bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ras Induces Chromosome Instability and Abrogation of the DNA Damage Response
Authors: Abulaiti Adili , Fikaris Aphrothiti J. , Tsygankova Oxana M. , Meinkoth Judy L. 
Published: November 2006

Abstract
Ras mutations are frequent in thyroid tumors, the most common endocrine malignancy. The ability of Ras to transform thyroid cells is thought to rely on its mitogenic activity. Unexpectedly, acute expression of activated Ras in normal rat thyroid cells induced a DNA damage response, followed by apoptosis. Notably, a subpopulation of cells evaded apoptosis and emerged with features of transformation, including the loss of epithelial morphology, dedifferentiation, and the acquisition of hormone- and anchorage-independent proliferation. Strikingly, the surviving cells showed marked chromosomal instability. Acutely, Ras stimulated replication stress as evidenced by the induction of ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) activity (Chk1 phosphorylation) and of γH2A.X, a marker of DNA damage. Despite the activation of a checkpoint, cells continued through mitosis in the face of DNA damage, resulting in an increase in cells harboring micronuclei, an indication of defects in chromosome segregation and other forms of chromosome damage. Cells that survived exposure to Ras continued to exhibit replication stress (ATR activation) but no longer exhibited γH2A.X or full activation of p53. When rechallenged with Ras or DNA-damaging agents, the surviving cells were more resistant to apoptosis than parental cells. These data show that acute expression of activated Ras is sufficient to induce chromosomal instability in the absence of other signals, and suggest that Ras-induced chromosomal instability arises as a consequence of defects in the processing of DNA damage. Hence, abrogation of the DNA damage response may constitute a novel mechanism for Ras transformation. (Cancer Res 2006; 66(21): 10505-12)
Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells
Authors: Yang Eric V. , Sood Anil K. , Chen Min , Li Yang , Eubank Tim D. , Marsh Clay B. , Jewell Scott , Flavahan Nicholas A. , Morrison Carl , Yeh Peir-En , Lemeshow Stanley , Glaser Ronald 
Published: November 2006

Abstract
Recent studies using ovarian cancer cells have shown that the catecholamine hormones norepinephrine (norepi) and epinephrine (epi) may influence cancer progression by modulating the expression of matrix metalloproteinases (MMP) and vascular endothelial growth factor (VEGF). The purpose of this study is to determine if the stress hormone norepi can influence the expression of MMP-2, MMP-9, and VEGF in nasopharyngeal carcinoma (NPC) tumors by using three NPC tumor cell lines. The NPC cell lines HONE-1, HNE-1, and CNE-1 were treated with norepi. The effects of norepi on MMP-2, MMP-9, and VEGF synthesis were measured by ELISA; functional MMP activity was measured by the invasive potential of the cells using a membrane invasion culture system whereas functional activity of VEGF was analyzed using a human umbilical vein endothelial cell tube formation assay. Norepi treatment increased MMP-2, MMP-9, and VEGF levels in culture supernatants of HONE-1 cells, which could be inhibited by the β-blocker propranolol. Norepi induced the invasiveness of all NPC cell lines in a dose-dependent manner, which was blocked by CMT-3, an MMP inhibitor, and propranolol. Norepi stimulated the release of functional angiogenic VEGF by HONE-1 cells as well. Finally, HONE-1 cells were shown to express β-adrenergic receptors as did seven of seven NPC biopsies examined. The data suggest that catecholamine hormones produced by the sympathetic-adrenal medullary axis may affect NPC tumor progression, in part, through modulation of key angiogenic cytokines. (Cancer Res 2006; 66(21): 10357-64)
ATM deficiency disrupts Tcra locus integrity and the maturation of CD4+CD8+ thymocytes
Authors: Matei Irina R. , Gladdy Rebecca A. , Nutter Lauryl M. J. , Canty Angelo , Guidos Cynthia J. , Danska Jayne S. 
Published: November 2006

