bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ECOS-16 questionnaire for the evaluation of health related quality of life in post-menopausal women with osteoporosis
Authors: Badia Xavier , Díez-Pérez Adolfo , Lahoz Raquel , Lizán Luis , Nogués Xavier , Iborra Jordi 
Published: August 2004

Abstract
Background
The aim of this study is to validate the questionnaire ECOS-16 (Assessment of health related quality of life in osteoporosis) for the evaluation of health related quality of life (HRQoL) in post-menopausal women with osteoporosis.

Methods
An observational, prospective and multi-centre study was carried out among post-menopausal women with osteoporosis in primary care centres and hospital outpatient clinics. All patients attended 2 visits: at baseline and at 6 months. In addition, the subgroup of outpatients attended another visit a month after the baseline to assess the test-retest reliability. The psychometric properties of the questionnaire were evaluated in terms of feasibility, validity (content validity and construct validity) and internal consistency in baseline, and in terms of test-retest reliability and responsiveness to change in visit at month and visit at 6 months, respectively. In all visits, ECOS-16, EUROQoL-5D (EQ-5D) and four 7-point items about health status (general health status, back pain, limitation in daily activities and emotional status) were administered, whereas only outpatients were given MINI-OQLQ (Mini Osteoporosis Quality of Life Questionnaire), besides all clinical variables; and sociodemographic variables at baseline.

Results
316 women were consecutively included, 212 from primary care centres and 104 from hospital outpatient clinics. Feasibility: 94.3% of patients answered all items of the questionnaire. The mean administration time was 12.3 minutes. Validity: factor analysis suggested that the questionnaire was unidimensional. In the multivariate analysis, patients with vertebral fractures, co-morbidity and a lower education level showed to have worse HRQoL. Moderate to high correlations were found between the ECOS-16 score and the other health status questionnaires (0.47–0.82). Reliability: internal consistency (Cronbach's α) was 0.92 and test-retest reliability (ICC) was 0.80. Responsiveness to change: ECOS-16 scores increased according to change perceived by the patient, as well as the effect size (ranges between 1.35 to 0.43), the greater the perception of change in patients' general health status, the greater the changes in patients' scores. The Minimal Clinically Important Difference (MCID) suggested a change of 0.5 points in the ECOS-16 score, representing the least improvement in general health status due to their osteoporosis: "slightly better".

Conclusion
ECOS-16 has been proven preliminarily to have good psychometric properties, so that it can be potentially a useful tool to evaluate HRQoL of post-menopausal women with osteoporosis in research and routine clinical practice.
The AMC Linear Disability Score project in a population requiring residential care: psychometric properties
Authors: Holman Rebecca , Lindeboom Robert , Vermeulen Marinus , de Haan Rob J 
Published: August 2004

Abstract
Background
Currently there is a lot of interest in the flexible framework offered by item banks for measuring patient relevant outcomes, including functional status. However, there are few item banks, which have been developed to quantify functional status, as expressed by the ability to perform activities of daily life.

Method
This paper examines the psychometric properties of the AMC Linear Disability Score (ALDS) project item bank using an item response theory model and full information factor analysis. Data were collected from 555 respondents on a total of 160 items.

Results
Following the analysis, 79 items remained in the item bank. The remaining 81 items were excluded because of: difficulties in presentation (1 item); low levels of variation in response pattern (28 items); significant differences in measurement characteristics for males and females or for respondents under or over 85 years old (26 items); or lack of model fit to the data at item level (26 items).

Conclusions
It is conceivable that the item bank will have different measurement characteristics for other patient or demographic populations. However, these results indicate that the ALDS item bank has sound psychometric properties for respondents in residential care settings and could form a stable base for measuring functional status in a range of situations, including the implementation of computerised adaptive testing of functional status.
Construction of a questionnaire measuring outpatients' opinion of quality of hospital consultation departments
Authors: Gasquet Isabelle , Villeminot Sylvie , Estaquio Carla , Durieux Pierre , Ravaud Philippe , Falissard Bruno 
Published: August 2004

Abstract
Background
Few questionnaires on outpatients' satisfaction with hospital exist. All have been constructed without giving enough room for the patient's point of view in the validation procedure. The main objective was to develop, according to psychometric standards, a self-administered generic outpatient questionnaire exploring opinion on quality of hospital care.

