tbuckley/cabot-search huggingface dataset:
Systematic Review: Surveillance for Breast Cancer in Women Treated With Chest Radiation for Childhood, Adolescent, or Young Adult Cancer
Authors: Tara O. Henderson, Alison Amsterdam, Smita Bhatia, Melissa M. Hudson, Anna T. Meadows, Joseph P. Neglia, Lisa R. Diller, Louis S. Constine, Robert A. Smith, Martin C. Mahoney, Elizabeth A. Morris, Leslie L. Montgomery, Wendy Landier, Stephanie M. Smith, Leslie L. Robison, Kevin C. Oeffinger
Journal: Annals of Internal Medicine (2010)

Background: Women treated with therapeutic chest radiation may develop breast cancer. Purpose: To summarize breast cancer risk and breast cancer surveillance in women after chest radiation for pediatric or young adult cancer. Data Sources: Studies from MEDLINE, EMBASE, the Cochrane Library, and CINAHL (1966 to December 2008). Study Selection: Articles were selected to answer any of 3 questions: What is the incidence and excess risk for breast cancer in women after chest radiation for pediatric or young adult cancer? For these women, are the clinical characteristics of breast cancer and the outcomes after therapy different from those of women with sporadic breast cancer in the general population? What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation? Data Extraction: Three investigators independently extracted data and assessed study quality. Data Synthesis: Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by age 40 to 45 years ranged from 13% to 20%. Risk for breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of breast cancer in these women and the outcomes after diagnosis are similar to those of women in the general population; mammography can detect breast cancer, although sensitivity is limited. Limitation: The quality of evidence for key questions 2 and 3 is limited by substantial study heterogeneity, variation in study design, and small sample size. Conclusion: Women treated with chest radiation have a substantially elevated risk for breast cancer at a young age, which does not seem to plateau. In this high-risk population, there seems to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance. Primary Funding Source: National Cancer Institute.
Increased Frequency of Aberrations in the p53/MDM2/p14<i>ARF</i> Pathway in Neuroblastoma Cell Lines Established at Relapse
Authors: Jane Carr, Emma Bell, Andrew D.J. Pearson, Ursula R. Kees, Helen Beris, John Lunec, Deborah A. Tweddle
Journal: Cancer Research (2006)

p53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed neuroblastoma and can contribute to chemoresistance. Our aim was to determine the frequency of p53 mutations, p14(ARF) methylation, or deletion and MDM2 amplification in 23 neuroblastoma cell lines (6 derived at diagnosis and 17 derived at relapse). One cell line was p53 mutant (BE2c) and two cell lines were deleted for p14(ARF) (LAN-6 and SHEP). Two cell lines were methylated for p14(ARF) (GIMEN and PER-108), one of which had low levels of p14(ARF) mRNA expression which increased following demethylation with 5-aza-2/deoxycytidine treatment (GIMEN), and four cell lines were confirmed to be MDM2-amplified. All these cell lines were derived from neuroblastomas at relapse. Inactivation of the p53 pathway was observed in 9 out of 17 neuroblastoma cell lines (53%) established at relapse and in none of the cell lines established from pretreatment tumors. If these data are confirmed in neuroblastoma tumors, this suggests that p53-independent therapy and reactivation of inactive p53 approaches would be useful in the management of relapsed neuroblastoma.
Classification analyses of pediatric concussion assessment battery
Authors: Gerard Gioia, Peter Isquith, Christopher Vaughan
Journal: British Journal of Sports Medicine (2013)