AbstractMutations in ATM (ataxia-telangiectasia mutated) cause ataxia-telangiectasia (AT), a disease characterized by neurodegeneration, sterility, immunodeficiency, and T-cell leukemia. Defective ATM-mediated DNA damage responses underlie many aspects of the AT syndrome, but the basis for the immune deficiency has not been defined. ATM associates with DNA double-strand breaks (DSBs), and some evidence suggests that ATM may regulate V(D)J recombination. However, it remains unclear how ATM loss compromises lymphocyte development in vivo. Here, we show that T-cell receptor β (TCRβ)–dependent proliferation and production of TCRβlow CD4+CD8+ (DP) thymocytes occurred normally in Atm−/− mice. In striking contrast, the postmitotic maturation of TCRβlow DP precursors into TCRβint DP cells and TCRβhi mature thymocytes was profoundly impaired. Furthermore, Atm−/− thymocytes expressed abnormally low amounts of TCRα mRNA and protein. These defects were not attributable to the induction of a BCL-2–sensitive apoptotic pathway. Rather, they were associated with frequent biallelic loss of distal Va gene segments in DP thymocytes, revealing that ATM maintains Tcra locus integrity as it undergoes V(D)J recombination. Collectively, our data demonstrate that ATM loss increases the frequency of aberrant Tcra deletion events, which compromise DP thymocyte maturation and likely promote the generation of oncogenic TCR translocations.
Electron‐microscopic observations on the muscular coat of swell bodies in human nasal mucosa
Authors: Grevers G. 
Published: November 2006

AbstractMorphology and function of so‐called nasal “swell bodies” or “cavernous tissue ” have been studied by many investigators during the past 140 years. However, many details of this interesting and peculiar tissue remained unsolved, even though this vascular system plays an important role in a variety of rhinologic disorders. The present study describes electron‐microscopic details of the muscular coat of the different venous structures that form human nasal swell bodies. The specimens were taken from patients requiring removal of conchal mucosa and septoplasty; semithin and ultrathin sections were obtained and examined with the optical and electron microscopes. The histologic evaluation showed differences in the venous wall structure depending on the location of the vessels. The muscular layers were significantly thinner in those parts of the swell bodies located adjacent to the epithelium. Electron‐microscopic studies enabled us to determine the cytoplasmic components of smooth muscle cells, i.e., thin filaments, glycogen granules, caveolar plasmalemmal areas, cytoplasmic dense bodies (CDB), and membrane‐associated dense bodies (MADB). Another interesting feature was the varying appearance of the basal lamina of smooth muscle cells of the cavernous tissue. Based on the findings of the present study, the morphologic peculiarities of nasal swell bodies are compared and discussed with the appropriate literature. Further immunohistochemical and molecular‐biological studies will have to be performed to understand the complex functional mechanism of this unique vascular system.
Diabetes Mellitus Screening in Pediatric Primary Care
Authors: Anand Shikha G. , Mehta Supriya D. , Adams William G. 
Published: November 2006

OBJECTIVE. The goal was to determine the rates of diabetes screening and the prevalence of screening abnormalities in overweight and nonoverweight individuals in an urban primary care clinic.
METHODS. This study was a retrospective chart review conducted in a hospital-based urban primary care setting. Deidentified data for patients who were 10 to 19 years of age and had ≥1 BMI measurement between September 1, 2002, and September 1, 2004, were extracted from the hospital electronic health record.
RESULTS. A total of 7710 patients met the study criteria. Patients were 73.0% black or Hispanic and 47.0% female; 42.0% of children exceeded normal weight, with 18.2% at risk for overweight and 23.8% overweight. On the basis of BMI, family history, and race, 8.7% of patients met American Diabetes Association criteria for type 2 diabetes mellitus screening, and 2452 screening tests were performed for 1642 patients. Female gender, older age group, and family history of diabetes were associated with screening. Increasing BMI percentile was associated with screening, exhibiting a dose-response relationship. Screening rates were significantly higher (45.4% vs 19.0%) for patients who met the American Diabetes Association criteria; however, less than one half of adolescents who should have been screened were screened. Abnormal glucose metabolism was seen for 9.2% of patients screened.
CONCLUSIONS. This study shows that, although pediatricians are screening for diabetes mellitus, screening is not being conducted according to the American Diabetes Association consensus statement. Point-of-care delivery of consensus recommendations could increase provider awareness of current recommendations, possibly improving rates of systematic screening and subsequent identification of children with laboratory evidence of abnormal glucose metabolism.
Medication Errors Related to Computerized Order Entry for Children
Authors: Walsh Kathleen E. , Adams William G. , Bauchner Howard , Vinci Robert J. , Chessare John B. , Cooper Maureen R. , Hebert Pamela M. , Schainker Elisabeth G. , Landrigan Christopher P. 
Published: November 2006

