bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential involvement of NF-κB and MAP kinase pathways in the generation of inflammatory cytokines by human neutrophils
Authors: Cloutier Alexandre , Ear Thornin , Blais-Charron Emilie , Dubois Claire M , McDonald Patrick P 
Published: October 2006

AbstractThe ability of human neutrophils to express a variety of genes encoding inflammatory mediators is well documented, and mounting evidence suggests that neutrophil-derived cytokines and chemokines contribute to the recruitment of discrete leukocyte populations at inflammatory sites. Despite this, our understanding of the signaling intermediates governing the generation of inflammatory cytokines by neutrophils remains fragmentary. Here, we report that inhibitors of the p38 MAPK and MEK pathways substantially diminish the release of (and in the case of p38 inhibitors, the gene expression of) several inflammatory cytokines in neutrophils stimulated with LPS or TNF. In addition, various NF-κB inhibitors were found to profoundly impede the inducible gene expression and release of inflammatory cytokines in these cells. The MAPK inhibitors did not affect NF-κB activation; instead, the transcriptional effects of the p38 MAPK inhibitor appear to involve transcriptional factor IID. Conversely, the NF-κB inhibitors failed to affect the activation of MAPKs. Finally, the MAPK inhibitors were found to prevent the activation a key component of the translational machinery, S6 ribosomal protein, in keeping with their post-transcriptional impact on cytokine generation. To our knowledge, this constitutes the first demonstration that in neutrophils, the inducible expression of proinflammatory cytokines by physiological stimuli largely reflects the ability of the latter to activate NF-κB and selected MAPK pathways. Our data also raise the possibility that NF-κB or MAPK inhibitors could be useful in the treatment of inflammatory disorders in which neutrophils predominate.
Sex Hormone Status May Modulate Rate of Expansion of Proximal Femur Diameter in Older Women alongside Other Skeletal Regulators
Authors: Kaptoge S. , Dalzell N. , Folkerd E. , Doody D. , Khaw K.-T. , Beck T. J. , Loveridge N. , Mawer E. B. , Berry J. L. , Shearer M. J. , Dowsett M. , Reeve J. 
Published: October 2006

Abstract
Context: Little is known of associations between hip geometry and skeletal regulators. This is important because geometry is a determinant of both hip function and resistance to fracture.
Objective: We aimed to determine the effects of sex hormone status and other candidate regulators on hip geometry and strength.
Subjects and Methods: A random sample of 351 women aged 67–79 had two to four hip dual-energy x-ray absorptiometry scans performed over 8 yr of follow-up. Hip structural analysis software was used to measure subperiosteal diameter (PD) and the distance from the center of mass to the lateral cortical margin (d-lat) on three 5-mm-thick cross-sectional regions: narrow neck, intertrochanter, and shaft. Section modulus (Z), bone mineral density (grams per centimeter squared), and an index of bone mineral content (cross-sectional area) were calculated as estimators of bone strength. Serum analytes measured at baseline included SHBG, estradiol, PTH, creatinine, albumin, vitamin D metabolites, and glutamate- and γ-carboxyglutamate-osteocalcin (OC). A linear mixed model was used to model associations with predictor variables, including testing whether the predictors significantly modified the effect of aging.
Results: Aging was associated with increasing PD and d-lat, and higher baseline SHBG significantly modified this effect, in the case of PD, increasing the rates of change at the narrow neck region by 19% for SHBG level 2 sd higher than population mean (P = 0.026). Higher baseline creatinine was independently associated with faster increases in PD and d-lat with aging (P &lt; 0.041). Z declined faster with aging if baseline PTH was higher, and higher albumin had a contrary effect. Z was positively associated with free estradiol and inversely associated with SHBG and glutamate-OC.
Conclusion: These results show large effects of SHBG on the regulation of proximal femur expansion and bending resistance, probably acting as a surrogate for low bioavailable estrogen. Potentially important effects for fracture resistance in old age were also revealed for PTH, markers related to renal function and the nutritional markers albumin and undercarboxylated OC.
Prevalence of Autoantibody-Negative Diabetes Is Not Rare at All Ages and Increases with Older Age and Obesity
Authors: Wang Jian , Miao Dongmei , Babu Sunanda , Yu Jeesuk , Barker Jennifer , Klingensmith Georgeanna , Rewers Marian , Eisenbarth George S. , Yu Liping 
Published: October 2006