Objective Demonstrate classification statistics (OR, Likelihood Ratios) of a pediatric multi-component battery of neurocognitive tests, child and parent symptom report to identify the presence or absence of concussion. Design Prospective cohort design. Setting Outpatient clinic, teaching hospital. Participants Two groups of children, ages 5–7 years (n=22 per group) and ages 8–12 years (n=67 per group) (≤7 days post-concussion) were compared to gender/age-matched groups of non-injured children. Interventions Predictor variables: Response Speed Composite, Child and Parent Post-Concussion Symptom Inventory (PCSI) symptom scores. Main Outcome Measurements Group membership—concussion, control. Results MANOVAs revealed significant group differences for the Response Speed Composite, Child and Parent PCSI symptom scores for both age groups. Discriminant function analyses conducted on the Child and Parent PCSI scores and Neurocognitive Composite scores independently and in combination indicate parent and child PCSI symptoms and Response Speed demonstrate adequate classification independently; in combination offered greatest rates. For the 5–7 year age group, 73% were correctly classified by the three combined scores (Positive Likelihood Ratio=3.5, Negative Likelihood Ratio=0.58, OR=6.0, 80% Area Under Curve (AUC)). 84% of 8–12 age group were identified correctly by the three combined scores (LR+=47.0, LR−=.30, OR=155, 94% AUC). Relative differences between scores will be demonstrated. Conclusion The multi-component pediatric battery demonstrates appropriate capability to classify children referred for a suspected concussion. Increased parent and child PCSI symptom ratings and decreased neurocognitive performance (Response Speed) increases diagnostic accuracy, assisting the clinician in their clinical decision-making. Competing interests Drs Gioia, Isquith and Vaughan are co-authors of Pediatric ImPACT battery.
Food allergy in irritable bowel syndrome: new facts and old fallacies
Authors: E Isolauri
Journal: Gut (2004)

The notion of food allergy in irritable bowel syndrome (IBS) is not new. However, recent evidence suggests significant reduction in IBS symptom severity in patients on elimination diets, provided that dietary elimination is based on foods against which the individual had raised IgG antibodies. These findings should encourage studies dissecting the mechanisms responsible for IgG production against dietary antigens and their putative role in IBS
Novel Regulators of Kidney Development from the Tips of the Ureteric Bud
Authors: Kai M. Schmidt-Ott, Jun Yang, Xia Chen, Howard Wang, Neal Paragas, Kiyoshi Mori, Jau-Yi Li, Benson Lu, Frank Costantini, Mario Schiffer, Erwin Bottinger, Jonathan Barasch
Journal: Journal of the American Society of Nephrology (2005)

<h3>OBJECTIVE:</h3> To investigate the knowledge, attitude, and practice of health care professionals on the early detection of breast cancer. <h3>METHODS:</h3> A cross-sectional study was conducted in Jeddah and Abha regions of Saudi Arabia from May to November 2009. A detailed questionnaire was distributed to 500 doctors from different hospitals. The questionnaire contained items on the practice of clinical breast examination and mammogram examination, and the doctor9s perception of their roles in education. <h3>RESULTS:</h3> The results of 337 questionnaires analyzed indicated that most health care professionals do not practice clinical breast examination and mammography, and the perception of their roles in education is not as expected. <h3>CONCLUSION:</h3> Health care providers are one of the main barriers in improving early detection of breast cancer in Saudi Arabia. There is a need to increase awareness among health care providers of their role in the fight against breast cancer through focused education and training programs.
Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.
Authors: D de Jong, B M Voetdijk, G J Van Ommen, J C Kluin-Nelemans, G C Beverstock, P M Kluin
Journal: The Journal of Experimental Medicine (1989)

Although follicle center cell (FCC) lymphomas represent mature B cells, a considerable percentage do not have detectable Ig production. We have used Southern blotting and the polymerase chain reaction (PCR) to study the involvement of translocations t(14;18) and t(8;14) in causing defective Ig production in 16 Ig- FCC-derived lymphomas and three Ig- B cell acute lymphoblastic leukemias. In 6 of 19 cases, a t(14;18) was present with the other allele either deleted or in germline. In two cases a t(14;18) and a t(8;14) affected both Ig alleles, as confirmed by karyotyping. In two other cases, rearrangement of both bcl-2 on chromosome 18 and c-myc on chromosome 8 were found as well. Although cytogenetic proof was not available, the latter was probably involved in t(8;14). Restriction map analysis of one more case showed rearrangement on the pseudo-JH3 gene on one allele and t(14;18) on the other. Thus, in 11 of 19 cases, defective Ig H chain production could be explained by the inactivation of both Ig H chain genes due to translocation of one allele, in combination with deletions or defective rearrangements of the other allele. In contrast, in 28 of 30 Ig+ lymphomas, one functional Ig H chain allele was found, either in, or not in, combination with t(14;18). In two cases a single rearranged Ig H chain allele was found in combination with rearrangement of bcl-2. No comigration of the single Ig rearrangement with bcl-2, however, was found both by Southern blotting and PCR, suggesting a variant bcl-2 translocation, which leaves the Ig H chain allele functionally intact.
Eptifibatide and 7E3, but Not Tirofiban, Inhibit α <sub>v</sub> β <sub>3</sub> Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin
Authors: Manjiri Lele, Mansoor Sajid, Nadeem Wajih, George A. Stouffer
Journal: Circulation (2001)