Method
First, a qualitative phase was conducted to generate items and identify domains using critical analysis incident technique and literature review. A list of easily comprehensible non-redundant items was defined using Delphi technique and a pilot study on outpatients. This phase involved outpatients, patient association representatives and experts. The second step was a quantitative validation phase comprised a multicenter study in 3 hospitals, 10 departments and 1007 outpatients. It was designed to select items, identify dimensions, measure reliability, internal and concurrent validity. Patients were randomized according to the place of questionnaire completion (hospital v. home) (participation rate = 65%). Third, a mail-back study on 2 departments and 248 outpatients was conducted to replicate the validation (participation rate = 57%).

Results
A 27-item questionnaire comprising 4 subscales (appointment making, reception facilities, waiting time and consultation with the doctor). The factorial structure was satisfactory (loading >0.50 on each subscale for all items, except one item). Interscale correlations ranged from 0.42 to 0.59, Cronbach α coefficients ranged from 0.79 to 0.94. All Item-scale correlations were higher than 0.40. Test-retest intraclass coefficients ranged from 0.69 to 0.85. A unidimensional 9-item version was produced by selection of one third of the items within each subscale with the strongest loading on the principal component and the best item-scale correlation corrected for overlap. Factors related to satisfaction level independent from departments were age, previous consultations in the department and satisfaction with life. Completion at hospital immediately after consultation led to an overestimation of satisfaction. No satisfaction score differences existed between spontaneous respondents and patients responding after reminder(s).

Conclusion
Good estimation of patient opinion on hospital consultation performance was obtained with these questionnaires. When comparing performances between departments or the same department over time scores need to be adjusted on 3 variables that influence satisfaction independently from department. Completion of the questionnaire at home is preferable to completion in the consultation facility and reminders are not necessary to produce non-biased data.
A dual function fusion protein of Herpes simplex virus type 1 thymidine kinase and firefly luciferase for noninvasive in vivoimaging of gene therapy in malignant glioma
Authors: Söling Ariane , Theiß Christian , Jungmichel Stephanie , Rainov Nikolai G 
Published: August 2004

Abstract
Background
Suicide gene therapy employing the prodrug activating system Herpes simplex virus type 1 thymidine kinase (HSV-TK)/ ganciclovir (GCV) has proven to be effective in killing experimental brain tumors. In contrast, glioma patients treated with HSV-TK/ GCV did not show significant treatment benefit, most likely due to insufficient transgene delivery to tumor cells. Therefore, this study aimed at developing a strategy for real-time noninvasive in vivo monitoring of the activity of a therapeutic gene in brain tumor cells.

Methods
The HSV-TK gene was fused to the firefly luciferase (Luc) gene and the fusion construct HSV-TK-Luc was expressed in U87MG human malignant glioma cells. Nude mice with subcutaneous gliomas stably expressing HSV-TK-Luc were subjected to GCV treatment and tumor response to therapy was monitored in vivo by serial bioluminescence imaging. Bioluminescent signals over time were compared with tumor volumes determined by caliper.

Results
Transient and stable expression of the HSV-TK-Luc fusion protein in U87MG glioma cells demonstrated close correlation of both enzyme activities. Serial optical imaging of tumor bearing mice detected in all cases GCV induced death of tumor cells expressing the fusion protein and proved that bioluminescence can be reliably used for repetitive and noninvasive quantification of HSV-TK/ GCV mediated cell kill in vivo.