OBJECTIVE. The objective of this study was to determine the frequency and types of pediatric medication errors attributable to design features of a computerized order entry system.
METHODS. A total of 352 randomly selected, inpatient, pediatric admissions were reviewed retrospectively for identification of medication errors, 3 to 12 months after implementation of computerized order entry. Errors were identified and classified by using an established, comprehensive, active surveillance method. Errors attributable to the computer system were classified according to type.
RESULTS. Among 6916 medication orders in 1930 patient-days, there were 104 pediatric medication errors, of which 71 were serious (37 serious medication errors per 1000 patient-days). Of all pediatric medication errors detected, 19% (7 serious and 13 with little potential for harm) were computer related. The rate of computer-related pediatric errors was 10 errors per 1000 patient-days, and the rate of serious computer-related pediatric errors was 3.6 errors per 1000 patient-days. The following 4 types of computer-related errors were identified: duplicate medication orders (same medication ordered twice in different concentrations of syrup, to work around computer constraints; 2 errors), drop-down menu selection errors (wrong selection from a drop-down box; 9 errors), keypad entry error (5 typed instead of 50; 1 error), and order set errors (orders selected from a pediatric order set that were not appropriate for the patient; 8 errors). In addition, 4 preventable adverse drug events in drug ordering occurred that were not considered computer-related but were not prevented by the computerized physician order entry system.
CONCLUSIONS. Serious pediatric computer-related errors are uncommon (3.6 errors per 1000 patient-days), but computer systems can introduce some new pediatric medication errors that are not typically seen in a paper ordering system.
Vitamin D Status in Children and Young Adults With Inflammatory Bowel Disease
Authors: Pappa Helen M. , Gordon Catherine M. , Saslowsky Tracee M. , Zholudev Anna , Horr Brian , Shih Mei-Chiung , Grand Richard J. 
Published: November 2006

OBJECTIVES. Previous studies of vitamin D status in pediatric patients with inflammatory bowel disease have revealed conflicting results. We sought to report (1) the prevalence of vitamin D deficiency (serum 25-hydroxy-vitamin D concentration ≤15 ng/mL) in a large population with inflammatory bowel disease, (2) factors predisposing to this problem, and (3) its relationship to bone health and serum parathyroid hormone concentration.
PATIENTS AND METHODS. A total of 130 patients (8–22 years of age) with inflammatory bowel disease, 94 with Crohn disease and 36 with ulcerative colitis, had serum 25-hydroxy-vitamin D, intact parathyroid hormone, and lumbar spine bone mineral density (using dual-energy x-ray absorptiometry) measured at Children’s Hospital Boston.
RESULTS. The prevalence of vitamin D deficiency was 34.6%. Mean serum 25-hydroxy-vitamin D concentration was similar in patients with Crohn disease and ulcerative colitis, 52.6% lower among patients with dark skin complexion, 33.4% lower during the winter months (December 22 to March 21), and 31.5% higher among patients who were taking vitamin D supplements. Serum 25-hydroxy-vitamin D concentration was positively correlated with weight and BMI z score, disease duration, and serum albumin concentration and negatively correlated with erythrocyte sedimentation rate. Patients with Crohn disease and upper gastrointestinal tract involvement were more likely to be vitamin D deficient than those without it. Serum 25-hydroxy-vitamin concentration was not associated with lumbar spine bone mineral density z score or serum parathyroid hormone concentration.
CONCLUSIONS. Vitamin D deficiency is highly prevalent among pediatric patients with inflammatory bowel disease. Factors predisposing to the problem include having a dark-skin complexion, winter season, lack of vitamin D supplementation, early stage of disease, more severe disease, and upper gastrointestinal tract involvement in patients with Crohn disease. The long-term significance of hypovitaminosis D for this population is unknown at present and merits additional study.
Impact of Umbilical Cord Cleansing With 4.0% Chlorhexidine on Time to Cord Separation Among Newborns in Southern Nepal: A Cluster-Randomized, Community-Based Trial
Authors: Mullany Luke C. , Darmstadt Gary L. , Khatry Subarna K. , LeClerq Steven C. , Katz Joanne , Tielsch James M. 
Published: November 2006