Our objective was to determine whether abciximab, eptifibatide, or tirofiban inhibited ligand binding to alpha(v)beta(3) integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds alpha(IIb)beta(3) on platelets and alpha(v)beta(3) on HUVECs with similar affinity, whereas eptifibatide and tirofiban are thought to be highly specific for alpha(IIb)beta(3). The conclusion that eptifibatide does not bind vascular alpha(v)beta(3) integrins may be premature, however, because recent studies have demonstrated that the affinity of alpha(v)beta(3) for various ligands, including antagonists, is subject to modulation.Abciximab and 7E3, the anti-beta(3) integrin monoclonal antibody from which abciximab was derived, bound alpha(v)beta(3) on HASMCs in a specific and saturable manner and with an affinity similar to binding to alpha(IIb)beta(3) on platelets. 7E3 and eptifibatide inhibited alpha(v)beta(3)-mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on alpha(v)beta(5)- or beta(1)-mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of eptifibatide was similar in magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited alpha(v)beta(3)-mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, eptifibatide inhibited alpha(v)beta(3)-mediated responses to soluble TSP by HASMCs and beta(3) integrin-expressing HEK cells.Eptifibatide and 7E3, but not tirofiban, specifically inhibit alpha(v)beta(3)-mediated binding of human smooth muscle and endothelial cells.
Plasma microRNAs: a potential biomarker for colorectal cancer?
Authors: A. J Schetter, C. C Harris
Journal: Gut (2009)

There is a need to improve early detection screening methods for colorectal cancer (CRC). If detected early, CRC is highly curable. Colonoscopies are a reliable and accurate screening tool but their high cost and invasiveness lead to reduced screening rates. On the other hand, faecal occult blood tests (FOBTs) are less invasive, less expensive, have even been shown to reduce deaths caused by CRC;1 but the limited sensitivity and specificity of FOBT make it a less than ideal screening method for detecting CRC. Many researchers are trying to identify non-invasive screening methodologies, such as blood tests or faecal DNA tests,2 to improve early detection of CRC to reduce the health burden of this disease. Previous work investigated measuring circulating, tumour-associated DNA or mRNA as screens for various cancers with some success.3 In this issue of Gut , Ng et al 4 (see page 1375) report their results of a study on the expression of levels of circulating microRNAs in plasma as a potential biomarker for CRC.

MicroRNAs are small, non-coding RNAs that regulate the translation of specific protein coding genes. Since their discovery in 1993, altered expression of microRNAs has been connected with several diseases, including cancer.5 Altered expression …
CLASSIFICATION OF THYMUS-DERIVED AND MARROW-DERIVED LYMPHOCYTES BY DEMONSTRATION OF THEIR ANTIGEN-BINDING CHARACTERISTICS
Authors: J. S. Haskill, B. E. Elliott, R. Kerbel, M. A. Axelrad, D. Eidinger
Journal: The Journal of Experimental Medicine (1972)

Antigen-binding cells of T and B origin can readily be determined by quantitating the number of sheep erythrocytes per rosette after glutaraldehyde fixation. The T1 and T2 populations have low antigen-binding properties and are very unstable without fixation. The B1 and B2 populations are stable and correlate with precursor and secretory cells. Fixation of rosettes permits a sensitive test for studying differentiation of T and B cells.
Determination of plasma soluble fibrin using a new ELISA method in patients with disseminated intravascular coagulation
Authors: Kenji Okajima, Mitsuhiro Uchiba, Kazunori Murakami, Hiroaki Okabe, Kiyoshi Takatsuki
Journal: American Journal of Hematology (1996)