Conclusion
This approach may represent a valuable tool for the in vivo evaluation of gene therapy strategies for treatment of malignant disease.
Regulation of Bone Mass and Bone Turnover by Neuronal Nitric Oxide Synthase
Authors: van’t Hof Robert J. , MacPhee Jeny , Libouban Helene , Helfrich Miep H. , Ralston Stuart H. 
Published: August 2004

Abstract
Nitric oxide (NO) is produced by NO synthase (NOS) and plays an important role in the regulation of bone cell function. The endothelial NOS isoform is essential for normal osteoblast function, whereas the inducible NOS isoform acts as a mediator of cytokine effects in bone. The role of the neuronal isoform of NOS (nNOS) in bone has been studied little thus far. Therefore, we investigated the role of nNOS in bone metabolism by studying mice with targeted inactivation of the nNOS gene. Bone mineral density (BMD) was significantly higher in nNOS knockout (KO) mice compared with wild-type controls, particularly the trabecular BMD (P &lt; 0.01). The difference in BMD between nNOS KO and control mice was confirmed by histomorphometric analysis, which showed a 67% increase in trabecular bone volume in nNOS KO mice when compared with controls (P &lt; 0.001). This was accompanied by reduced bone remodeling, with a significant reduction in osteoblast numbers and bone formation surfaces and a reduction in osteoclast numbers and bone resorption surfaces. Osteoblasts from nNOS KO mice, however, showed increased levels of alkaline phosphatase and no defects in proliferation or bone nodule formation in vitro, whereas osteoclastogenesis was increased in nNOS KO bone marrow cultures. These studies indicate that nNOS plays a hitherto unrecognized but important physiological role as a stimulator of bone turnover. The low level of nNOS expression in bone and the in vitro behavior of nNOS KO bone cells indicate that these actions are indirect and possibly mediated by a neurogenic relay.
Development and Application of a Rat Ovarian Gene Expression Database
Authors: Jo Misung , Gieske Mary C. , Payne Charles E. , Wheeler-Price Sarah E. , Gieske Joseph B. , Ignatius Ignatius V. , Curry Thomas E. , Ko CheMyong 
Published: August 2004

AbstractThe pituitary gonadotropins play a key role in follicular development and ovulation through the induction of specific genes. To identify these genes, we have constructed a genome-wide rat ovarian gene expression database (rOGED). The database was constructed from total RNA isolated from intact ovaries, granulosa cells, or residual ovarian tissues collected from immature pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin-treated rats at 0 h (no PMSG), 12 h, and 48 h post PMSG, as well as 6 and 12 h post human chorionic gonadotropin. The total RNA was used for DNA microarray analysis using Affymetrix Rat Expression Arrays 230A and 230B (Affymetrix, Santa Clara, CA). The microarray data were compiled and used for display of individual gene expression profiles through specially developed software. The final rOGED provides immediate analysis of temporal gene expression profiles for over 28,000 genes in intact ovaries, granulosa cells, and residual ovarian tissue during follicular growth and the preovulatory period. The accuracy of the rOGED was validated against the gene profiles for over 20 known genes. The utility of the rOGED was demonstrated by identifying six genes that have not been described in the rat periovulatory ovary. The mRNA expression patterns and cellular localization for each of these six genes (estrogen sulfotransferase, synaptosomal-associated protein 25 kDa, runt-related transcription factor, calgranulin B, α1-macroglobulin, and MAPK phosphotase-3) were confirmed by Northern blot analyses and in situ hybridization, respectively. The current findings demonstrate that the rOGED can be used as an instant reference for ovarian gene expression profiles, as well as a reliable resource for identifying important yet, to date, unknown ovarian genes.
Mechanisms of Hemorrhage-Induced Hepatic Insulin Resistance: Role of Tumor Necrosis Factor-α
Authors: Ma Yuchen , Toth Balazs , Keeton Adam B. , Holland LaWanda T. , Chaudry Irshad H. , Messina Joseph L. 
Published: August 2004

