that the protein is able to span two adjacent actin monomers in a filament and propose a model that is consistent with the observed effects of SipA446–684 on actin dynamics and F‐actin stability and morphology.
Isotope dilution GC/MS determination of anandamide and other fatty acylethanolamides in rat blood plasma
Authors: Giuffrida Andrea , Piomelli Daniele
Published: July 2002

Anandamide and allied fatty acylethanolamides (AEs) may act as signalling molecules in brain and peripheral tissues. In the present study, we describe an electron‐impact gas chromatography/mass spectrometry (GC/MS) method based on isotope dilution, which may be used for the identification and quantification of anandamide and other AEs in biological matrices. The calibration curves for standard AEs were linear over the range 0–1000 pmol (r
2=0.99) with a coefficient of variation of 4% at 2.5 pmol. Detection and quantification limits were in the high fmol to low pmol range for all AEs. Using this method we measured nanomolar concentrations of three endogenous AEs in deproteinated rat blood plasma (anandamide: 5.2 pmol/ml; palmitylethanolamide: 16.7 pmol/ml; oleylethanolamide: 8.1 pmol/ml). These results are consistent with a regulatory role of anandamide and other AEs in peripheral tissues.
Phosphorylation of ATPase subunits of the 26S proteasome
Authors: Mason Grant G.F. , Murray Rachael Z. , Pappin Daryl , Rivett A.Jennifer
Published: July 2002

The 26S proteasome complex plays a major role in the non‐lysosomal degradation of intracellular proteins. Purified 26S proteasomes give a pattern of more than 40 spots on 2D‐PAGE gels. The positions of subunits have been identified by mass spectrometry of tryptic peptides and by immunoblotting with subunit‐specific antipeptide antibodies. Two‐dimensional polyacrylamide gel electrophoresis of proteasomes immunoprecipitated from [32P]phosphate‐labelled human embryo lung L‐132 cells revealed the presence of at least three major phosphorylated polypeptides among the regulatory subunits as well as the C8 and C9 components of the core 20S proteasome. Comparison with the positions of the regulatory polypeptides revealed a minor phosphorylated form to be S7 (MSS1). Antibodies against S4, S6 (TBP7) and S12 (MOV34) all cross‐reacted at the position of major phosphorylated polypeptides suggesting that several of the ATPase subunits may be phosphorylated. The phosphorylation of S4 was confirmed by double immunoprecipitation experiments in which 26S proteasomes were immunoprecipitated as above and dissociated and then S4 was immunoprecipitated with subunit‐specific antibodies. Antibodies against the non‐ATPase subunit S10, which has been suggested by others to be phosphorylated, did not coincide with the position of a phosphorylated polypeptide. Some differences were observed in the 2D‐PAGE pattern of proteasomes immunoprecipitated from cultured cells compared to purified rat liver 26S proteasomes suggesting possible differences in subunit compositions of 26S proteasomes.
Purification of protein phosphatase 4 catalytic subunit: inhibition by the antitumour drug fostriecin and other tumour suppressors and promoters
Authors: Hastie C.James , Cohen Patricia T.W
Published: July 2002

Protein phosphatase 4 (PP4) is a protein serine/threonine phosphatase that predominantly localises to centrosomes and plays a role in microtubule organisation at centrosomes. Here, PP4 catalytic subunit has been purified from porcine testis to near homogeneity and a specific activity of 680 mU/mg against phosphorylase a. The antitumour drug, fostriecin, inhibits PP4 catalytic subunit (IC50 3 nM) with similar potency to PP2A catalytic subunit (IC50 1.5 nM). PP4 is also inhibited in the nanomolar range by several naturally occurring tumour promoters and toxins, with similar IC50 values to those obtained for PP2A. The gene for human PP4 catalytic subunit localises to 16p11.2.
Dual effects of suppressor of cytokine signaling (SOCS‐2) on growth hormone signal transduction
Authors: Favre Hélène , Benhamou Aurélie , Finidori Joelle , Kelly Paul A. , Edery Marc
Published: July 2002

