tbuckley/cabot-search huggingface dataset:
Adjuvant 5-Fluorouracil and Leucovorin With or Without Interferon Alfa-2a in Colon Carcinoma: National Surgical Adjuvant Breast and Bowel Project Protocol C-05
Authors: N. Wolmark, R. Smith, B. Fisher, J. Bryant, D. Hyams, J. Atkins, N. Dimitrov, R. Oishi, D. Prager, L. Fehrenbacher, E. Romond, L. Colangelo, J. Grem, C. Allegra
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. Methods: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. Results: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). Conclusion: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.
Longitudinal study of childhood wheezy bronchitis and asthma: outcome at age 42
Authors: E. Horak
Journal: BMJ (2003)

the timing of the data collection, our information could not be biased by the women's knowledge about the outcome of pregnancy.Potential misclassification is likely to be non-differential, and our results may thus underestimate the true association between coffee drinking and stillbirth.Due to a higher intake of coffee and a faster metabolism among smokers 15 16 we hypothesised that the fetotoxic effect of caffeine could depend on smoking habits during pregnancy.However, the risk of stillbirth associated with coffee was similar in smokers and non-smokers.There did not seem to be one single cause that could explain the increased risk of stillbirth among women with a high intake of coffee (see bmj.com).Information on coffee intake during pregnancy was missing in a quarter of the population.Women with missing information had a different risk profile than women with valid information.However, we have no reason to believe that the association between coffee and stillbirth among women with non-valid information would be different from the one we found.
Asbestosis: assessment by bronchoalveolar lavage and measurement of pulmonary epithelial permeability.
Authors: A R Gellert, J A Langford, R J Winter, S Uthayakumar, G Sinha, R M Rudd
Journal: Thorax (1985)

Thirty two patients with asbestosis were assessed by means of bronchoalveolar lavage (27 patients) and the half time clearance from lungs to blood (T1/2LB) of an inhaled aerosol of diethylenetriamine pentacetate (DTPA) labelled with technetium 99m (32 patients). T1/2LB was also measured in 20 non-smoking normal individuals and 17 smokers without a history of exposure to asbestos. Thirteen patients (46%) showed an increase in the percentage of neutrophils with or without an increase in the percentage of eosinophils and eight (29%) showed an increased percentage of lymphocytes. The number of neutrophils plus eosinophils expressed as a percentage of the total count was positively correlated with the length of the history of disease (r = 0.53, p less than 0.025) and greater percentages were associated with more severe impairment of lung function. Smokers had lower percentages of lymphocytes than non-smokers (p less than 0.002) and showed increased proportions of neutrophils and eosinophils more often than non-smokers (p less than 0.05). In 18 non-smokers with asbestosis the mean T1/2LB was 33.8 (range 10.0-62.0) minutes, significantly less than 57.2 (30.5-109) minutes in 20 non-smoking normal subjects (p less than 0.002). In non-smokers shorter T1/2LB correlated with a longer time since first exposure to asbestos (r = -0.65, p less than 0.005), longer duration of exposure (r = -0.70, p less than 0.001), and a shorter time since last exposure (r = 0.59, p less than 0.01). Shorter T1/2LB was also associated with increased inflammatory activity as shown by higher bronchoalveolar lavage cell counts (r = -0.53, p less than 0.025) and higher combined percentages of neutrophils, eosinophils, and lymphocytes (r = -0.47, p less than 0.05). The techniques of bronchoalveolar lavage and measurement of inhaled solute clearance may be useful in assessing inflammatory activity in asbestosis.
Mutation of the <b> <i>PIK3CA</i> </b> Gene in Ovarian and Breast Cancer
Authors: Ian G. Campbell, Sarah E. Russell, David Y. H. Choong, Karen G. Montgomery, Marianne L. Ciavarella, Christine S. F. Hooi, Briony E. Cristiano, Richard B. Pearson, Wayne A. Phillips
Journal: Cancer Research (2004)

