bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses
Authors: Collins L Vincent , Hajizadeh Shahin , Holme Elisabeth , Jonsson Ing-Marie , Tarkowski Andrej 
Published: March 2004

AbstractWe report that mitochondrial DNA (mtDNA) is inflammatogenic in vitro and in vivo as a result of the presence of unmethylated CpG sequences and its oxidative status. Purified human and murine mtDNAs induced arthritis when injected intra-articularly (i.a.) in mice. Importantly, oligodeoxynucleotide that contained a single oxidatively damaged base also induced arthritis when injected i.a. in mice. In contrast, neither human nor murine nuclear DNA induced inflammation. mtDNA-induced arthritis was neither B cell- nor T cell-dependent but was mediated by monocytes/macrophages. mtDNA-induced nuclear factor-κB stimulation resulted in the production of tumor necrosis factor α, a potent, arthritogenic factor. Finally, extracellular mtDNA was detected in the synovial fluids of rheumatoid arthritis patients but not of control subjects. We conclude that endogenous mtDNA displays inflammatogenic properties as a result of its content of unmethylated CpG motifs and oxidatively damaged adducts.
Effects ofcis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes
Authors: Leiro José , Álvarez Ezequiel , Arranz Juan A , Laguna Reyes , Uriarte Eugenio , Orallo Francisco 
Published: March 2004

AbstractThis study investigated for the first time the effects of the cis isomer of resveratrol (c-RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)-2 and inducible cyclooxygenase (COX)-2. Treatment with 1–100 μM c-RESV significantly inhibited intracellular and extracellular ROS production, and c-RESV at 10–100 μM significantly reduced RNS production. c-RESV at 1–100 μM was ineffective for scavenging superoxide radicals (O2•−), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c-RESV at 10–100 μM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c-RESV at 100 μM decreased NOS-2 and COX-2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN-γ)-treated macrophages. At 10–100 μM, c-RESV also significantly inhibited NOS-2 and COX-2 protein synthesis and decreased prostaglandin E2 (PGE2) production. These results indicate that c-RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O2•− and of the proinflammatory mediators NO• and PGE2).
Efficacy of leukocyte depletion of residual pump blood
Authors: Heerdt E M , Fransen E J , Maessen J G , de Jong D S 
Published: March 2004

In this study, we examined whether leukocyte depletion from the residual heart-lung machine blood at the end of cardiopulmonary bypass (CPB) has an effect on the leukocyte counts in the systemic circulation. Twenty-six patients undergoing coronary artery bypass grafting (CABG) were randomly allocated to a leukocyte-depletion group or a control group. In the leukocyte-depletion group ( n = 13), all residual blood (400 mL to 1.4 L) was filtered by leukocyte-removal filters (Pall RS01) and reinfused to the patient after CPB, whereas, in the control group, an identical amount of residual blood after bypass was reinfused without filtration ( n = 13). Leukocyte-depleted allogeneic blood was transfused if needed. Preoperative risk profiles, pump support and duration of aortic crossclamping time were identical in both patient groups (ns). Leukocyte depletion removed more than 96% of leukocytes from the residual retransfused blood ( p < 0.01) and significantly reduced circulating leukocytes ( p < 0.05) compared with the control group. Remarkably, lower numbers of circulating leukocytes were found, not at 1 hour after reinfusion, but at 4 and 8 hours after reinfusion ( p < 0.05). There were no statistical differences between the two groups with respect to postoperative blood loss, the number of transfused packed red cells and mechanical ventilation time. These results show that leukocytes can be removed from the residual blood of the heart-lung machine after CPB very effectively. Furthermore, this leukocyte depletion results in a long-term effect, the clinical significance of which has to be elucidated in ongoing studies.
ABO-incompatible heart transplantation: a perfusion strategy
Authors: Foreman C , Gruenwald C , West L 
Published: March 2004

Infants with fatal cardiac disease often die awaiting transplantation because of the shortage of donor hearts. The Hospital for Sick Children (HSC), Toronto, Canada, has researched and applied the concept of crossing the blood group compatibility barrier. Heart transplantation at HSC unrestricted by ABO compatibility greatly contributed to decreasing the mortality rate among infants on the waiting list from 58% to 10%. From January 1996 to January 2002, 16 infants less than 14 months of age received ABO-incompatible heart transplants at our institution. The cardiopulmonary bypass (CPB) circuit is primed with additional volume to replace the patient’s blood volume. Packed red blood cells (PRBC) used in priming must be ABO-compatible with the recipient. All plasma components and platelets must contain no anti-A or anti-B antibodies to donor or recipient. CPB is initiated and the patient’s venous blood is collected into a transfusion bag and sent to the blood bank. The total amount collected should be one and a half to two times the patient’s blood volume. The plasma is separated and discarded, returning only the PRBC, thus reducing the concentration of circulating antibodies to blood group antigens. Our team has experienced an 87% survival rate with this technique. The success is believed to be associated with the recipients’ immunologic immaturity. Newborns do not produce isohemagglutinins, and serum anti-A and anti-B antibody titers usually remain low until 12-14 months of age. The complement system is not fully developed, therefore, the mediators of hyperacute rejection are absent during early infancy. Heart transplantation unrestricted by the need for ABO compatibility would effectively expand the available donor pool and decrease waiting times.
Test rig and software for recording force and muscle activity
Authors: Outten Alan G , Cullen Gerard , Stokes Maria J 
Published: March 2004

