bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Validation of Colorectal Neoplasia–Specific Methylation Markers for Accurate Classification of Disease
Authors: Model Fabian , Osborn Neal , Ahlquist David , Gruetzmann Robert , Molnar Bela , Sipos Ferenc , Galamb Orsolya , Pilarsky Christian , Saeger Hans-Detlev , Tulassay Zsolt , Hale Kari , Mooney Suzanne , Lograsso Joseph , Adorjan Peter , Lesche Ralf , Dessauer Andreas , Kleiber Joerg , Porstmann Baerbel , Sledziewski Andrew , Lofton-Day Catherine 
Published: February 2007

AbstractAberrant DNA methylation occurs early in oncogenesis, is stable, and can be assayed in tissues and body fluids. Therefore, genes with aberrant methylation can provide clues for understanding tumor pathways and are attractive candidates for detection of early neoplastic events. Identification of sequences that optimally discriminate cancer from other diseased and healthy tissues is needed to advance both approaches. Using well-characterized specimens, genome-wide methylation techniques were used to identify candidate markers specific for colorectal neoplasia. To further validate 30 of these candidates from genome-wide analysis and 13 literature-derived genes, including genes involved in cancer and others with unknown functions, a high-throughput methylation-specific oligonucleotide microarray was used. The arrays were probed with bisulfite-converted DNA from 89 colorectal adenocarcinomas, 55 colorectal polyps, 31 inflammatory bowel disease, 115 extracolonic cancers, and 67 healthy tissues. The 20 most discriminating markers were highly methylated in colorectal neoplasia (area under the receiver operating characteristic curve &gt; 0.8; P &lt; 0.0001). Normal epithelium and extracolonic cancers revealed significantly lower methylation. Real-time PCR assays developed for 11 markers were tested on an independent set of 149 samples from colorectal adenocarcinomas, other diseases, and healthy tissues. Microarray results could be reproduced for 10 of 11 marker assays, including eight of the most discriminating markers (area under the receiver operating characteristic curve &gt; 0.72; P &lt; 0.009). The markers with high specificity for colorectal cancer have potential as blood-based screening markers whereas markers that are specific for multiple cancers could potentially be used as prognostic indicators, as biomarkers for therapeutic response monitoring or other diagnostic applications, compelling further investigation into their use in clinical testing and overall roles in tumorigenesis. (Mol Cancer Res 2007;5(2):153–63)
Nuclear Localization of the Parafibromin Tumor Suppressor Protein Implicated in the Hyperparathyroidism-Jaw Tumor Syndrome Enhances Its Proapoptotic Function
Authors: Lin Ling , Czapiga Meggan , Nini Lylia , Zhang Jian-Hua , Simonds William F. 
Published: February 2007

Abstract
Parafibromin is a tumor suppressor protein encoded by HRPT2, a gene recently implicated in the hereditary hyperparathyroidism-jaw tumor syndrome, parathyroid cancer, and a subset of kindreds with familial isolated hyperparathyroidism. Human parafibromin binds to RNA polymerase II as part of a PAF1 transcriptional regulatory complex. The mechanism by which loss of parafibromin function can lead to neoplastic transformation is poorly understood. Because the subcellular localization of parafibromin is likely to be critical for its function with the nuclear PAF1 complex, we sought to experimentally define the nuclear localization signal (NLS) of parafibromin and examine its potential role in parafibromin function. Using site-directed mutagenesis, we define a dominant bipartite NLS and a secondary NLS, both in the NH2-terminal region of parafibromin whose combined mutation nearly abolishes nuclear targeting. The NLS-mutant parafibromin is significantly impaired in its association with endogenous Paf1 and Leo1. We further report that overexpression of wild-type but not NLS-mutant parafibromin induces apoptosis in transfected cells. Inhibition of endogenous parafibromin expression by RNA interference inhibits the basal rate of apoptosis and apoptosis resulting from DNA damage induced by camptothecin, a topoisomerase I inhibitor. These experiments identify for the first time a proapoptotic activity of endogenous parafibromin likely to be important in its role as a tumor suppressor and show a functional role for the NLS of parafibromin in this activity. (Mol Cancer Res 2007;5(2):183–93)
Roscovitine Inhibits Differentiation and Invasion in a Three-Dimensional Skin Reconstruction Model of Metastatic Melanoma
Authors: Mohapatra Subhra , Coppola Domenico , Riker Adam I. , Pledger W. Jack 
Published: February 2007

