bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells
Authors: Sakimura Riku , Tanaka Kazuhiro , Yamamoto Syunsaku , Matsunobu Tomoya , Li Xu , Hanada Masuo , Okada Takamitsu , Nakamura Tomoyuki , Li Yang , Iwamoto Yukihide 
Published: January 2007

Abstract
Purpose: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas.
Experimental Design: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth of chondrosarcoma cell lines. We also investigated the modulation of the expression levels of extracellular matrix genes and the induction of phenotypic change in chondrosarcoma cells treated with depsipeptide. Finally, we examined the antitumor effect of depsipeptide on chondrosarcoma in vivo.
Results: Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle arrest and/or apoptosis. HDAC inhibitors increased the expression of the α1 chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation in the promoter and enhancer. Depsipeptide also up-regulated the expressions of aggrecan and the α2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner. Moreover, long-term treatment with a low dose of depsipeptide resulted in the induction of differentiation into hypertrophic phenotype, as shown by the increment of the α1 chain of type X collagen (COL10A1) expression in chondrosarcoma cells. In vivo studies and histologic analyses confirmed that depsipeptide significantly inhibited tumor growth and induced differentiation into the hypertrophic and mineralized state in chondrosarcoma cells.
Conclusions: These results strongly suggest that HDAC inhibitors may be promising reagents for use as a differentiating chemotherapy against chondrosarcomas.
Therapeutic Synergy of Human Papillomavirus E7 Subunit Vaccines plus Cisplatin in an Animal Tumor Model: Causal Involvement of Increased Sensitivity of Cisplatin-Treated Tumors to CTL-Mediated Killing in Therapeutic Synergy
Authors: Bae Sung Hwa , Park Young-Ja , Park Jae-Bok , Choi Youn Seok , Kim Mi Suk , Sin Jeong-Im 
Published: January 2007

AbstractPurpose: The goal of this study was to investigate the therapeutic potentials of combining chemotherapy with human papillomavirus (HPV) E7 subunit vaccines in an animal tumor model and to determine the underlying therapeutic mechanisms.Experimental Design: Animals bearing HPV E6/E7–expressing tumors were treated intratumorally with a selected cytotoxic drug, cisplatin, twice at 1-week interval and s.c. with E7 subunit vaccines thrice at 1-week interval. Tumor chemoimmunoresponse was measured by tumor size. Ag-specific CTL activities and tumor histology were checked in mice under treatments. Apoptosis, in vivo T-cell subset depletion, adoptive CTL transfer, and tumor regression were used to determine the mechanisms for antitumor therapeutic effects.Results: Combined therapy using cisplatin plus E7 subunit vaccines improved cure and recurrence rates of tumors and long-term antitumor immunity dramatically more than single therapy alone. In particular, both components of E7 subunit vaccines were required for induction of Ag-specific CTL as well as therapeutic synergy when combined with cisplatin. This therapeutic synergy was abrogated by depletion of CD8+ T cells in vivo and was concomitant with histologic changes (such as heavy infiltration of lymphocytes and reduced tumor cell density). Finally, the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing was found to be responsible for therapeutic synergy.Conclusions: E7 subunit vaccines plus cisplatin mediate antitumor therapeutic synergy through the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing. Moreover, E7-based therapeutic vaccines have the potential to improve chemotherapy in patients with cervical cancer.
Gene-Expression and Immunohistochemical Study of Specific T-Cell Subsets and Accessory Cell Types in the Transformation and Prognosis of Follicular Lymphoma
Authors: Glas Annuska M. , Knoops Laurent , Delahaye Leonie , Kersten Marie José , Kibbelaar Robby E. , Wessels Lodewyk A. , van Laar Ryan , van Krieken J. Han J.M. , Baars Joke W. , Raemaekers John , Kluin Philip M. , van ’t Veer Laura J. , de Jong Daphne 
Published: January 2007