Objective: To design a test rig for measuring isometric quadriceps' force which is easily adjustable, dismountable, transportable, relatively lightweight and inexpensive. Also to produce a data-acquisition software program that enables real-time feedback of the force signal, automatic analysis of maximal voluntary contraction (MVC) force, and submaximal target levels to be displayed on a computer screen, as well as acquisition of other signals such as electromyographic (EMG) activity. Methodology: A test rig was constructed using an aluminium tubing system which was fully adjustable and could be flat-packed for transportation. The data acquisition software program was written in Borland C++ and is suitable for use with an IBM-compatible PC. The interface is user friendly, and the entire testing system is relatively inexpensive compared to commercially available systems. Conclusions: The equipment is suitable for various applications in rehabilitation research and clinical testing, and is suitable for examining different muscles. Further technical details are freely available from the authors.
Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial
Authors: Hesse Stefan , Reiter Frank , Konrad Matthias , Jahnke Matthias T 
Published: March 2004

Objective: To investigate whether the combined approach of botulinum toxin type A (BtxA) and electrical stimulation was more effective than the toxin alone in the treatment of chronic upper limb spasticity after stroke. Design: Randomized, placebo-controlled study with four treatment groups: 1000 units BtxA (Dysport®) + electrical stimulation (A), 1000 units BtxA (B), placebo + electrical stimulation (C) and placebo (D). Setting: A neurological rehabilitation clinic. Subjects: Twenty-four stroke patients with chronic upper limb spasticity after stroke, six patients in each treatment group. Interventions: Intramuscular injection of either toxin or placebo into six upper limb flexor muscles. In group A and C additional electrical stimulation of the injected muscles with surface electrodes, three times half an hour each day for three days. Main outcome measures: Muscle tone rated with the modified Ashworth score, limb position at rest and difficulties encountered during three upper limb motor tasks assessed before and 2, 6 and 12 weeks after injection. Results: Most improvements were observed in patients of group A. Cleaning the palm ( p = 0.004) differed across groups. Pairwise comparison for this target variable showed that group A differed from group B and D ( p <0.01), but not from C. Indicative across-group differences were obtained for elbow spasticity reduction ( p = 0.011), and improvement of putting the arm through a sleeve ( p = 0.020). Conclusions: The placebo-controlled trial favours the conceptthat electrical stimulation enhances the effectiveness of BtxA in the treatment of chronic upper limb flexor spasticity after stroke.
Alternatives for measuring knee extension strength of the elderly at home
Authors: Bohannon Richard W 
Published: March 2004

Objective: To examine the construct validity of three measures of knee extension strength obtained from elderly individuals. Design: Retrospective and cross-sectional. Setting: Home care. Subjects: Forty-one consecutively treated patients (mean age 79.2 years). Measures: Knee extension strength was measured using manual muscle testing, hand-held dynamometry, and the sit-to-stand test. Results: Convergent construct validity was supported by the significant correlations between the measures ( r s = 0.578–0.702). Discriminant construct validity was confirmed by the finding of significant differences in the manual muscle test scores and in the hand-held dynamometer measures of patients who were unable versus able to stand from a chair without the upper extremities or help. The sensitivity of the two measures for discriminating between patients able versus unable to stand from a chair was 90.9% for manual testing and 68.2% for dynamometry. The specificity was 78.9% for manual testing and 94.7% for dynamometry. Conclusion: The results of this study show that the three measures employed to characterize knee extension strength are valid when employed with elderly patients in a home care setting.
Functional motor abilities of children with cerebral palsy: a systematic literature review of assessment measures
Authors: Ketelaar Marjolijn , Vermeer Adri , Helders Paul Jm 
Published: March 2004