A family of suppressors of cytokine signaling (SOCS) has recently been identified of which two members have been shown to block growth hormone (GH) signaling. Dose‐response experiments were conducted in 293 cells and SOCS‐1 and SOCS‐3 were shown to inhibit the transcriptional activation of a GH‐responsive element and suppressed Jak2 tyrosine kinase activity. SOCS‐2 had two opposite effects: at low concentrations it inhibited GH‐induced STAT5‐dependent gene transcription, but restoration of GH signaling was observed at higher concentrations. In cotransfection studies, SOCS‐2 was able to block the inhibitory effect of SOCS‐1 but not that of SOCS‐3 on GH signaling. These findings suggest that a major function for SOCS‐2 is to restore the sensitivity to GH by overcoming the initial inhibitory effects of other endogenous SOCS molecules.
Peroxynitrite generated from constitutive nitric oxide synthase mediates the early biochemical injury in short‐term cultured hepatocytes
Authors: López-Garcı́a M.Pilar , Sanz-González Silvia M
Published: July 2002

Early loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study provides experimental evidence for the induction – shortly after isolation through the classical procedure – of strong oxidative stress that involves both oxygen‐derived and NO‐derived species. NO formation at this stage is due to the early activation of liver constitutive NO synthase (cNOS). Immunodetection of nitrated proteins provides direct evidence of endogenous peroxynitrite (PN) formation upon hepatocyte isolation. On the basis of the combined use of dihydrorhodamine 123 and NOS inhibitors, the analysis of the amount, time course and nature of the species involved supports the view that PN generated from cNOS‐derived NO, while not affecting cell viability and hepatocyte monolayer development, is the main species likely responsible for the early biochemical injury commonly observed in hepatocyte cultures.
The effect of dynamic compression on the response of articular cartilage to insulin‐like growth factor‐I
Authors: Bonassar Lawrence J. , Grodzinsky Alan J. , Frank Eliot H. , Davila Salomon G. , Bhaktav Nirav R. , Trippel Stephen B.
Published: July 2002

Articular cartilage is routinely subjected to mechanical forces and to cell‐regulatory molecules. Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal, dynamic compression and insulin‐like growth factor‐I (IGF‐I), a polypeptide in synovial fluid that is anabolic for cartilage. In bovine patellofemoral cartilage explants, IGF‐I increased protein and proteoglycan synthesis 90% and 120%, respectively while dynamic compression increased protein and proteoglycan synthesis 40% and 90%, respectively. Stimulation by IGF‐I was significantly greater than by dynamic compression for both protein and proteoglycan synthesis. When applied together, the two stimuli enhanced protein and proteoglycan synthesis by 180% and 290%, respectively, a degree greater than that achieved by either stimulus alone. IGF‐I augmented protein synthesis with a time constant of 12.2 h. Dynamic compression increased protein synthesis with a time constant of 2.9 h, a rate significantly faster than that of IGF‐I, suggesting that these signals act via distinct cell activation pathways. When used together, dynamic compression and IGF‐I acted with a time constant of 5.6 h. Thus, dynamic compression accelerated the biosynthetic response to IGF‐I and increased transport of IGF‐I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Molecular aspects of healing in stabilized and non‐stabilized fractures
Authors: Le A. X. , Miclau T. , Hu D. , Helms J. A.
Published: July 2002

Bone formation is a continuous process that is initiated during fetal development and persists in adults in the form of bone regeneration and remodeling. These latter two aspects of bone formation are clearly influenced by the mechanical environment. In this study we tested the hypothesis that alterations in the mechanical environment regulate the program of mesenchymal cell differentiation, and thus the formation of a cartilage or bony callus, at the site of injury. As a first step in testing this hypothesis we produced stabilized and non‐stabilized tibial fractures in a mouse model, then used molecular and cellular methods to examine the stage of healing. Using the “molecular map” of the fracture callus, we divided our analyzes into three phases of fracture healing: the inflammatory or initial phase of healing, the soft callus or intermediate stage, and the hard callus stage. Our results show that indian hedgehog(ihh), which regulates aspects of chondrocyte maturation during fetal and early postnatal skeletogenesis, was expressed earlier in an non‐stabilized fracture callus as compared to a stabilized callus, ihh persisted in the non‐stabilized fracture whereas its expression was down‐regulated in the stabilized bone. IHH exerts its effects on chondrocyte maturation through a feedback loop that may involve bone morphogenetic protein 6 [bmp6; (S. Pathi, J.B. Rutenberg, R.L. Johnson, A. Vortkamp, Developmental Biology 209 (1999) 239–253)] and the transcription factor gli3, bmp6 and gli3 were re‐induced in domain adjacent to the ihh‐positive cells during the soft and hard callus stages of healing. Thus, stabilizing the fracture, which circumvents or decreases the cartilaginous phase of bone repair, correlates with a decrease in ihh signaling in the fracture callus. Collectively, our results illustrate that the ihh signaling pathway participates in fracture repair, and that the mechanical environment affects the temporal induction of ihh, bmp6 and gli3. These data support the hypothesis that mechanical influences affect mesenchymal cell differentiation to bone. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging‐detected bone bruises after acute anterior cruciate ligament tears
Authors: Fang Carrie , Johnson Darren , Leslie Michael P. , Carlson Cathy S. , Robbins Matthew , Cesare Paul E. Di
Published: July 2002