We measured plasma levels of soluble fibrin (SF) in 98 patients suspected of having disseminated intravascular coagulation (DIC) using a newly developed enzyme-linked immunosorbent assay (ELISA) and investigated the correlations between SF determinations and measurements of other hemostatic molecular markers to determine the diagnostic usefulness of determinations of SF. Patients were classified into four groups according to their clinical and laboratory findings: overt DIC (n = 33), subclinical DIC (n = 23), hypercoagulability (n = 22), and non-DIC (n = 20). SF levels were significantly higher in patients with overt DIC compared with the other three groups and were significantly higher in the subclinical DIC and hypercoagulability groups compared with the non-DIC patients. SF levels increased significantly with each increase in the clinical stage. Although levels of thrombin-antithrombin III complex (TAT), prothrombin fragment 1 + 2 (PF1+2), cross-linked fibrin degradation products (XDP), and plasmin-antiplasmin complex (PAP) were significantly increased in patients with overt DIC compared with non-DIC patients, the values of these hemostatic molecular markers did not consistently show an increase in association with advances in the disease stage. Plasma levels of SF in patients with overt DIC showed a positive correlation with levels of TAT, XDP, and FDP(E), but not with PF1+2 and PAP. Analysis of receiver-operating characteristic curves showed that the sensitivity and specificity of SF were similar to those of XDP for diagnosis of DIC. The sensitivity and specificity of SF for diagnosis of overt DIC were both above 90% when the cut-off value was set at 65 μg/ml. Plasma levels of SF were also increased in patients with extravascular fibrin formation without DIC. Our findings suggest that measurement of plasma levels of SF by this ELISA method is useful for the diagnosis of DIC and the evaluation of the patient's clinical status. © 1996 Wiley-Liss, Inc.
A sensitive and specific phenotypic assay for detection of metallo-β-lactamases and KPC in Klebsiella pneumoniae with the use of meropenem disks supplemented with aminophenylboronic acid, dipicolinic acid and cloxacillin
Authors: C.G. Giske, L. Gezelius, Ø. Samuelsen, M. Warner, A. Sundsfjord, N. Woodford
Journal: Clinical Microbiology and Infection (2010)
Osteomyelitis of the Pubis
Authors: Ramon del Busto
Journal: JAMA (1982)

Seven cases of osteomyelitis of the pubis are reported. Predisposing factors leading to osteomyelitis included parenteral drug abuse in six patients and pelvic surgery in one patient. The average duration of symptoms before diagnosis was three weeks. Needle aspiration of the symphysis pubis was performed in five patients, and culture results were positive in three of them. Two patients with negative cultures of needle aspirates had positive cultures from open biopsy specimens of the symphysis pubis. Blood cultures were done in all patients, and results were positive in two of them. Pseudomonas aeruginosa was the responsible pathogen in five patients, Escherichia coli in one, and Staphylococcus aureus in one. Most patients required several weeks of antibiotic therapy. None required surgical debridement.
Relationship between Hepatitis C and Chronic Kidney Disease
Authors: Judith I. Tsui, Eric Vittinghoff, Michael G. Shlipak, Ann M. O’Hare
Journal: Journal of the American Society of Nephrology (2006)

Previous research supports an association between hepatitis C virus (HCV) infection and glomerulonephritis. However, little is known about the association between HCV and chronic kidney disease. The cross-sectional association between prevalent hepatitis C seropositivity and albuminuria and estimated GFR (eGFR), respectively, was examined among 15,029 participants in the Third National Health and Nutrition Examination Survey (NHANES III). In the multivariate analysis, we noted an age-dependent association between HCV seropositivity and albuminuria (adjusted odds ratios and 95% confidence intervals 0.83, 0.39 to 1.75 for ages 20 to 39; 1.84, 1.00 to 3.37 for ages 40 to 59; 2.47, 1.27 to 4.80 for ≥60 yr of age). There was no significant association observed for hepatitis C seropositivity and low eGFR (<60 ml/min per 1.73 m2; adjusted odds ratios and 95% confidence interval for all ages 0.89, 0.49 to 1.62). Among a representative sample of the US population, hepatitis C is independently associated with albuminuria among adults over the age of 40; however, it does not seem to be significantly associated with a low eGFR in this population-based cross-sectional analysis.
Loss of Tumor Suppressor p53 Decreases PTEN Expression and Enhances Signaling Pathways Leading to Activation of Activator Protein 1 and Nuclear Factor κB Induced by UV Radiation
Authors: Jian Wang, Weiming Ouyang, Jingxia Li, Lixin Wei, Qian Ma, Zhuo Zhang, Qiangsong Tong, Jie He, Chuanshu Huang
Journal: Cancer Research (2005)