OBJECTIVE. Within a community-based, cluster-randomized study of the effects of 4.0% chlorhexidine on omphalitis and mortality risk, we aimed to describe the distribution of times to separation and the impact of topical chlorhexidine treatment on cord-separation times.
METHODS. Between November 2002 and March 2005, 15123 infants were assigned randomly within communities in southern Nepal to receive 1 of the following 3 cord-care regimens: cleansing with 4.0% chlorhexidine, cleansing with soap and water, or dry cord care. In intervention clusters, field workers cleansed the cord in the home on days 1, 2, 3, 4, 6, 8, and 10 after birth. Newborns were monitored throughout the newborn period for signs of omphalitis, and the time to cord separation was noted. Separation times were compared across treatment groups. Cord infection risk and a range of infant and household characteristics were assessed for their relationships to separation time.
RESULTS. The mean separation time was shorter in dry cord care (4.24 days) and soap/water (4.25 days) clusters than in chlorhexidine clusters (5.32 days; mean difference: 1.08 days). Cords of infants who received chlorhexidine were 3.6 times more likely to separate after 7 days. Separation time was not associated with omphalitis. Home-delivered topical antiseptics, facility-based birth, and birth attendant hand-washing were associated with greater likelihoods of cord separation after 7 days of age.
CONCLUSIONS. In this setting, the umbilical cord separated more rapidly than observed in hospital-based studies, and the impact of chlorhexidine cleansing on separation times was negligible. Increased cord-separation time attributable to topical chlorhexidine treatment should not be considered a factor in decision-making in settings where the baseline risk of omphalitis is high and chlorhexidine might reduce infection and mortality risks significantly.
Childhood Depressive Symptoms and Early Onset of Alcohol Use
Authors: Wu Ping , Bird Hector R. , Liu Xinhua , Fan Bin , Fuller Cordelia , Shen Sa , Duarte Cristiane S. , Canino Glorisa J. 
Published: November 2006

OBJECTIVES. Few studies have assessed the relationship between depressive symptoms and early onset of alcohol use in children and early adolescents. We aimed to determine whether depressive symptoms in children are associated with subsequent initiation of alcohol use and, if so, whether this association is merely a result of demographic, parental, and/or individual risk factors shared by depression and alcohol use or independent of these shared risk factors.
METHODS. Analyses were based on a subsample of 10- to 13-year-old children (N = 1119) from the Boricua Youth Study, a longitudinal study of psychopathology among Puerto Rican children and early adolescents. Children in the study were assessed over 3 waves between 2000 and 2004. In-person structured interviews were conducted with both parents and children.
RESULTS. Depressive symptoms and alcohol use shared some significant risk and protective factors, such as parental psychopathology, parenting, child exposure to violence, and antisocial behaviors. After controlling for these factors, the association between depressive symptoms and alcohol use was reduced, but childhood depressive symptoms were still positively associated with subsequent alcohol use initiation. Children with medium or high levels of depressive symptoms were more than twice as likely to use alcohol as those with &lt;2 depressive symptoms.
CONCLUSIONS. The finding of the current study that early life depressive symptoms may lead to earlier onset of alcohol use indicates the importance of identifying and treating depressive symptoms in preadolescent children. It also demonstrates the importance of examining shared risk and protective factors for understanding the relationship between depressive symptoms and alcohol use.
Acute Pediatric Rhabdomyolysis: Causes and Rates of Renal Failure
Authors: Mannix Rebekah , Tan Mei Lin , Wright Robert , Baskin Marc 
Published: November 2006