Histologic and immunostaining analyses were performed on articular cartilage/subchondral bone biopsy specimens overlying MRI‐detected bone bruises in 12 patients with anterior cruciate ligament (ACL) tears. Staining with toluidine blue for proteoglycan revealed loss of staining from the superficial portion of the articular cartilage. Immunostaining for cartilage oligomeric matrix protein (COMP) showed an increased staining in the superficial matrix of the articular cartilage. Using polyclonal antisera against COMP, the authors performed a competitive enzyme‐linked immunosorbent assay (ELISA) on the synovial fluid from the injured and uninjured knees. There was an approximately 10‐fold higher synovial fluid COMP levels in injured knees. The COMP levels were greater in those patients who had synovial fluid samples harvested closer to the date of initial injury. Western blot analysis of the synovial fluid showed an increased presence of COMP degradation fragments from injured knees. These results are indicative of a significant injury to the articular cartilage, and may represent preclinical posttraumatic osteoarthritic lesions. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The enhancement of periosteal chondrogenesis in organ culture by dynamic fluid pressure
Authors: Mukherjee Niley , Saris Daniel B. F. , Schultz Fredrick M. , Berglund Lawrence J. , An Kai N. , O'Driscoll Shawn W.
Published: July 2002

Cartilage repair by autologous periosteal arthroplasty is enhanced by continuous passive motion (CPM) of the joint after transplantation of the periosteal graft. However, the mechanisms by which CPM stimulate chondrogenesis are unknown. Based on the observation that an oscillating intra‐synovial pressure fluctuation has been reported to occur during CPM (0.6–10 kPa), it was hypothesized that the oscillating pressure experienced by the periosteal graft as a result of CPM has a beneficial effect on the chondrogenic response of the graft. We have developed an in vitro model with which dynamic fluid pressures (DFP) that mimic those during CPM can be applied to periosteal explants while they are cultured in agarose gel suspension. In this study periosteal explants were treated with or without DFP during suspension culture in agarose, which is conducive to chondrogenesis. Different DFP application times (30 min, 4 h, 24 h/day) and pressure magnitudes (13, 103 kPa or stepwise 13 to 54 to 103 kPa) were compared for their effects on periosteal chondrogenesis. Low levels of DFP (13 kPa at 0.3 Hz) significantly enhanced chondrogenesis over controls (34 ± 7% vs 14 ± 5%; P < 0.05), while higher pressures (103 kPa at 0.3 Hz) completely inhibited chondrogenesis, as determined from the percentage of tissue that was determined to be cartilage by histomorphometry. Application of low levels of DFP to periosteal explants also resulted in significantly increased concentrations of Collagen Type II protein (43 ± 8% vs 10 ± 5%; P < 0.05). New proteoglycan synthesis, as measured by 35S‐sulphate uptake was increased by 30% in periosteal explants stimulated with DFP (350 ± 50 DPM vs 250 ± 75 DPM of 35S‐sulphate uptake/μg total protein), when compared to controls though this difference was not statistically significant. The DFP effect at low levels was dose‐dependant for time of application as well, with 4 h/day stimulation causing significantly higher chondrogenesis than just 30 min/day (34 ± 7 vs 12 ± 4% cartilage; P < 0.05) and not significantly less than that obtained with 24 h/day of DFP (48 ± 9% cartilage, P < 0.05). These observations may partially explain the beneficial effect on cartilage repair by CPM. They also validate an in vitro model permitting studies aimed at elucidating the mechanisms of action of mechanical factors regulating chondrogenesis. The fact that these tissues were successfully cultured in a mechanical environment for six weeks makes it possible to study the actions of mechanical factors on the entire chondrogenic pathway, from induction to maturation. Finally, these data support the theoretical predictions regarding the role of hydrostatic compression in fracture healing. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Signal transduction pathways and apoptosis in bacteria infected chondrocytes
Authors: Lee Mel S. , Yen Chen‐Yu , Ueng Steve W. N. , Shih Chun‐Hsiung , Chao Chuck C. K.
Published: July 2002

The mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un‐infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05). Signal transduction pathways activated by bacterial infection were assessed by co‐transfection technique. After infection, the c‐Jun N‐terminal kinase, extracellular signal‐regulated kinase, and cyclic AMP‐dependent protein kinase activities were elevated by 7.6‐, 7.3‐, and 3.2‐fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post‐infectious destructive arthropathy. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Insulin‐like growth factor‐I gene expression patterns during spontaneous repair of acute articular cartilage injury
Authors: Fortier Lisa A. , Balkman Cheryl E. , Sandell Linda J. , Ratcliffe Anthony , Nixon Alan J.
Published: July 2002

This study evaluated the constitutive insulin‐like growth factor‐I (IGF‐I) gene expression pattern in spontaneously healing cartilage defects over the course of 16 weeks, and correlated the tissue morphology and matrix gene expression with IGF‐I mRNA levels. Full‐thickness 15 mm cartilage defects were debrided in the femoral trochlea of both femoropatellar joints of 8 horses and the healing defects examined 2, 4, 8, or 16 weeks after surgery. Samples were harvested for histologic assessment of tissue healing using H&E staining, toluidine blue histochemical reaction for proteogiycan deposition, and in situ hybridization and immunohistochemistry procedures to demonstrate collagen type II mRNA and protein expression. Total RNA was isolated for Northern analysis to measure cartilage matrix molecule expression, and for semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) to determine IGF‐I gene expression patterns in healing cartilage defects. Full‐thickness cartilage defects in horses were slow to heal compared to smaller lesions in similar locations in other animals. However, a progressive decline in tissue cellularity and vascularity, and increased tissue organization were observed on H&E stained specimens over the 16‐week experiment. Evidence of early chondrogenic repair was detected through collagen type II in situ hybridization and immunohistochemistry. However, levels of collagen type II and aggrecan mRNA in lesions were not abundant on Northern analysis indicating incomplete chondrogenesis. IGF‐I message expression followed a cyclic pattern with low levels at 2 weeks, followed by an increase at 4 and 8 weeks, and a subsequent decline at 16 weeks. There was no direct correlation between the stage of healing and cartilage matrix message expression, and the abundance of IGF‐I mRNA in the healing lesions. In conclusion, this study demonstrated that the spontaneous healing of articular defects was accompanied by a temporal fluctuation in IGF‐I gene expression which was discoordinate to the steady rise in expression of cartilage matrix molecules such as procollagen type II. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The effect of NKISK on tendon in an in vivo model
Authors: Caprise Peter A. , Lester Gayle E. , Weinhold Paul , Hill Jeff , Dahners Laurence E.
Published: July 2002

The mechanism through which ligaments and tendons change length during growth and contracture is unclear. It has been hypothesized that there is a reversible “interfibrillar bond” that, when broken, allows the sliding of collagen fibrils past one another during length changes. The pentapeptide NKISK has been reported to inhibit the binding of decorin to fibronectin. This study was designed to evaluate the effect of NKISK in an in vivo model. Male Sprague—Dawley rats were divided into three groups (n=9, 9 and 14, respectively). The left patellar tendon was injected with 1.0 ml of NKISK (Group 1 = 1.0 mM, Groups 2 and 3 = 5.0 mM). The contralateral/control limb was injected with carrier. Group 1 was sacrificed after three. Group 2 after four and Group 3 after seven daily injections. The patellar tendon lengths were measured in all groups with comparisons made to the contralateral control limb. NKISK injection resulted in a significant increase in length in Group 2 (3.14% ± 2.04, P = 0.002) and in Group 3 (6.12% ± 3.84, P < 0.001). Biomechanical testing of Group 3 showed no differences in maximum load, ultimate strength, structural stiffness, or elastic modulus of the treated tendons but did demonstrate a statistically significant decrease in the displacement and strain at maximum load in the NKISK‐treated tendons. This study demonstrates that inhibition of decorin/fibronectin binding by NKISK results in tendon lengthening in an in vivo setting as noted by a progressive increase in the length of the patellar tendon. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.
Autologous chondrocyte implantation in a canine model: change in composition of reparative tissue with time
Authors: Breinan H. A. , Minas T. , Hsu H‐P. , Nehrer S. , Shortkroff S. , Spector M.
Published: July 2002