AbstractThe aim of this study was to investigate the therapeutic potential of a cyclin-dependent kinase inhibitor, roscovitine, in cultured melanoma cells and a three-dimensional skin reconstruction model of metastatic melanoma. The modulatory effects of roscovitine on the growth and survival of normal melanocytes and cultured melanoma cell lines were tested. Additionally, we investigated the potential of roscovitine to regulate the growth and differentiation of a metastatic melanoma cell line (A375) in a three-dimensional skin reconstruction culture consisting of A375 cells admixed with normal human keratinocytes embedded within a collagen-constricted fibroblast matrix. We show that roscovitine is able to induce apoptosis in the melanoma cell lines A375, 888, and 624 but not in normal human cultured epithelial melanocytes. The degree of apoptosis within these cell lines correlated with the accumulation of p53 protein and concomitant reduction of X-linked inhibitor of apoptosis protein, with no change in the proteins Bcl-2 and survivin. We also found that roscovitine inhibited the growth and differentiation of A375 melanoma cells within the dermal layer of the skin. The results of this study show that roscovitine has the potential to inhibit the differentiation and invasion of metastatic melanoma and may be useful as a therapy for the treatment of patients with metastatic melanoma. (Mol Cancer Res 2007;5(2):145–51)
The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis
Authors: Karamouzis Michalis V. , Konstantinopoulos Panagiotis A. , Papavassiliou Athanasios G. 
Published: February 2007

AbstractRespiratory epithelium cancers are the leading cause of cancer-related death worldwide. The multistep natural history of carcinogenesis can be considered as a gradual accumulation of genetic and epigenetic aberrations, resulting in the deregulation of cellular homeostasis. Growing evidence suggests that cross-talk between membrane and nuclear receptor signaling pathways along with the activator protein-1 (AP-1) cascade and its cofactor network represent a pivotal molecular circuitry participating directly or indirectly in respiratory epithelium carcinogenesis. The crucial role of AP-1 transcription factor renders it an appealing target of future nuclear-directed anticancer therapeutic and chemoprevention approaches. In the present review, we will summarize the current knowledge regarding the implication of AP-1 proteins in respiratory epithelium carcinogenesis, highlight the ongoing research, and consider the future perspectives of their potential therapeutic interest. (Mol Cancer Res 2007;5(2):109–20)
G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms
Authors: Donini Marta , Fontana Stefania , Savoldi Gianfranco , Vermi William , Tassone Laura , Gentili Francesca , Zenaro Elena , Ferrari Daniela , Notarangelo Lucia D. , Porta Fulvio , Facchetti Fabio , Notarangelo Luigi D. , Dusi Stefano , Badolato Raffaele 
Published: February 2007

AbstractThe treatment of children affected by severe congenital neutropenia (SCN) with G-CSF strongly reduces the risk of sepsis by reversing neutropenia. However, SCN patients who respond to the treatment with the growth factor still have an elevated risk of succumbing to sepsis. Because the disease is usually caused by heterozygous mutations of ELA2, a gene encoding for neutrophil elastase (NE), we have investigated in G-CSF–responder and nonresponder patients affected by SCN the expression of polypeptides that constitute the antimicrobial machinery of these cells. In peripheral blood–derived neutrophils of patients with heterozygous mutations of ELA2 who were treated with G-CSF, NE was nearly absent as detected by immunofluorescence and immunoblotting, suggesting that production of the mutant protein interferes with normal gene expression. This defect was associated with abnormal expression of other granule-associated proteins such as myeloperoxidase, lactoferrin, cathepsin G, and human-neutrophil-peptide. Moreover, in one patient with partial response to G-CSF, we observed an impairment of neutrophil antimicrobial activity against Candida albicans, and, to a lower extent against Escherichia coli. Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients.
The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro
Authors: Newland Stephen A. , Macaulay Iain C. , Floto Andres R. , de Vet Edwin C. , Ouwehand Willem H. , Watkins Nicholas A. , Lyons Paul A. , Campbell Duncan R. 
Published: February 2007