Objective: To provide an overview of functional assessment measures for children with cerebral palsy, supporting the selection of measures and the interpretation of results from measures. Methods: Instruments were selected on the basis of a literature search of the Medline, Sportdisk and PsychLIT databases. Issues reviewed: Instruments were reviewed with respect to target group, purpose, nature, type and psychometric properties. Results: In the literature 17 instruments that are used in paediatric rehabilitation and paediatric physical therapy to assess the functional motor abilities of children with cerebral palsy were found. While there is an urgent need for measures that can evaluate change in functional abilities, it was found that most measures are developed and validated for discriminative purposes. Conclusions: Although instruments developed within the lastdecade meet psychometric criteria more adequately than those developed previously, it is concluded that only two evaluative assessment measures, the Gross Motor Function Measure (GMFM) and the Pediatric Evaluation of Disability Inventory (PEDI), fulfil the criteria of reliability and validity with respect to responsiveness to change.
Evaluation of a nurse-led multidisciplinary neurological rehabilitation programme using the Nottingham Health Profile
Authors: Sitzia J , Haddrell V , Rice-Oxley M 
Published: March 2004

Objective: To ascertain whether or not an inpatient multidisciplinary treatment programme for patients with Parkinson's disease or multiple sclerosis resulted in a measurable change in patients' health-related quality of life (HRQL). Design: Assessments of HRQL were made one week before admission and approximately one month post discharge. Setting: Six-bed Neurological Rehabilitation Unit at Worthing Hospital on the south coast of England. Subjects: Fifty-eight patients with Parkinson's disease and 33 patients with multiple sclerosis. Interventions: All patients received an individually adapted, multidisciplinary rehabilitation programme. The programmes lasted from 5 to 10 days. Main outcome measures: HRQL scores on the Nottingham Health Profile Part 1 (NHP-1). Results: Overall post-treatment NHP-1 scores were significantly better than overall pretreatment scores for both the Parkinson's group ( z = 2.6, p <0.01) and the multiple sclerosis group ( z = 2.1, p <0.05). Sixty-four per cent of patients perceived an overall improvement. The strongest improvement was in ‘physical mobility’ in the multiple sclerosis group ( z = 3.0, p <0.01) and in ‘emotional reactions' in the Parkinson's group ( z = 2.9, p <0.01). Conclusions: These results suggest that the multidisciplinary inpatient approach in neurological rehabilitation has identifiable short-term benefits for the majority of patients. A randomized trial with longer follow-up is required to confirm this.
Phase II Trial of Cetuximab in Patients With Refractory Colorectal Cancer That Expresses the Epidermal Growth Factor Receptor
Authors: Saltz Leonard B. , Meropol Neal J. , Loehrer Patrick J. , Needle Michael N. , Kopit Justin , Mayer Robert J. 
Published: March 2004

Purpose To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Patients and Methods Phase II, open-label clinical trial. Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation. Patients were required to have received irinotecan, either alone or in a combination regimen, and to have demonstrated clinical failure on this regimen before study entry. Cetuximab was administered weekly by intravenous infusion. The first dose of 400 mg/m2 was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m2 during the course of 1 hour. Results Fifty-seven eligible patients were treated. All were assessable for toxicity and response. The most commonly encountered grade 3 to 4 adverse events, regardless of relationship to study drug, were an acne-like skin rash, predominantly on the face and upper torso (86% with any grade; 18% with grade 3), and a composite of asthenia, fatigue, malaise, or lethargy (56% with any grade, 9% with grade 3). Two patients (3.5%) experienced grade 3 allergic reactions requiring discontinuation of study treatment. A third patient experienced a grade 3 allergic reaction that resolved, and the patient continued on the study. Neither diarrhea nor neutropenia were dose limiting in any of the 57 patients treated. Five patients (9%; 95% CI, 3% to 19%) achieved a partial response. Twenty-one additional patients had stable disease or minor responses. The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer is 6.4 months. Conclusion Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease.
GATA-4 and GATA-6 Modulate Tissue-Specific Transcription of the Human Gene for P450c17 by Direct Interaction with Sp1
Authors: Flück Christa E. , Miller Walter L. 
Published: March 2004