OBJECTIVES. The goals were to (1) compare the causes, clinical presentation, and prevalence of acute renal failure in pediatric rhabdomyolysis with the published data for adults; (2) determine predictors of acute renal failure in pediatric patients with rhabdomyolysis; and (3) explore the relationship of acute renal failure with treatment modalities such as fluid and bicarbonate administration.
METHODS. We performed a retrospective chart review to identify patients with creatinine kinase levels of &gt;1000 IU/L who were treated in the emergency department of a tertiary pediatric hospital between 1993 and 2003, and we constructed regression models.
RESULTS. Two hundred ten patients were studied. One hundred ninety-one patients met study eligibility (128 male and 63 female), with a median age of 11 years. The most common documented symptoms were muscle pain (45%), fever (40%), and symptoms of viral infection (39%). The most common causes of pediatric rhabdomyolysis were viral myositis (38%), trauma (26%), and connective tissue disease (5%). Six of 37 patients with creatinine kinase levels of ≥6000 IU/L had previously undiagnosed dermatomyositis or hereditary metabolic disease, compared with 10 of 154 patients with creatinine kinase levels of 1000 to 5999 IU/L. Nine of 191 patients developed acute renal failure. None of 99 patients with initial urinary heme dipstick results of &lt;2+ developed acute renal failure, compared with 9 of 44 patients with urinary heme dipstick results of ≥2+. Higher initial creatinine kinase levels and higher fluid administration rates were associated with higher maximal creatinine levels.
CONCLUSIONS. The cause of acute pediatric rhabdomyolysis is different from that of adult rhabdomyolysis. The risk of acute renal failure in children is much less than the risk reported for adults.
Social Circumstances and Education: Life Course Origins of Social Inequalities in Metabolic Risk in a Prospective National Birth Cohort
Authors: Langenberg Claudia , Kuh Diana , Wadsworth Michael E.J. , Brunner Eric , Hardy Rebecca 
Published: November 2006

Objectives. We investigated the relative importance of education and childhood and adult social class in the risk of metabolic syndrome. Methods. We conducted a prospective birth cohort study of 1311 men and 1318 women aged 53 years in 1999, when metabolic syndrome components were measured. Logistic regression analyses were used to calculate relative index of inequality estimates. Results. Relative to men and women at the highest education levels, men (odds ratio [OR]=2.0; 95% confidence interval [CI]=1.2, 3.2) and women (OR=2.7; 95% CI=1.5, 4.6) with the least education were at twice the risk or more of having the metabolic syndrome. Adjustment for childhood and adult social class strengthened this result among men and weakened it among women. Childhood social class was independently associated with the metabolic syndrome in women (OR=2.0; 95% CI=1.1, 3.6) but not in men (OR=1.1; 95% CI= 0.7, 1.8). Associations between adult social class and the metabolic syndrome or its components were largely accounted for by childhood socioeconomic measures. Conclusions. Educational differences should be considered in the design of interventions aimed at reducing the burden of the metabolic syndrome in socially disadvantaged groups.
Reducing Racial/Ethnic Disparities in Female Breast Cancer: Screening Rates and Stage at Diagnosis
Authors: Sassi Franco , Luft Harold S. , Guadagnoli Edward 
Published: November 2006

Objectives. We assessed whether population rates of mammography screening, and their changes over time, were associated with improvements in breast cancer stage at diagnosis and whether the strength of this association varied by race/ethnicity.Methods. We analyzed state cancer registry data linked to socioeconomic characteristics of patients’ areas of residence for 1990–1998 time trends in the likelihood of early stage diagnosis. We appended each cancer registry record with matching subgroup estimates of self-reported mammography screening.Results. Trends in screening and stage at diagnosis were consistent within groups, but African American women had a significantly lower proportion of early stage cancers despite an advantage in screening. Population screening rates were significantly associated with early diagnosis, with a weaker association in African American women than White women (odds ratio [OR] = 1.70; P<.0001 vs OR=2.02; P<.0001, respectively).Conclusions. Improvements in screening rates during the 1990s across racial/ethnic groups appear to have contributed significantly to earlier diagnosis within each group, but a smaller effect in African American women should raise concerns. A key health policy challenge is to ensure that screening effectively translates into earlier diagnosis.