Abstract
Objective: A significant percentage of nonautoimmune forms of diabetes presents among children in all age groups, with a remarkable increase with age.
Design: From October 1992 to October 2004, a total of 859 children less than 18 yr of age were newly diagnosed with diabetes at the Barbara Davis Center for Childhood Diabetes and had blood samples obtained within 2 wk of disease onset for analysis of antiislet autoantibodies to glutamic acid decarboxylase-65, insulinoma-associated antigen-2, insulin, and islet cell autoantibodies. The relationship of autoantibody positivity with human leukocyte antigen (HLA) class II, body mass index (BMI), glycosylated hemoglobin, age, and ethnicity was analyzed.
Results: Overall 19% (159 of 859) of these children with newly diagnosed diabetes were negative for all autoantibodies, and autoantibody negativity was significantly increased with age (P &lt; 0.01). The Hispanic and Black subjects had significantly increased autoantibody negativity among older children with higher BMI than White subjects. The patients with the highest risk HLA genotype, DR3-DQ2/DR4-DQ8, were significantly less autoantibody negative (P = 0.001), whereas the HLA-protective allele, DQB1*0602, was significantly increased among the autoantibody-negative patients (P &lt; 0.0001). Insulin autoantibodies were dramatically age dependent and were inversely correlated with age in both prevalence (P &lt; 0.0001) and levels (P &lt; 0.0001). Autoantibody positivity was inversely correlated with both BMI and age using multivariate analysis (P &lt; 0.0001 and P = 0.0078, respectively).
Conclusions: A significant percentage of children newly diagnosed with diabetes are negative for all antiislet autoantibodies with a marked increase in obesity-associated autoantibody-negative diabetes after age 10, suggesting diabetes heterogeneity at all ages.
High-Fat/Low-Carbohydrate Diet Reduces Insulin-Stimulated Carbohydrate Oxidation but Stimulates Nonoxidative Glucose Disposal in Humans: An Important Role for Skeletal Muscle Pyruvate Dehydrogenase Kinase 4
Authors: Chokkalingam K. , Jewell K. , Norton L. , Littlewood J. , van Loon L. J. C. , Mansell P. , Macdonald I. A. , Tsintzas K. 
Published: October 2006

Abstract
Aim: The aim of this report was to study the effect of high-fat (HF)/low-carbohydrate (CHO) diet on regulation of substrate metabolism in humans.
Methods: Ten healthy men consumed either a HF (75% energy as fat) or control (35%) diet for 6 d in random order. On d 7, blood glucose disappearance rate (Rd) was determined before and during a hyperinsulinemic euglycemic clamp. Substrate oxidation was determined by indirect calorimetry. Muscle biopsies were obtained prediet, postdiet, and postclamps.
Results: Rd was similar under basal conditions but slightly elevated (∼10%, P &lt; 0.05) during the last 30 min of the clamp after the HF diet. HF diet reduced CHO oxidation under basal (by ∼40%, P &lt; 0.05) and clamp conditions (by ∼20%, P &lt; 0.05), increased insulin-mediated whole-body nonoxidative glucose disposal (by 30%, P &lt; 0.05) and muscle glycogen storage (by ∼25%, P &lt; 0.05). Muscle pyruvate dehydrogenase complex activity was blunted under basal and clamp conditions after HF compared with control (P &lt; 0.05) and was accompanied by an approximately 2-fold increase (P &lt; 0.05) in pyruvate dehydrogenase kinase 4 (PDK4) mRNA and protein expression.
Conclusion: Short-term HF/low-CHO dietary intake did not induce whole-body insulin resistance, but caused a shift in im glucose metabolism from oxidation to glycogen storage. Insulin-stimulated CHO oxidation and muscle pyruvate dehydrogenase complex activity were blunted after the HF diet. Up-regulation of muscle PDK4 expression was an early molecular adaptation to these changes, and we showed for the first time in healthy humans, unlike insulin-resistant individuals, that insulin can suppress PDK4 but not PDK2 gene expression in skeletal muscle.
Differential Gene Expression Profile in Omental Adipose Tissue in Women with Polycystic Ovary Syndrome
Authors: Cortón Marta , Botella-Carretero José I. , Benguría Alberto , Villuendas Gemma , Zaballos Angel , San Millán José L. , Escobar-Morreale Héctor F. , Peral Belén 
Published: October 2006