AbstractThe G6B cell-surface receptor, which contains a single Ig-like domain, has been shown to bind to SHP-1 and SHP-2 after phosphorylation of 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail, classifying this protein as a new member of the family of inhibitory receptors. In this study, we demonstrate by real-time polymerase chain reaction (PCR) and Western-blot analysis that G6B is expressed on platelets. Cross-linking of G6B with polyclonal antisera has a significant inhibitory effect on platelet aggregation and activation by agonists such as ADP and collagen-related peptide (CRP). This inhibitory function of G6B appears to operate in a calcium-independent manner. Our results suggest that G6B represents a novel inhibitory receptor found on the surface of platelets and that it could be an antithrombotic drug target.
A neonatal presentation of factor V deficiency: A case report
Authors: Chingale Amol , Eisenhut Michael , Gadiraju Anjali , Liesner Ri 
Published: February 2007

Abstract

Background
Factor V deficiency is a rare autosomal recessive coagulation disorder. Awareness of presenting features and management is important to avoid bleeding complications associated with mortality and neurodisability.

Case presentation
A 6-day-old Pakistani boy was admitted with bleeding from the left nipple. His parents were first cousins. A coagulation screen showed a prothrombin time of 41 s (control 14 s), a partial thromboplastin time of 132 s (control 33 s) and a normal thrombin time of 15 s (control 14 s). Factor V activity was <0.01 IU/ml. Oral tranexamic acid was started. At 5 weeks of age the child presented with irritability, lethargy and reduced feeding and a drop of hemoglobin to 5.6 g/dl. A cranial computed tomography scan showed a right intra-cerebral bleed extending from the frontal lobe to the parieto-occipital region with shift of the midline to the left. A regime of 20 ml/kg of fresh frozen plasma four times a week was instituted and has prevented further bleeds up to the present age of 21 months. Neurodevelopment remained normal.

Conclusion
This case illustrates that in an unusually bleeding newborn of consanguineous parents rare severe homozygous bleeding disorders need to be considered. Nipple bleeding may be the first presentation of a congenital bleeding disorder. In cases of factor V deficiency where factor concentrates are not available long term use of fresh frozen plasma can prevent potentially life threatening bleeding.
Selective serotonin reuptake inhibitor use associates with apathy among depressed elderly: a case-control study
Authors: Wongpakaran Nahathai , van Reekum Robert , Wongpakaran Tinakon , Clarke Diana 
Published: February 2007

Abstract

Background
It has been reported for over the past decade that the use of selective serotonin reuptake inhibitors (SSRI's) may associate with the emergence of apathy. The authors hypothesized that depressed patients treated with SSRI's would show more signs of apathy than patients treated with non-SSRI antidepressants. This case control study was conducted to investigate the possibility of the association between SSRI use and the occurrence of apathy.

Methods
Baycrest Centre for Geriatric Care's Day Hospital Database of elderly depressed patients who received antidepressants was divided into 2 groups depending on antidepressant use at discharge: SSRI user group-SUG, and non-SSRI user group-NSUG. Apathy scales developed by the authors were selected from the Geriatric depression Scale (GDS) and the Hamilton Rating Scale for Depression (HAMD), and were titled as GDS-apathy subscale (GAS) and HAMD-apathy subscale (HAS). Demographic data, baseline apathy, underlying medical conditions and medication use were studied. Proportion, analysis of variances, Chi-square test, odds ratio with 95% confidence interval were reported.

Results
Among 384 patients (160 SUG and 224 NSUG), mean GDS and HAM-D at discharge were 12.46 and 10.61 in SUG, and were 11.37 and 9.30 in NSUG, respectively. Using GAS for apathy assessment, 83.7% of patients in SUG and 73.4% in NSUG stayed apathetic at discharge. As evaluated by HAS, 44.2% of patients in SUG and 36.5% in NSUG stayed apathetic. SSRI use was not a predictor of apathy at admission, while it was at discharge, p = 0.029. The SUG showed more patients with apathy than that found in NSUG (adjusted OR = 1.90 (1.14–3.17). Age 70–75 years tended to be a predictor for the apathy (p = 0.058). Using HAS, age 70–75 years and living situation were associated with apathy at discharge, p = 0.032 and 0.038 respectively.