Abstract Phosphatidylinositol 3′-kinases are lipid kinases with important roles in neoplasia. Recently, a very high frequency of somatic mutations in PIK3CA has been reported among a large series of colorectal cancers. However, the relevance of PIK3CA mutation in other cancer types remains unclear because of the limited number of tumors investigated. We have screened a total of 284 primary human tumors for mutations in all coding exons of PIK3CA using a combination of single stranded conformational polymorphism and denaturing high-performance liquid chromatography analysis. Among 70 primary breast cancers, 40% (28 of 70) harbored mutations in PIK3CA, making it the most common mutation described to date in this cancer type. Mutations were not associated with histologic subtype, estrogen receptor status, grade or presence of tumor in lymph nodes. Among the primary epithelial ovarian cancers only 11 of 167 (6.6%) contain somatic mutations, but there was a clear histologic subtype bias in their distribution. Only 2 of 88 (2.3%) of serous carcinomas had PIK3CA mutations compared with 8 of 40 (20.0%) endometrioid and clear cell cancers, which was highly significant (P = 0.001). In contrast, PIK3CA gene amplification (&amp;gt;7-fold) was common among all histologic subtypes (24.5%) and was inversely associated with the presence of mutations. Overall, PIK3CA mutation or gene amplification was detected in 30.5% of all ovarian cancers and 45% of the endometrioid and clear cell subtypes. Our study is the first direct evidence that PIK3CA is an oncogene in ovarian cancer and greatly extends recent findings in breast cancer.
Contact dermatitis in students practicing sports: incidence of rubber sensitisation
Authors: M T Ventura, M Dagnello, M G Matino, R Di Corato, G Giuliano, A Tursi
Journal: British Journal of Sports Medicine (2001)

Over the last few years, changes in cutaneous homoeostasis resulting from sports activities have been reported. In particular, alterations in sweating mechanisms, the hydrolipid barrier, and surface bacterial flora, together with exposure to atmospheric conditions and the need to use medicaments, detergents, and other topical substances, predispose subjects to allergic contact dermatitis.To evaluate the incidence of allergic contact dermatitis in a group of young people practising sports activities.Patch tests were performed to confirm the diagnosis of irritant or allergic dermatitis; in addition, the radioallergoabsorbent test (RAST) to latex was evaluated in the group studied.Allergic contact dermatitis caused by thiourams (23.3%) and mercaptobenzothiazole (20.9%) was prevalent. Other haptens, such as benzocaine and nickel, which are contained in clothing, equipment, topical medicaments, and creams used for massage, were also allergenic. In two cases, RAST positivity to latex was registered.-The results suggest that close contact with sports equipment may increase the incidence of allergic contact dermatitis. Students practising certain sports may have "professional" allergic contact dermatitis to additives used in the production of rubber.
EFFECT OF REPEATED FREEZING (–185°C.) AND THAWING ON COLON BACILLI, VIRUS III, VACCINE VIRUS, HERPES VIRUS, BACTERIOPHAGE, COMPLEMENT, AND TRYPSIN
Authors: T. M. Rivers
Journal: The Journal of Experimental Medicine (1927)

Colon bacilli, Virus III, vaccine virus, herpes virus, bacteriophage, complement, and trypsin are either killed or inactivated by repeated freezing (–185°C.) and thawing. As might be expected, some of the agents are more resistant than others. Hence it may be concluded that destruction or inactivation of an active agent by repeated freezing (–185°C.) and thawing is not proof that it was possessed of life.
NEONATAL SCREENING FOR CONGENITAL ADRENAL HYPERPLASIA
Authors: E. Cacciari, A. Balsamo, S. Piazzi, S. Salardi, P. Pirazzili, M. Capelli, A. Cassio, F. Bernardi, A. Cicognani, F. Zappulla, M. Paolini
Journal: The Lancet (1982)
Tilarin in combination with astemizole
Authors: Donald A. Bukstein, Robert M. Biondi, Malcolm M. Blumenthal, Robert J. Dockhorn, Warren V. Filley, Jordan Fink, Stanley Goldsteln, David F. Graft, S. Roger Hirsch, Thaddeus H. Joos, Julian Melamed, Michael S. Rowe, Robert G. Townley
Journal: Allergy (1996)