AbstractHemorrhage, sepsis, burn injury, surgical trauma and critical illness all induce insulin resistance. Recently we found that trauma and hemorrhage acutely induced hepatic insulin resistance in the rat. However, the mechanisms of this hemorrhage-induced acute hepatic insulin resistance are unknown. Here we report on the mechanisms of this hepatic insulin resistance. Protein levels and phosphorylation of the insulin receptor and insulin receptor substrate-1/2 (IRS-1/2) were measured, as was the association between IRS-1/2 and phosphatidylinositol 3-kinase (PI3K). Also examined were the hepatic expression of TNFα and TNFα-induced serine phosphorylation of IRS-1. Insulin receptor and IRS-1/2 protein levels and insulin-induced tyrosine phosphorylation of the insulin receptor were unaltered. In contrast, insulin-induced tyrosine phosphorylation of IRS-1/2 and association between IRS-1/2 and PI3K were dramatically reduced after hemorrhage. Hepatic levels of TNFα mRNA and protein were increased as was phosphorylation of IRS-1 serine 307 after hemorrhage. Our data provide the first evidence that compromised IRS-1/2 tyrosine phosphorylation and their association with PI3K contribute to hemorrhage-induced acute hepatic insulin resistance. Increased local TNFα may play a role in inducing this hepatic insulin resistance after trauma and hemorrhage.
Triiodothyronine Stimulates Food Intake via the Hypothalamic Ventromedial Nucleus Independent of Changes in Energy Expenditure
Authors: Kong Wing May , Martin Niamh M. , Smith Kirsty L. , Gardiner James V. , Connoley Ian P. , Stephens David A. , Dhillo Waljit S. , Ghatei Mohammad A. , Small Caroline J. , Bloom Stephen R. 
Published: August 2004

AbstractIncreased food intake is characteristic of hyperthyroidism, although this is presumed to compensate for a state of negative energy balance. However, here we show that the thyroid hormone T3 directly stimulates feeding at the level of the hypothalamus. Peripheral administration of T3 doubled food intake in ad libitum-fed rats over 2 h and induced expression of the immediate early gene, early growth response-1, in the hypothalamic ventromedial nucleus (VMN), whereas maintaining plasma-free T3 levels within the normal range. T3-induced feeding occurred without altering energy expenditure or locomotion. Injection of T3 directly into the VMN produced a 4-fold increase in food intake in the first hour. The majority of T3 in the brain is reported to be produced by tissue-specific conversion of T4 to T3 by the enzyme type 2 iodothyronine deiodinase (D2). Hypothalamic D2 mRNA expression showed a diurnal variation, with a peak in the nocturnal feeding phase. Hypothalamic D2 mRNA levels also increased after a 12- and 24-h fast, suggesting that local production of T3 may play a role in this T3 feeding circuit. Thus, we propose a novel hypothalamic feeding circuit in which T3, from the peripheral circulation or produced by local conversion, stimulates food intake via the VMN.
Small-Molecule Insulin Mimetic Reduces Hyperglycemia and Obesity in a Nongenetic Mouse Model of Type 2 Diabetes
Authors: Strowski Mathias Z. , Li Zhihua , Szalkowski Deborah , Shen Xiaolan , Guan Xiao-Ming , Jüttner Stefan , Moller David E. , Zhang Bei B. 
Published: August 2004

Abstract
Adiposity positively correlates with insulin resistance and is a major risk factor of type 2 diabetes. Administration of exogenous insulin, which acts as an anabolic factor, facilitates adipogenesis. Recently nonpeptidal insulin receptor (IR) activators have been discovered. Here we evaluate the effects of the orally bioavailable small-molecule IR activator (Compound-2) on metabolic abnormalities associated with type 2 diabetes using a nongenetic mouse model in comparison with the effects of a novel non-thiazolidinedione (nTZD) peroxisome proliferator-activated receptor-γ agonist. Both Compound-2 and nTZD alleviated fasting and postprandial hyperglycemia; accelerated glucose clearance rate; and normalized plasma levels of nonesterified fatty acids, triglycerides, and leptin. Unlike nTZD, which increased body weight gain, and total fat mass, which is a common feature for PPARγ agonists, Compound-2 prevented body weight gain and hypertrophy of brown, and white adipose tissue depots and the development of hepatic steatosis in the mouse model of type 2 diabetes. The effect of the two compounds on proximal steps in insulin signal transduction pathway was analyzed in tissues. Compound-2 enhanced insulin-stimulated phosphorylation of IR tyrosine and/or Akt in the liver, skeletal muscle, and white adipose tissue, whereas nTZD potentiated the phosphorylation of IR and Akt in the adipose tissue only. In conclusion, small-molecule IR activators have unique features as insulin sensitizers and hold potential utility in the treatment of type 2 diabetes and obesity.
Dissecting Linear and Conformational Epitopes on the Native Thyrotropin Receptor
Authors: Ando Takao , Latif Rauf , Daniel Samira , Eguchi Katsumi , Davies Terry F. 
Published: August 2004