AbstractCytochrome P450c17 catalyzes steroidogenic 17α-hydroxylase and 17,20 lyase activities. Expression of the gene for P450c17 is cAMP dependent, tissue specific, developmentally programmed, and varies among species. Binding of Sp1, Sp3, and NF1-C (nuclear factor 1-C) to the first 227 bp of 5′flanking DNA (−227/LUC) is crucial for basal transcription in human NCI-H295A adrenal cells. Human placental JEG-3 cells contain Sp1, Sp3, and NF1, but do not express −227/LUC, even when transfected with a vector expressing steroidogenic factor 1 (SF-1). Therefore, other factors are essential for basal expression of P450c17. Deoxyribonuclease I footprinting and EMSAs identified a GATA consensus site at −64/−58 and an SF-1 site at −58/−50. RT-PCR identified GATA-4, GATA-6, and SF-1 in NCI-H295A cells and GATA-2 and GATA-3, but not GATA-4, GATA-6, or SF-1 in JEG-3 cells. Cotransfection of either GATA-4 or GATA-6 without SF-1 activated −227/LUC in JEG-3 cells, but cotransfection of GATA-2 or GATA-3 with or without SF-1 did not. Surprisingly, mutation of the GATA binding site in −227/LUC increased GATA-4 or GATA-6 induced activity, whereas mutation of the Sp1/Sp3 site decreased it. Furthermore, promoter constructs including the GATA site, but excluding the Sp1/Sp3 site at −196/−188, were not activated by GATA-4 or GATA-6, suggesting an interaction between Sp1/Sp3 and GATA-4 or GATA-6. Glutathione-S-transferase pull-down experiments and coimmunoprecipitation demonstrated interaction between GATA-4 or GATA-6 and Sp1, but not Sp3. Chromatin immunoprecipitation assays confirmed that this GATA-4/6 interaction with Sp1 occurred at the Sp site in the P450c17 promoter in NCI-H295A cells. Demethylation with 5-aza-2-deoxycytidine permitted JEG-3 cells to express endogenous P450c17, SF-1, GATA-4, GATA-6, and transfected −227/LUC. Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells.
Generation of Thyrotropin-Releasing Hormone Receptor 1-Deficient Mice as an Animal Model of Central Hypothyroidism
Authors: Rabeler Roland , Mittag Jens , Geffers Lars , Rüther Ulrich , Leitges Michael , Parlow Albert F. , Visser Theo J. , Bauer Karl 
Published: March 2004

AbstractTo provide an animal model of central hypothyroidism, mice deficient in the TRH-receptor 1 (TRH-R1) gene were generated by homologous recombination. The pituitaries of TRH-R1−/− mice are devoid of any TRH-binding capacity, demonstrating that TRH-R1 is the only receptor localized on TRH target cells of the pituitary. With the exception of some retardation in growth rate, TRH-R1−/− mice appear normal, but compared with control animals they exhibit a considerable decrease in serum T3, T4, and prolactin (PRL) levels but not in serum TSH levels. In situ hybridization histochemistry and real-time RT-PCR analysis revealed that in adult TRH-R1−/− animals TSHβ-mRNA expression is not impaired whereas PRL mRNA and GH mRNA levels are considerably reduced compared with control mice. The numbers of thyrotropes, somatotropes, and lactotropes, however, are not affected by the deletion of the TRH-R1 gene. The mutant mice are fertile, and the dams nourish their pups well, indicating that TRH is not a decisive factor for suckling-induced PRL release. In situ hybridization and quantitative RT-PCR analysis, furthermore, revealed that, as in control animals, pituitary PRL-mRNA expression in TRH-R1−/− is considerably increased during lactation, albeit strongly reduced as compared with lactating control animals.
Blocking actions of glibenclamide on ATP-sensitive K+ channels in pig urethral myocytes
Authors: Teramoto Noriyoshi , Zhu Hai-Lei , Ito Yushi 
Published: March 2004

Abstract
The inhibitory effects of glibenclamide on the levcromakalim-induced ATP-sensitive K+ (KATP) channels were investigated with cell-attached configuration in pig proximal urethra. Application of 10 μm glibenclamide reversibly inhibited the activity of the 100 μm levcromakalim-induced KATP channel, decreasing not only the channel open probability but also the amplitude of unitary current. The inhibitory concentration-response curve of the glibenclamide-induced sublevel conductance of KATP channel was shifted to the right (IC50=4.7 μm), compared with the levcromakalim-induced KATP channel (full conductance, IC50=0.5 μm). Glibenclamide is the first reported sulphonylurea to selectively block KATP channel, not only by decreasing the channel activity but also by reducing the unitary amplitude in smooth muscle.
Inhibition of acetylcholinesterase by Tea Tree oil
Authors: Mills Clive , Cleary Brian V , Walsh John J , Gilmer John F 
Published: March 2004

Abstract
Pediculosis is a widespread condition reported in schoolchildren. Treatment most commonly involves the physical removal of nits using fine-toothcombs and the chemical treatment of adult lice and eggs with topical preparations. The active constituents of these preparations frequently exert their effects through inhibition of acetylcholinesterase (AChE, EC 3.1.1.7). Increasing resistance to many preparations has led to the search for more effective treatments. Tea Tree oil, otherwise known as Melaleuca oil, has been added to several preparations as an alternative treatment of head lice infestations. In this study two major constituents of Tea Tree oil, 1,8-cineole and terpinen-4-ol, were shown to inhibit acetylcholinesterase at IC50 values (inhibitor concentrations required to give 50% inhibition) of 0.04 and 10.30 mm, respectively. Four samples of Tea Tree oil tested (Tisserand, Body Treats, Main Camp and Irish Health Culture Association Pure Undiluted) showed anticholinesterase activity at IC50 values of 0.05, 0.10, 0.08 and 0.11 μL mL−1, respectively. The results supported the hypothesis that the insecticidal activity of Tea Tree oil was attributable, in part, to the anticholinesterase activity of Tea Tree oil.