PurposeDespite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis—with death within 3 years of diagnosis—most often due to transformation to aggressive disease.Patients and MethodsIn this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis.ResultsAt the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting. Combinations of differentially expressed genes indicate that immunologic mechanisms play a differential role in the risk of early transformation. Using immunohistochemistry for specific cell populations, the spatial distribution to neoplastic follicles and the activation of CD4–positive T-helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be highly discriminatory to predict early transformation. A role for functional modulation of follicular dendritic cells could also be supported (P = .04). Other cell populations, including CD68-positive macrophages and regulatory T cells, were not differentially present.ConclusionThese results support the identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior.
Five Years of Letrozole Compared With Tamoxifen As Initial Adjuvant Therapy for Postmenopausal Women With Endocrine-Responsive Early Breast Cancer: Update of Study BIG 1-98
Authors: Coates Alan S. , Keshaviah Aparna , Thürlimann Beat , Mouridsen Henning , Mauriac Louis , Forbes John F. , Paridaens Robert , Castiglione-Gertsch Monica , Gelber Richard D. , Colleoni Marco , Láng István , Del Mastro Lucia , Smith Ian , Chirgwin Jacquie , Nogaret Jean-Marie , Pienkowski Tadeusz , Wardley Andrew , Jakobsen Erik H. , Price Karen N. , Goldhirsch Aron 
Published: January 2007

Purpose Previous analyses of the Breast International Group (BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results. Patients and Methods Four thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point. Results At a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women receiving tamoxifen. This reflected an 18% reduction in the risk of an event (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .007). No predefined subsets showed differential benefit. Adverse events were similar to previous reports. Patients on tamoxifen experienced more thromboembolic events, endometrial pathology, hot flashes, night sweats, and vaginal bleeding. Patients on letrozole experienced more bone fractures, arthralgia, low-grade hypercholesterolemia, and cardiovascular events other than ischemia and cardiac failure. Conclusion The present updated analysis, which was limited to patients on monotherapy arms in BIG 1-98, yields results similar to those from the previous primary analysis but more directly comparable with results from other trials of continuous therapy using a single endocrine agent.
Association between Blood Pressure and Serum Thyroid-Stimulating Hormone Concentration within the Reference Range: A Population-Based Study
Authors: Åsvold Bjørn O. , Bjøro Trine , Nilsen Tom I. L. , Vatten Lars J. 
Published: January 2007

Abstract
Context: The association between thyroid function and blood pressure is insufficiently studied.
Objective: The objective of the investigation was to study the association between TSH within the reference range and blood pressure.
Design and Setting: This was a cross-sectional, population-based study.
Subjects: A total of 30,728 individuals without previously known thyroid disease were studied.
Main Outcome Measures: The main outcome measures were mean systolic and diastolic blood pressure and pulse pressure and odds ratio for hypertension (&gt;140/90 mm Hg or current or previous use of antihypertensive medication), according to categories of TSH.
Results: Within the reference range of TSH (0.50–3.5 mU/liter), there was a linear increase in blood pressure with increasing TSH. The average increase in systolic blood pressure was 2.0 mm Hg [95% confidence interval (CI) 1.4–2.6 mm Hg] per milliunit per liter increase in TSH among men, and 1.8 mm Hg (95% CI 1.4–2.3 mm Hg) in women. The corresponding increase in diastolic blood pressure was 1.6 mm Hg (95% CI 1.2–2.0 mm Hg) in men and 1.1 mm Hg (95% CI 0.8–1.3 mm Hg) in women. Comparing TSH of 3.0–3.5 mU/liter (upper part of the reference) with TSH of 0.50–0.99 mU/liter (lower part of the reference), the odds ratio for hypertension was 1.98 (95% CI 1.56–2.53) in men and 1.23 (95% CI 1.04–1.46) in women.
Conclusion: Within the reference range of TSH, we found a linear positive association between TSH and systolic and diastolic blood pressure that may have long-term implications for cardiovascular health.
Clopidogrel-Precipitated Rhabdomyolysis in a Stable Heart Transplant Patient
Authors: Burton Jeffrey R , Burton Ilene , Pearson Glen J 
Published: January 2007