Abstract
Context: The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of the syndrome.
Objective: The objective was to study the expression profiles of omental fat biopsy samples obtained from morbidly obese women with or without PCOS at the time of bariatric surgery.
Design: This was a case-control study.
Settings: We conducted the study in an academic hospital.
Patients: Eight PCOS patients and seven nonhyperandrogenic women submitted to bariatric surgery because of morbid obesity.
Interventions: Biopsy samples of omental fat were obtained during bariatric surgery.
Main Outcome Measure: The main outcome measure was high-density oligonucleotide arrays.
Results: After statistical analysis, we identified changes in the expression patterns of 63 genes between PCOS and control samples. Gene classification was assessed through data mining of Gene Ontology annotations and cluster analysis of dysregulated genes between both groups. These methods highlighted abnormal expression of genes encoding certain components of several biological pathways related to insulin signaling and Wnt signaling, oxidative stress, inflammation, immune function, and lipid metabolism, as well as other genes previously related to PCOS or to the metabolic syndrome.
Conclusion: The differences in the gene expression profiles in visceral adipose tissue of PCOS patients compared with nonhyperandrogenic women involve multiple genes related to several biological pathways, suggesting that the involvement of abdominal obesity in the pathogenesis of PCOS is more ample than previously thought and is not restricted to the induction of insulin resistance.
Synthesis of Copper Phthalocyanine-containing Hyperbranched Polymer Starting from 1,2-Bis(3,4-dicyanophenoxy)benzene and CuCl
Authors: Kwon Young , Hayakawa Teruaki , Kakimoto Masa-aki 
Published: October 2006

Abstract
A novel soluble hyperbranched polymer with copper phthalocyanine (CuPc) was successfully prepared by copper fusion technique of 1,2-bis(3,4-dicyanophenoxy)benzene and CuCl. The structure of copper phthalocyanine-containing hyperbranched polymer confirmed by IR, UV–vis absorption spectra. This polymer showed good solubility in DMF, DMAc, and high thermal stability.
New patterns in genetic and congenital otonephropathies
Authors: Bergstrom Lavonne , Thompson Patricia , Wood Raymond P. 
Published: October 2006

AbstractIn a series of chronic renal and congenitally deaf patients 24 were identified as having inborn renal and otologic disease. Sixteen patients, representing 14 families, had genetic disorders. Only two had the features of Alport's syndrome.The patients were classified as follows: 1) Probable Alport's — 2 patients (1 family); 2) Atypical hereditary nephritis and sensorineural hearing loss — 7 patients; 3) Renal and inner ear anomalies — 1 patient; 4) Renal, inner ear and multiple anomalies — 4 patients. The temporal bone pathology in one case showed primary neural atrophy and a mild Mondini malformation. In another a Scheibe defect and unusual calcific structures were found in the cochlear duct. 5) Renal, external or middle ear and multiple anomalies — 6 patients (5 families); 6) Renal, middle and inner ear anomalies and multiple anomalies — 2 patients. A temporal bone obtained from one case showed combined middle and inner ear defects. In the other, who had a chromosome defect, predominantly middle ear anomalies were found. 7) Nephrotic syndrome and congenital hearing loss — 1 patient; 8) Unclassified — 1 patient.Some cases represent entities apparently not previously described. Probably most interesting is the delineation of hereditary nephritis and deafness distinct from Alport's disease.
Bleomycin: Its utilization in the treatment of head and neck cancer
Authors: Bone Robert C. , Byfield John E. , Feren Alan P. , Seagren Stephen L. 
Published: October 2006