Bukstein D. A., Biondi R. M., Blumenthal M. M., Dockhorn R. J., Filley W I!, Fink J., Goldstein S., Graft D. E, Hirsch S. R., Joos T. H., Melamed J., Rowe M. S., Townley R. G. Tilarin in combination with astemizole. This multicentre double-blind, placebo controlled study had a practical objective, based on the expectation that many patients with seasonal allergic rhinitis will be prescribed oral antihistamine monotherapy by their primary care physician, whereas allergy specialists are more likely to prescribe combination therapy including antiinflammatories. The specific question was, 'Will the addition of nedocromil sodium 1% nasal spray to astemizole tablets improve control of symptoms of seasonal allergic rhinitis induced by ragweed pollen, as compared to astemizole therapy alone?'. Following a one-week baseline, planned to coincide with the start of the local ragweed pollen season, patients (aged 12–64) were randomly assigned to four weeks' double-blind test treatment with either nedocromil sodium 1% nasal spray four times daily (QID)+astemizole (n=146) or placebo nasal spray+astemizole (n=148) or double-dummy (nasal spray+capsules) placebo (n=71). Patient diary cards were kept throughout the five weeks, and clinic visits were made before and after baseline and after one and four weeks' treatment. During the 10-day peak pollen period, the diary card rhinitis symptom summary score (0–1 severity scale) was significantly reduced in patients receiving either astemizole alone (p < 0.001) or the combination therapy (p<0.001) as compared with placebo. Direct comparison of the active treatments further showed that symptoms were signficantly less severe (p < 0.01) with the combined therapy than with astemizole alone, and this despite significantly greater reliance on permitted rescue medications (p < 0.05 for pseudoephedrine usage) in the astemizole group. Clinical assessments of rhinitis made during the peak pollen visit, after the first week of test treatment, were also significantly (p < 0.05-p < 0.01) in favour of combined therapy with nedocromil sodium 1% nasal spray+astemizole rather than astemizole alone, and at the same time this preference was confirmed by physician (p=0.011) and patient (p=0.003) opinions of symptom control. In conclusion, this antiinflammatory+ antihistamine treatment proved superior to antihistamine alone for effective management of allergic rhinitis. The combined therapy worked quickly and was well-tolerated, with no serious adverse events or untoward effects on blood or urine variables.
Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial
Authors: Tihamer Orban, Brian Bundy, Dorothy J Becker, Linda A DiMeglio, Stephen E Gitelman, Robin Goland, Peter A Gottlieb, Carla J Greenbaum, Jennifer B Marks, Roshanak Monzavi, Antoinette Moran, Philip Raskin, Henry Rodriguez, William E Russell, Desmond Schatz, Diane Wherrett, Darrell M Wilson, Jeffrey P Krischer, Jay S Skyler
Journal: The Lancet (2011)
Collateral Flow to the Territory of the Occluded Infarct-Related Artery
Authors: Kanu Chatterjee
Journal: Circulation (2010)

T ime and time again, randomized clinical trials have demonstrated that what is conceptually logical and should be right is not always right.Randomized large clinical trials are often undertaken on the basis of this logical hypothesis.Very often, small clinical trials also show encouraging results. 1,2However, when large randomized clinical trials are performed, they not infrequently reveal rather disappointing and unexpected results.The study by Steg et al, "Impact of Collateral Flow to the Occluded Infarct-Related Artery on Clinical Outcomes in Patients with Recent Myocardial Infarction: A Report From the Randomized Occluded Artery Trial," reported in this issue of Circulation, proves this again.
Differential T Cell Function and Fate in Lymph Node and Nonlymphoid Tissues
Authors: Nicola L. Harris, Victoria Watt, Franca Ronchese, Graham Le Gros
Journal: The Journal of Experimental Medicine (2002)