Conclusion
Even though depression was improved in elderly patients receiving antidepressants, apathy appeared to be greater in patients who were treated with SSRI than that found in patients who were not. Frontal lobe dysfunction due to alteration of serotonin is considered to be one of the possibilities.
Ineffectiveness of Rosiglitazone Therapy in Nelson’s Syndrome
Authors: Munir A. , Song F. , Ince P. , Walters S. J. , Ross R. , Newell-Price J. 
Published: February 2007

Abstract
Background: Peroxisome proliferator-activated receptor (PPAR)-γ agonists have been proposed as therapy to lower plasma ACTH in Cushing’s disease. Cyclical secretion of ACTH may, however, explain some of the responses seen. Patients with Nelson’s syndrome have persistently high levels of ACTH and may be a better model for examining new therapies to elevated ACTH levels.
Objective: The objective of the study was to assess whether high-dose rosiglitazone therapy reduces circulating ACTH levels in Nelson’s syndrome, a model of ACTH hypersecretion for which no established medical therapy exists.
Design: The design was an open-label, prospective, nonrandomized study over 14 wk.
Setting: The study was conducted at a university teaching hospital.
Patients: Six patients with Nelson’s syndrome participated in the study.
Methods: Patients were assessed at −2, 0, 4, 8, and 12 wk. Rosiglitazone 12 mg/d was administered between 0 and 8 wk. PPAR-γ immunoreactivity was assessed in pathological tissue.
Outcome Measure: Plasma ACTH was measured before (0830 h) and 120 min after morning dosing with hydrocortisone (HC).
Results: One female withdrew prior to commencing therapy for personal reasons. There was no evidence that ACTH levels changed over time (P = 0.864). The average ACTH level was 1187 ng/liter (95% confidence interval 928–1446) for patients before the HC dose and 432 ng/liter (95% confidence interval 172–692) after the HC dose. PPAR-γ immunoreactivity was positive in three ACTH-secreting tumors available.
Conclusions: Rosiglitazone 12 mg/d did not change circulating ACTH over time, despite PPAR-γ receptor expression in the tumor tissue. However, this does not preclude the possibility that other patients may respond or that higher doses of rosiglitazone or more potent agonists might prove useful treatment.
Healthcare Outcomes Associated with Beers' Criteria: A Systematic Review
Authors: Jano Elda , Aparasu Rajender R 
Published: February 2007

Objective: To examine healthcare outcomes associated with Beers' criteria of inappropriate medication use based on a literature review. Data Sources: A search of MEDLINE, International Pharmaceutical Abstracts, and Cumulative Index to Nursing and Allied Health Literature was conducted to identify articles published from October 1991 to October 2006. The following key words were used: Beers, inappropriate, medication, drug, use, prescribing, and elderly. A manual search was also conducted using the references listed in the articles identified through the database search. Study Selection And Data Extraction: Studies that examined the impact or outcomes of Beers' criteria of inappropriate medication use (1991, 1997, and 2003 critera) were selected. Each article was examined for study setting, data source, study sample, study design, criteria, analysis and covariates, type of healthcare outcome, and study findings. Of 235 articles retrieved, 18 presented studies that examined healthcare outcomes associated with inappropriate medication use based on Beers' criteria. Specifically, setting-specific evidence as well as overall evidence was examined from the selected studies. The review considered evidence of association if more than 50% of the findings were statistically significant. Data Synthesis: Most of the 18 studies evaluated were retrospective cohort studies involving patients 65 years of age or older from diverse healthcare settings. In community settings, there was no evidence of association with respect to mortality and other healthcare use, and evidence regarding quality of life and costs was inconclusive. However, inappropriate medication use was associated with hospitalization measures in community elderly. In nursing homes, there was no evidence of association with mortality and the association with hospitalization measures was inconclusive. In hospitals, there was inconclusive evidence to make any generalizations. Across healthcare settings, inappropriate medication use was associated with adverse drug reactions and costs but not with other outcome measures. Conclusions: There is evidence that Beers' criteria of inappropriate medication use is associated with adverse healthcare impact in the community-dwelling elderly. With increasing use of Beers' criteria as quality-of-care measures, there is a need to strengthen the predictive validity of these criteria in all healthcare settings.
Heat shock protein 70-1 gene expression in pediatric heart surgery using blood cardioplegia
Authors: Vittorini Simona , Storti Simona , Andreani Giovanna , Giusti Lauro , Murzi Bruno , Furfori Pierantonio , Baroni Alessandra , Lucia Vittoria De , Luisi Vincenzo Stefano , Clerico Aldo 
Published: February 2007