AbstractThe TSH receptor (TSHR) is the primary antigen in Graves’ disease. In this condition, autoantibodies to the TSHR that have intrinsic thyroid-stimulating activity develop. We studied the epitopes on the native TSHR using polyclonal antisera and monoclonal antibodies (mAbs) derived from an Armenian hamster model of Graves’ disease. Of 14 hamster mAbs analyzed, five were shown to bind to conformational epitopes including one mAb with potent thyroid-stimulating activity. Overlapping conformational epitopes were determined by cell-binding competition assays using fluorescently labeled mAbs. We identified two distinct conformational epitopes: epitope A for both stimulating and blocking mAbs and epitope B for only blocking mAbs. Examination of an additional three mouse-derived stimulating TSHR-mAbs also showed exclusive binding to epitope A. The remaining nine hamster-derived mAbs were neutral or low-affinity blocking antibodies that recognized linear epitopes within the TSHR cleaved region (residues 316–366) (epitope C). Serum from the immunized hamsters also recognized conformational epitopes A and B but, in addition, also contained high levels of TSHR-Abs interacting within the linear epitope C region. In summary, these studies indicated that the natively conformed TSHR had a restricted set of epitopes recognized by TSHR-mAbs and that the binding site for stimulating TSHR-Abs was highly conserved. However, high-affinity TSHR-blocking antibodies recognized two conformational epitopes, one of which was indistinguishable from the thyroid-stimulating epitope. Hence, TSHR-stimulating and blocking antibodies cannot be distinguished purely on the basis of their conformational epitope recognition.
Regulation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT1-Dependent Genes by RET/PTC (Rearranged in Transformation/Papillary Thyroid Carcinoma) Oncogenic Tyrosine Kinases
Authors: Hwang Eun Suk , Kim Dong Wook , Hwang Jung Hwan , Jung Hye Sook , Suh Jae Mi , Park Young Joo , Chung Hyo Kyun , Song Jung Hun , Park Ki Cheol , Park Su Hyeon , Yun Hwan-Jung , Kim Jin Man , Shong Minho 
Published: August 2004

AbstractChimeric RET/PTC (rearranged in transformation/papillary thyroid carcinoma) oncoproteins are constitutively active tyrosine kinases found in thyroid papillary carcinoma and nonneoplastic Hashimoto’s thyroiditis. Although several proteins have been identified to be substrates of RET/PTC kinases, the pathogenic roles played by RET/PTC in malignant and benign thyroid diseases and the molecular mechanisms that are involved are not fully understood. We found that RET/PTC expression phosphorylates the Y701 residue of STAT1, a type II interferon (IFN)-responsive protein. RET/PTC-mediated signal transducer and activator of transcription 1 (STAT1) phosphorylation requires RET/PTC kinase activity to be intact but other tyrosine kinases, such as Janus kinases or c-Src, are not involved. RET/PTC-induced STAT1 transcriptional activation was not inhibited by suppressor of cytokine signaling-1 or -3, or protein inhibitors of activated STAT3 [(protein inhibitor of activated STAT (PIAS3)], but PIAS1 strongly repressed the RET/PTC-induced transcriptional activity of STAT1. RET/PTC-induced STAT1 activation caused IFN regulatory factor-1 expression. We found that STAT1 and IFN regulatory factor-1 cooperated to significantly increase transcription from type IV IFN-γresponsive promoters of class II transactivator genes. Significantly, cells stably expressing RET/PTC expressed class II transactivator and showed enhanced de novo membrane expression of major histocompatibility complex (MHC) class II proteins. Furthermore, RET/PTC1-bearing papillary thyroid carcinoma cells strongly expressed MHC class II (human leukocyte-associated antigen-DRα) genes, whereas the surrounding normal tissues did not. Thus, RET/PTC is able to phosphorylate and activate STAT1. This may lead to enhanced MHC class II expression, which may explain why the tissues surrounding RET/PTC-positive cancers are infiltrated with lymphocytes. Such immune response-promoting activity of RET/PTC may also relate to the development of Hashimoto’s thyroiditis.