The functions and fate of antigen-experienced T cells isolated from lymph node or nonlymphoid tissues were analyzed in a system involving adoptive transfer of in vitro-activated T cells into mice. Activated T cells present in the lymph nodes could be stimulated by antigen to divide, produce effector cytokines, and migrate to peripheral tissues. By contrast, activated T cells that had migrated into nonlymphoid tissues (lung and airway) produced substantial effector cytokines upon antigen challenge, but were completely unable to divide or migrate back to the lymph nodes. Therefore, activated T cells can undergo clonal expansion in the lymph node, but are recruited and retained as nondividing cells in nonlymphoid tissues. These distinct regulatory events in lymph node and nonlymphoid tissues reveal simple key mechanisms for both inducing and limiting T cell immunity.
MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.
Authors: N W Toribara, J R Gum, P J Culhane, R E Lagace, J W Hicks, G M Petersen, Y S Kim
Journal: Journal of Clinical Investigation (1991)

MUC-2, the first described intestinal mucin gene, has become important as a prototype for secreted mucins in several organ systems. However, little is known about its protein backbone structure and hence its role in diseases such as colon cancer, ulcerative colitis, and cystic fibrosis, which are known to have mucin abnormalities. Studies in this manuscript show that MUC-2 contains two distinct regions with a high degree of internal homology, but the two regions bear no significant homology to each other. Region 1 consists mostly of 48-bp repeats which are interrupted in places by 21-24-bp segments. Several of these interrupting sequences show similarity to each other, creating larger composite repeat units. Region 1 has no length polymorphisms. Region 2 is composed of 69-bp tandem repeats arranged in an uninterrupted array of up to 115 individual units. Southern analysis of genomic DNA samples using TaqI and HinfI reveals both length and sequence polymorphisms which occur within region 2. The sequence polymorphisms have different ethnic distributions, while the length polymorphisms are due to variable numbers of tandem repeats.
Central sleep apnoea syndrome with upper airway collapse
Authors: JL Pepin, A Pajon, D Veale, G Ferretti, P Levy
Journal: European Respiratory Journal (1993)

We report on an 83 yr old man with hypersomnia and central sleep apnoea (CSA). He had several possible causes for CSA, including a central nervous system lesion, hypocapnia and anatomical narrowing of the airway at the hypopharyngeal level. We postulate that reduced central respiratory drive occurring in conjunction with upper airway narrowing may have led to central apnoeas. These in turn could have facilitated a complete passive hypopharyngeal collapse at the end of each apnoea, as visualized by somnofluoroscopy. The CSA could also have been favoured by respiratory instability due to chronic hypocapnia.
Down-regulation of Na+/H+ Exchanger Regulatory Factor 1 Increases Expression and Function of Multidrug Resistance Protein 4
Authors: Md. Tozammel Hoque, Susan P.C. Cole
Journal: Cancer Research (2008)

Abstract Multidrug resistance protein 4 (MRP4; ABCC4) is a member of the ATP-binding cassette superfamily of membrane transport proteins and confers resistance to nucleoside and nucleotide analogues as well as camptothecin derivatives. MRP4 also mediates the transmembrane transport of several eicosanoids, conjugated estrogens, and cyclic AMP. The subcellular localization of MRP4 depends on the cell type in which it is expressed, but the molecular determinants responsible for trafficking of MRP4 to the plasma membrane are unknown. Here, we describe the interaction of Na+/H+ exchanger regulatory factor 1 (NHERF1) with MRP4 via the last four amino acids (1322ETAL1325) of the transporter. Down-regulation of NHERF1 by small interfering RNA (siRNA) in HeLa cells significantly increased MRP4 levels at the plasma membrane, suggesting that internalization of the transporter was inhibited. Increased plasma membrane MRP4 was accompanied by increased efflux function as reflected by reduced cellular accumulation of the MRP4 substrates 6-mercaptopurine and 9-[2-(phosphonylmethoxy)ethyl]-adenine. Furthermore, enhanced green fluorescent protein-tagged MRP4 was internalized in monensin-treated cells, and this internalization was markedly reduced after NHERF1 down-regulation by siRNA. Together, these data establish NHERF1 as a novel protein-binding partner of MRP4 that plays a significant role in the internalization and drug efflux function of this transporter. [Cancer Res 2008;68(12):4802–9]
Down-regulation of CXCL5 Inhibits Squamous Carcinogenesis
Authors: Hiroshi Miyazaki, Vyomesh Patel, Huixin Wang, Ryan K. Edmunds, J. Silvio Gutkind, W. Andrew Yeudall
Journal: Cancer Research (2006)