Objective: To report the case of an orthotopic heart transplant recipient who developed rhabdomyolysis precipitated by the addition of clopidogrel to the existing regimen of cyclosporine and atorvastatin, which had been tolerated for more than 3 years without adverse effects or laboratory evidence of myositis. Case Summary: Fourteen years after cardiac transplantation, a 58-year-old woman began a planned 4 week course of clopidogrel 75 mg/day following coronary angioplasty and placement of a stent in the left circumflex coronary artery. Almost 4 weeks later, she presented with severe muscle pain and weakness and laboratory evidence of rhabdomyolysis, with marked elevations of plasma creatine kinase (96 000 U/L) and urine myoglobin (332 872 μg/L.) as well as early acute renal failure (serum creatinine 2.9 mg/dL). Symptoms and laboratory abnormalities resolved with cessation of cyclosporine, atorvastatin, and clopidogrel. Clopidogrel was not restarted, while atorvastatin and cyclosporine were; the patient had no recurrence of symptoms up to 15 months later. Discussion: Both atorvastatin and cyclosporine, as well as clopidogrel's active thiol derivative, are metabolized by the cytochrome P450 3A4 isoenzyme. Cyclosporine is also a moderate inhibitor of this isoenzyme. We postulate that competition between atorvastatin and clopidogrel for CYP3A4 receptors, already partially inhibited by cyclosporine, led to increased atorvastatin concentrations, resulting in the acute onset of rhabdomyolysis. This theory is further supported by the patient's continued ability to tolerate the combination of atorvastatin and cyclosporine, without clopidogrel, on rechallenge. Use of the Naranjo probability scale revealed that rhabdomyolysis was probably precipitated by the addition of clopidogrel to the stable baseline regimen of cyclosporine and atorvastatin. Conclusions: Practitioners must be conscious of the potential for adverse effects when prescribing clopidogrel to heart transplant patients who are concomitantly receiving cyclosporine and a statin. If concomitant administration is required, careful clinical and laboratory monitoring of the patient is necessary.
Caregiver Health Literacy and the Use of Child Health Services
Authors: Sanders Lee M. , Thompson Valerie T. , Wilkinson James D. 
Published: January 2007

OBJECTIVES. Eighty million US adults have low health literacy, a risk factor for increased health care use among adults. The purpose of this work was to assess the association between caregiver health literacy and the use and cost of child health services.METHODS. We conducted a cross-sectional study of caregiver-child dyads from a sample of children aged 12 months to 12 years presenting to the pediatric emergency department of an urban, public hospital. Caregiver health literacy was measured by the Short Test of Functional Health Literacy in their preferred language (English or Spanish). Child health care use was measured by a 12-month retrospective review of the public hospital system's electronic database and of state Medicaid billing records for 4 types of visits: preventive care, urgent care, emergency care, and hospital care. Cost of child health care use was provided by Medicaid billing records. Multivariate analysis included caregiver education, age, and language proficiency, as well as child age, special health care needs, ethnicity, and health-insurance coverage.RESULTS. A total of 290 dyads were enrolled in the study. Twenty-two percent of caregivers had low (inadequate or marginal) health literacy. Caregivers with low health literacy were more likely to have less than a high school education, to have limited English proficiency, and to have been born outside the United States. There were no differences in health care use or cost between children of caregivers with low health literacy and children of caregivers with adequate health literacy. Three caregiver characteristics were associated with increased use of child health care services: born outside the United States, age at child’s birth &lt;24 years, and limited English proficiency.CONCLUSIONS. One in 5 caregivers of young children has low health literacy. Caregiver health literacy, however, was not associated with disparities in the use of child health services in this inner-city, ethnic minority population.
Adolescent Depression Screening in Primary Care: Feasibility and Acceptability
Authors: Zuckerbrot Rachel A. , Maxon Laura , Pagar Dana , Davies Mark , Fisher Prudence W. , Shaffer David 
Published: January 2007

OBJECTIVE. Despite available depression treatments, only one fourth to one third of depressed adolescents are receiving care. The problem of underdiagnosis and underreferral might be redressed if assessment of suicidality and depression became a more formal part of routine pediatric care. Our purpose for this study was to explore the feasibility and acceptability of implementing adolescent depression screening into clinical practice.METHODS. In this study we implemented a 2-stage adolescent identification protocol, a first-stage pen-and-paper screen and a second-stage computerized assessment, into a busy primary care pediatric practice. Providers tracked the number of eligible patients screened at both health maintenance and urgent care visits and provided survey responses regarding the burden that screening placed on the practice and the effect on patient/parent-provider relationships.RESULTS. Seventy-nine percent of adolescent patients presenting for health maintenance visits were screened, as were the majority of patients presenting for any type of visit. The average completion time for the paper screen was 4.6 minutes. Providers perceived parents and patients as expressing more satisfaction than dissatisfaction with the screening procedures and that the increased time burden could be handled. All providers wished to continue using the paper screen at the conclusion of the protocol.CONCLUSIONS. Instituting universal systematic depression screening in a practice with a standardized screening instrument met with little resistance by patients and parents and was well perceived and accepted by providers.
A Randomized, Controlled Trial of Heparin Versus Placebo Infusion to Prolong the Usability of Peripherally Placed Percutaneous Central Venous Catheters (PCVCs) in Neonates: The HIP (Heparin Infusion for PCVC) Study
Authors: Shah Prakesh S. , Kalyn Angela , Satodia Prakash , Dunn Michael S. , Parvez Boriana , Daneman Alan , Salem Shia , Glanc Phyllis , Ohlsson Arne , Shah Vibhuti 
Published: January 2007