Abstract Transcription factor p53 and phosphatase PTEN are two tumor suppressors that play essential roles in suppression of carcinogenesis. However, the mechanisms by which p53 mediates anticancer activity and the relationship between p53 and PTEN are not well understood. In the present study, we found that pretreatment of mouse epidermal Cl41 cells with pifithrin-α, an inhibitor for p53-dependent transcriptional activation, resulted in a marked increase in UV-induced activation of activator protein 1 (AP-1) and nuclear factor κB (NF-κB). Consistent with activation of AP-1 and NF-κB, pifithrin-α was also able to enhance the UV-induced phosphorylation of c-Jun-NH2-kinases (JNK) and p38 kinase, whereas it did not show any effect on phosphorylation of extracellular signal-regulated kinases. Furthermore, the UV-induced signal activation, including phosphorylation of JNK, p38 kinase, Akt, and p70S6K, was significantly enhanced in p53-deficient cells (p53−/−), which can be reversed by p53 reconstitution. In addition, knockdown of p53 expression by its small interfering RNA also caused the elevation of AP-1 activation and Akt phosphorylation induced by UV radiation. These results show that p53 has a suppressive activity on the cell signaling pathways leading to activation of AP-1 and NF-κB in cell response to UV radiation. More importantly, deficiency of p53 expression resulted in a decrease in PTEN protein expression, suggesting that p53 plays a critical role in the regulation of PTEN expression. In addition, overexpression of wild-type PTEN resulted in inhibition of UV-induced AP-1 activity. Because PTEN is a well-known phosphatase involved in the regulation of phosphatidylinositol 3-kinase (PI-3K)/Akt signaling pathway, taken together with the evidence that PI-3K/Akt plays an important role in the activation of AP-1 and NF-κB during tumor development, we anticipate that inhibition of AP-1 and NF-κB by tumor suppressor p53 seems to be mediated via PTEN, which may be a novel mechanism involved in anticancer activity of p53 protein.
Choice of Starting Dose for Molecularly Targeted Agents Evaluated in First-in-Human Phase I Cancer Clinical Trials
Authors: Christophe Le Tourneau, Anastasios Stathis, Laura Vidal, Malcolm J. Moore, Lillian L. Siu
Journal: Journal of Clinical Oncology (2010)

One tenth of the lethal dose to 10% of mice is one of the conventional parameters used to derive a safe starting dose in phase I trials of cytotoxic agents. There is no consensus on which preclinical models and parameters should define the starting dose for molecularly targeted agents.Reports of 81 first-in-human phase I trials evaluating 60 different molecularly targeted agents administered as monotherapy were reviewed. The maximum-tolerated dose (MTD) was defined as the highest safe dose administered to patients, whereas the maximum-administered dose (MAD) was recorded if the MTD was not reached.Fifty-seven of the 81 trials specified the animal model used to determine the starting dose, with 29 (51%) of 57 based on rodent data and 28 (49%) of 57 based on non-rodent data. A wide range of toxicologic parameters was used to select the starting dose. The starting dose exceeded the human MTD in three (3.7%) of 81 trials, and in all three trials, nonhematologic toxicity was dose limiting. The median number of dose levels to reach MTD or MAD from starting dose was five (range, one to 14 dose levels), and the median ratio of MTD or MAD to starting dose was 12 (range, < 1 to 300). Hypothetical doubling of the starting dose appeared to be safe, whereas tripling of the starting dose was unsafe.The derivation of starting dose for first-in-human phase I trials of molecularly targeted agents in patients with cancer is safe but is based on diverse practices using a variety of preclinical toxicologic parameters.