Abstract We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we reported transcriptional up-regulation of CXCL5 in metastatic cells. In this study, we provide biological validation of these findings and show that CXCL5 is intimately involved in tumor cell proliferation, migration, and invasion. Cells derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA interference to generate cell lines (shL5) in which CXCL5 expression was greatly reduced, and tested whether this modulated the cell phenotype. shL5 cells showed decreased proliferation compared with cells harboring nontargeting control sequences. In addition, we found that the ability of shL5 cells to migrate and invade in vitro through a basement membrane substitute was greatly impaired compared with control cells. Finally, whereas control cells were highly tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was found to be ablated. Taken together, these data suggest that CXCL5 production contributes to both enhanced proliferation and invasion of squamous cell carcinomas and that targeting of chemokine pathways may represent a potential therapeutic modality for these lesions. (Cancer Res 2006; 66(8):4279-84)
Obesity is associated with hypothalamic injury in rodents and humans
Authors: Joshua P. Thaler, Chun-Xia Yi, Ellen A. Schur, Stephan J. Guyenet, Bang H. Hwang, Marcelo O. Dietrich, Xiaolin Zhao, David A. Sarruf, Vitaly Izgur, Kenneth R. Maravilla, Hong T. Nguyen, Jonathan D. Fischer, Miles E. Matsen, Brent E. Wisse, Gregory J. Morton, Tamas L. Horvath, Denis G. Baskin, Matthias H. Tschöp, Michael W. Schwartz
Journal: Journal of Clinical Investigation (2011)

Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.
An Antibody-Deficiency Syndrome Due to Mutations in the<i>CD19</i>Gene
Authors: Menno C. van Zelm, Ismail Reisli, Mirjam van der Burg, Diana Castaño, Carel J.M. van Noesel, Maarten J.D. van Tol, Cristina Woellner, Bodo Grimbacher, Pablo J. Patiño, Jacques J.M. van Dongen, José L. Franco
Journal: New England Journal of Medicine (2006)

The CD19 protein forms a complex with CD21, CD81, and CD225 in the membrane of mature B cells. Together with the B-cell antigen receptor, this complex signals the B cell to decrease its threshold for activation by the antigen.We evaluated four patients from two unrelated families who had increased susceptibility to infection, hypogammaglobulinemia, and normal numbers of mature B cells in blood. We found a mutation in the CD19 gene in all four patients. The CD19 gene in the patients and their first-degree relatives was sequenced, and flow-cytometric immunophenotyping of B cells, immunohistochemical staining of lymphoid tissues, and DNA and messenger RNA analysis were performed. B-cell responses on the triggering of the B-cell receptor were investigated by in vitro stimulation; the antibody response after vaccination with rabies vaccine was also studied.All four patients had homozygous mutations in the CD19 gene. Levels of CD19 were undetectable in one patient and substantially decreased in the other three. Levels of CD21 were decreased, whereas levels of CD81 and CD225 were normal, in all four patients. The composition of the precursor B-cell compartment in bone marrow and the total numbers of B cells in blood were normal. However, the numbers of CD27+ memory B cells and CD5+ B cells were decreased. Secondary follicles in lymphoid tissues were small to normal in size and had a normal cellular composition. The few B cells that showed molecular signs of switching from one immunoglobulin class to another contained V(H)-C(alpha) and V(H)-C(gamma) transcripts with somatic mutations. The response of the patients' B cells to in vitro stimulation through the B-cell receptor was impaired, and in all four patients, the antibody response to rabies vaccination was poor.Mutation of the CD19 gene causes a type of hypogammaglobulinemia in which the response of mature B cells to antigenic stimulation is defective.