AbstractOriginally isolated as an antibiotic, bleomycin is a complex mixture of glycopeptides currently utilized against a variety of malignancies, among them epidermoid cancer of the head and neck. Because of unique independent pharmacological properties, bleomycin may be effectively used at several points in the natural history of tumors. Use of bleomycin as a single agent, as an adjunct to surgery and irradiation and as a palliative drug in head and neck cancer, is now advocated in scattered reports. The rationale for the utilization of bleomycin at the University of California, San Diego and San Diego Veterans Administration Hospitals is discussed. In addtion, examples from the authors' personal series of both response and adverse effects, suggestions for appropriate clinical monitoring to detect early toxicity, and tennets for management of side effects are included in the presentation.
Treatment of spastic dysphonia by recurrent laryngeal nerve section
Authors: Barton Richard Thomas 
Published: October 2006

AbstractThe problem of management of patients with spastic dysphonia has been complicated by a general resistance to speech therapy, psychotherapy, hypnotherapy, and drug therapy. Dedo introduced the concept of recurrent laryngeal nerve section in an attempt to eliminate the hyperfunction and excessive adduction of the vocal folds.Eleven patients were treated by RLN section with satisfactory results in 8 and some improvement in the other 3. The operation was found to be generally uncomplicated and required on average 4 days of hospitalization.Dedo's theory that spastic dysphonia is caused by a neurotropic viral‐induced proprioceptive nerve deficit represents a new search for organic cause. His most recent report of finding unmyelinated fibres in one‐third of the resected recurrent laryngeal nerves is of questionable significance. The evidence of deep emotional conflict and/or compulsive lifestyle is found in the majority of the patients, but the syndrome is not typical of an hysterical or conversion neurosis.Regardless of etiologic theory, RLN section is an effective treatment in selected, longstanding, and resistant instances of spastic dysphonia.
The effect of static tympanic pressure gradients on hearing sensitivity in normal subjects
Authors: Truswell William H. , Randolph Kenneth J. , Snyder G. Gordon 
Published: October 2006

AbstractThe effects of static tympanic air pressure gradients on hearing sensitivity was studied by introducing overpressures of 100 mm H2O to 400 mm H2O into the ear canals of 22 normal subjects. Sweep frequency threshold measures were obtained using a pressure‐tight probe transducer driven by a Bekesy automatic audiometer. These gradients of tympanic pressure disequilibrium produced threshold losses through 4000 Hz, most prominently for the region of 500 to 1000 Hz, that increased systematically with the degree of overpressure. The data may be useful in estimating the degree of conductive loss associated with middle ears presenting retraction without effusion and normally compliant though negatively skewed tympanograms.
The revised learning process questionnaire: A validation of a Western model of students' study approaches to the South Pacific context using confirmatory factor analysis
Authors: Phan Huy P. , Deo Bisun. 
Published: October 2006

Background. Research evidence seems to suggest that the social and cultural environments influence students' approaches to their study. This social and cultural contention has led to the rethinking and reconceptualization of theories (e.g. Biggs, 1987; Marton & Säljö, 1976) pertaining to student approaches to learning (SAL) in academic settings.Aims. The present research discusses two separate empirical studies on student learning approaches situated in the South Pacific region with two respective cohorts of secondary students. Study I involved the examination of secondary Pacific Islands students in their learning approaches using a modified version of Biggs' (1987) original Learning Process Questionnaire (LPQ). Study II involved the administration of a revised version of the LPQ (R‐LPQ‐2F; Kember, Biggs, & Leung, 2004) to another cohort of secondary Pacific Islands students.Sample. The first sample included 2,150 (1,285 girls, 865 boys) students and the second sample included 2,295 (1,363 girls, 932 boys) students.Methods. The factor structures of approaches to learning were examined by means of confirmatory factor analysis (CFA) using the LISREL program. Different a priori models were hypothesized and tested.Results. Results of Study I indicated a two‐factor structure solution to Biggs' LPQ, supporting Richardson's (1994) theoretical model of learning and emphasized the factors of Reproducing and Meaning. Study II indicated a hierarchical organization of two main study approaches – deep and surface – that are structured as higher‐order factors and a defined by four first‐order factors.Conclusion. The results from the two studies accentuate the important argument for the rethinking and reconceptualization of learning approaches, as well as for the redevelopment and modification of learning inventories such as the LPQ. They also suggest the importance of situating the theoretical paradigm of learning approaches in a social and cultural environment.
DNA Polymerase-β Is Expressed Early in Neurons of Alzheimer's Disease Brain and Is Loaded into DNA Replication Forks in Neurons Challenged with β-Amyloid
Authors: Copani Agata , Hoozemans Jeroen J. M. , Caraci Filippo , Calafiore Marco , Van Haastert Elise S. , Veerhuis Robert , Rozemuller Annemieke J. M. , Aronica Eleonora , Sortino Maria Angela , Nicoletti Ferdinando 
Published: October 2006