The objective of the study was to evaluate the tissue types filling 4‐mm diameter defects in the canine trochlear groove 1.5, 3, and 6 months after autologous chondrocyte implantation (ACI). Untreated defects served as controls. Periosteum alone controls were also included at the 1.5‐month time period. The results were compared with previously published findings obtained 12 and 18 months postoperative. After 3 months the ACI‐treated defects contained significantly more reparative tissue than found in the untreated control group, including twice the amount of hyaline cartilage (HC). These findings, however, were the only significant effects of the ACI treatment when compared to the periosteum alone or empty control groups. The benefits of ACI found at 3 months did not persist to longer time periods. An evaluation of the inter‐observer error associated with the histomorphometric method indicated that it was generally less than the inter‐animal variation in the results. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Origin and pathway of sensory nerve fibers to the ventral and dorsal sides of the sacroiliac joint in rats
Authors: Murata Yasuaki , Takahashi Kazuhisa , Masatsune  , Yamagata  , Takahashi Yuzuru , Shimada Yutaka , Moriya Hideshige
Published: July 2002

The purpose of this study is to clarify sensory innervation in the ventral and dorsal sides of the sacroiliac joint. Fluoro‐gold, a neural tracer, was injected into the left sacroiliac joint of adult rats from the dorsal side after denervation of the dorsal side, and the bilateral dorsal root ganglia (DRGs) from T13 to S4 were examined by fluorescence microscopy five days after injection. In another rat group, the DRGs were examined using the same methods after injection of fluoro‐gold from the ventral side. In the case of dorsal denervation (ventral nerve supply), labeled neurons were mainly located in the ipsilateral DRGs from L1 to S2. On the other hand, in the case of ventral denervation (dorsal nerve supply), labeled neurons were noted in the ipsilateral DRGs from L4 to S2. The sacroiliac joint in rats is innervated differently on the ventral and dorsal sides: the sensory nerve fibers to the dorsal side of the sacroiliac joint were derived from the DRGs of lower lumbar and sacral levels (from L4 to S2); and those to the ventral side from the DRGs of upper lumbar, lower lumbar, and sacral levels (from L1 to S2). © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Q‐angle influences tibiofemoral and patellofemoral kinematics
Authors: Mizuno Yasayuki , Kumagai Masaru , Mattessich Stephen M. , Elias John J. , Ramrattan Navin , Cosgarea Andrew J. , Chao Edmund Y. S.
Published: July 2002

Numerous surgical procedures have been developed to correct patellar tracking and improve patellofemoral symptoms by altering the Q‐angle (the angle between the quadriceps load vector and the patellar tendon load vector). The influence of the Q‐angle on knee kinematics has yet to be specifically quantified, however. In vitro knee simulation was performed to relate the Q‐angle to tibiofemoral and patellofemoral kinematics. Six cadaver knees were tested by applying simulated hamstrings, quadriceps and hip loads to induce knee flexion. The knees were tested with a normal alignment, after increasing the Q‐angle and after decreasing the Q‐angle. Increasing the Q‐angle significantly shifted the patella laterally from 20° to 60° of knee flexion, tilted the patella medially from 20° to 80° of flexion, and rotated the patella medially from 20° to 50° of flexion. Decreasing the Q‐angle significantly tilted the patella laterally at 20° and from 50° to 80° of flexion, rotated the tibia externally from 30° to 60° of flexion, and increased the tibiofemoral varus orientation from 40° to 90° of flexion. The results show that an increase in the Q‐angle could lead to lateral patellar dislocation or increased lateral patellofemoral contact pressures. A Q‐angle decrease may not shift the patella medially, but could increase the medial tibiofemoral contact pressure by increasing the varus orientation. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.