BACKGROUND. Mechanical and infectious complications shorten the effective duration of peripherally inserted central venous catheters. Heparin use to prevent such complications and prolong the usability of peripherally inserted central venous catheters is inconclusive.OBJECTIVE. Our goal was to evaluate the effectiveness of heparin in prolonging the usability of peripherally inserted central venous catheters in neonates.DESIGN/METHODS. We performed a multicenter, randomized, controlled trial of heparin infusion (0.5 U/kg per hour) versus placebo for peripherally inserted central venous catheters in neonates. The primary outcome was duration of catheter use. Secondary outcomes were occlusion, catheter-related sepsis, thrombosis, and adverse effects of heparin. To detect a 168-hour (1-week) difference in the duration of catheter use, 192 patients were needed. Kaplan-Meier and Cox regression analyses were performed.RESULTS. A total of 201 neonates were enrolled (heparin group: n = 100; control group: n = 101). Baseline demographics were similar between the groups. Duration of catheter use was longer in the infants in the heparin versus the placebo group. Study center, gender, birth weight, and type and position of the catheter were not predictors of duration of catheter use. For those in the heparin versus the placebo group, the incidence of elective catheter removal (therapy completed) was 63% vs 42%, of occlusion was 6% vs 31%, of thrombosis was 20% vs 21%, and of catheter-related sepsis was 10% vs 6%, respectively. No adverse events were noted.CONCLUSIONS. Heparin infusion prolonged the duration of peripherally inserted central venous catheter usability, which permitted a higher percentage of neonates to complete therapy without increasing adverse effects.
Breastfeeding and Infant Eczema in the First Year of Life in the KOALA Birth Cohort Study: A Risk Period–Specific Analysis
Authors: Snijders Bianca E. P. , Thijs Carel , Kummeling Ischa , Penders John , van den Brandt Piet A. 
Published: January 2007

OBJECTIVE. We studied the association between breastfeeding and eczema, taking into account the possible influence of reverse causation, with risk period–specific analyses.
METHODS. Information on breastfeeding, determinants, and outcomes at 1 year of age was collected with repeated questionnaires for 2405 mother-infant pairs participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) birth cohort study. By using multivariate logistic regression analysis, we compared an overall analysis with risk period–specific analyses.
RESULTS. By the age of 1 year, 535 infants (22.2%) had developed eczema. In an overall analysis, we found a weak nonsignificant trend toward a reduced risk of eczema in the first year of life with increasing duration of breastfeeding (lowest risk for those breastfed for ≥7 months versus never breastfed). In the risk period–specific analysis (confined to infants “at risk” for eczema onset after 3 months of age), no indication for reverse causation was found (results were not very different, compared with the overall analysis). Infants who were breastfed from birth on had a slightly (although not statistically significantly) increased risk for eczema in the first 3 months of life, compared with infants who were formula fed from birth on.
CONCLUSIONS. Our results indicated that no strong effect of breastfeeding on eczema in the first year of life was present. This conclusion was strengthened by risk period–specific analysis, which made the influence of reverse causation unlikely.
Lactobacillus reuteri(American Type Culture Collection Strain 55730) Versus Simethicone in the Treatment of Infantile Colic: A Prospective Randomized Study
Authors: Savino Francesco , Pelle Emanuela , Palumeri Elisabetta , Oggero Roberto , Miniero Roberto 
Published: January 2007

OBJECTIVE. The goal was to test the hypothesis that oral administration of Lactobacillus reuteri in a prospective randomized study would improve symptoms of infantile colic.METHODS. Ninety breastfed colicky infants were assigned randomly to receive either the probiotic L reuteri (108 live bacteria per day) or simethicone (60 mg/day) each day for 28 days. The mothers avoided cow's milk in their diet. Parents monitored daily crying times and adverse effects by using a questionnaire.RESULTS. Eighty-three infants completed the trial: 41 in the probiotic group and 42 in the simethicone group. The infants were similar regarding gestational age, birth weight, gender, and crying time at baseline. Daily median crying times in the probiotic and simethicone groups were 159 minutes/day and 177 minutes/day, respectively, on the seventh day and 51 minutes/day and 145 minutes/day on the 28th day. On day 28, 39 patients (95%) were responders in the probiotic group and 3 patients (7%) were responders in the simethicone group. No adverse effects were reported.CONCLUSIONS. In our cohort, L reuteri improved colicky symptoms in breastfed infants within 1 week of treatment, compared with simethicone, which suggests that probiotics may have a role in the treatment of infantile colic.