AbstractClin Chem Lab Med 2007;45:244–8.
Biochemical reference intervals for sex hormones with a new AutoDelfia method in aged men
Authors: Eskelinen Seija , Vahlberg Tero , Isoaho Raimo , Kivelä Sirkka-Liisa , Irjala Kerttu 
Published: February 2007

AbstractOur aim was to establish sex hormone reference intervals measured with a new AutoDelfia immunoassay method for aged men free of medication and/or conditions known to influence sex hormone levels.The reference population consisted of 466 individuals between 64 and 97 years (mean 72 years) and a mean body mass index (BMI) of 26.9 kg/mBecause age correlated significantly with most sex hormones studied, we calculated reference intervals for three age groups (64–69, 70–74 and ≥75 years). In clinical practice, single ranges can be used for men aged 64 years or over for testosterone, estradiol and follicle-stimulating hormone (FSH) with the AutoDelfia method. For free testosterone and luteinizing hormone (LH), separate reference intervals should be used for men aged 64–74 years and those aged 75 years or over. For sex hormone-binding globulin, two separate reference intervals by age (64–69 and ≥70 years) are also needed for aged men. LH and FSH reference ranges should be judged with caution, because they may be too high due to cases of subclinical hypogonadism included in the reference population.Clin Chem Lab Med 2007;45:249–53.
Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily
Authors: Stella Giuseppe , Spada Rosario Sebastiano , Calabrese Santa , Bosco Paolo , Anello Guido , Guéant-Rodriguez Rosa-Maria , Romano Antonino , Benamghar Lahoucine , Proto Caterina , Castellano Antonino , Fajardo Adrian , Lipari Lina , Sirna Salvatore , Guéant Jean-Louis 
Published: February 2007

AbstractAssociation of thyroid dysfunction with plasma homocysteine levels and vitamin BSubjects (n=279) aged 60–85 years (119 males and 160 females) were examined using self-reported signs, clinical examination and laboratory tests.Hypothyroidism and/or goiter were two characteristics that were not associated with a significant change in homocysteine when compared with euthyroidism and the absence of goiter. Vitamin BOur results suggest that the influence of thyroid hormones on homocysteine is much weaker in elderly subjects than in selected patients with hypothyroidism.Clin Chem Lab Med 2007;45:143–7.
Prospective Evaluation of the AM-PAC-CAT in Outpatient Rehabilitation Settings
Authors: Jette Alan M , Haley Stephen M , Tao Wei , Ni Pengsheng , Moed Richard , Meyers Doug , Zurek Matthew 
Published: February 2007

Background and PurposeThe purpose of this study was to prospectively evaluate the practical and psychometric adequacy of the Activity Measure for Post-Acute Care (AM-PAC) “item bank” and computerized adaptive testing (CAT) assessment platform (AM-PAC-CAT) when applied within orthopedic outpatient physical therapy settings.MethodThis was a prospective study with a convenience sample of 1,815 patients with spine, lower-extremity, or upper-extremity impairments who received outpatient physical therapy in 1 of 20 outpatient clinics across 5 states. The authors conducted an evaluation of the number of items used and amount of time needed to complete the CAT assessment; evaluation of breadth of content coverage, item exposure rate, and test precision; as well as an assessment of the validity and sensitivity to change of the score estimates.ResultsOverall, the AM-PAC-CAT's Basic Mobility scale demonstrated excellent psychometric properties while the Daily Activity scale demonstrated less adequate psychometric properties when applied in this outpatient sample. The mean length of time to complete the Basic Mobility scale was 1.9 minutes, using, on average, 6.6 items per CAT session, and the mean length of time to complete the Daily Activity scale was 1.01 minutes, using on average, 6.8 items.Background and ConclusionOverall, the findings are encouraging, yet they do reveal several areas where the AM-PAC-CAT scales can be improved to best suit the needs of patients who are receiving outpatient orthopedic physical therapy of the type included in this study.