Cultured neurons exposed to synthetic β-amyloid (Aβ) fragments reenter the cell cycle and initiate a pathway of DNA replication that involves the repair enzyme DNA polymerase-β (DNA pol-β) before undergoing apoptotic death. In this study, by performing coimmunoprecipitation experiments on cross-linked nucleoprotein fragments from Aβ-treated neurons, we demonstrate that DNA pol-β coimmunoprecipitates with cell division cycle 45 (Cdc45) and with DNA primase in short nucleoprotein fragments. This indicates that DNA pol-β is loaded into neuronal DNA replication forks after Aβ treatment. In response to Aβ the canonical DNA-synthesizing enzyme DNA pol-δ also was loaded into neuronal replication forks, but at later times than DNA pol-β. Methoxyamine, an inhibitor of the apurinic/apyrimidinic endonuclease that allows for the recruitment of DNA pol-β during the process of base excision repair (BER), failed to affect coimmunoprecipitation between DNA pol-β and Cdc45, indicating that DNA pol-β loading to the replication forks is independent of DNA breaks. However, methoxyamine reduced DNA replication and ensuing apoptosis in neurons exposed to Aβ, suggesting that an efficient BER process allows DNA replication to proceed up to the threshold for death.These data demonstrate that DNA pol-β is an essential component of the DNA replication machinery in Aβ-treated neurons and additionally support the hypothesis of a close association of cell cycle events with neuronal death in Alzheimer's disease (AD). Accordingly, by investigating the neuronal expression of DNA pol-β, along with phosphorylated retinoblastoma protein and neurofibrillary changes in AD brain, we show an early involvement of DNA pol-β in the pathogenesis of AD.
Specificity of M and L Cone Inputs to Receptive Fields in the Parvocellular Pathway: Random Wiring with Functional Bias
Authors: Buzás Péter , Blessing Esther M. , Szmajda Brett A. , Martin Paul R. 
Published: October 2006

Many of the parvocellular pathway (PC) cells in primates show red–green spectral selectivity (cone opponency), but PC ganglion cells in the retina show no anatomical signs of cone selectivity. Here we asked whether responses of PC cells are compatible with “random wiring” of cone inputs. We measured long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cone inputs to PC receptive fields in the dorsal lateral geniculate of marmosets, using discrete stimuli (apertures and annuli) to achieve functional segregation of center and surround. Receptive fields between the fovea and 30° eccentricity were measured.We show that, in opponent PC cells, the center is dominated by one (L or M) cone type, with normally <20% contribution from the other cone type (high “cone purity”), whereas non-opponent cells have mixed L and M cone inputs to the receptive field center. Furthermore, opponent response strength depends on the overall segregation of L and M cone inputs to center and surround rather than exclusive input from one cone type to either region. These data are consistent with random wiring. The majority of PC cells in both foveal (<8°) and peripheral retina nevertheless show opponent responses. This arises because cone purity in the receptive field surround is at least as high as in the center, and the surround in nearly all opponent PC cells is dominated by the opposite cone type to that which dominates the center. These functional biases increase the proportion of opponent PC cells, but their anatomical basis is unclear.