tbuckley/cabot-search huggingface dataset:
Elevated myelin basic protein levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia.
Authors: D H Mahoney, D J Fernbach, D G Glaze, S R Cohen
Journal: Journal of Clinical Oncology (1984)

Cerebrospinal fluid was examined from 70 children with acute lymphoblastic leukemia for evidence of active myelin breakdown based on the release of myelin basic protein (MBP). Fifty-three asymptomatic children were followed from diagnosis with serial MBP determinations. Eight (15.1%) of 53 children had abnormal elevations of MBP, six of eight before receiving presymptomatic central nervous system therapy. Long-term observations are in progress. For comparison, six children with clinical and radiologic findings of leukoencephalopathy had abnormal MBP determinations, whereas no abnormalities were detected in 11 children with meningeal leukemia.
Platinum Antitumor Complexes: 50 Years Since Barnett Rosenberg's Discovery
Authors: Franco M. Muggia, Andrea Bonetti, James D. Hoeschele, Marcel Rozencweig, Stephen B. Howell
Journal: Journal of Clinical Oncology (2015)

Author(s): Muggia, Franco M; Bonetti, Andrea; Hoeschele, James D; Rozencweig, Marcel; Howell, Stephen B
Amyloid Pathology, Cognitive Impairment, and Alzheimer Disease Risk—Reply
Authors: Willemijn J. Jansen, Rik Ossenkoppele, Pieter Jelle Visser
Journal: JAMA (2015)

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Isolation of a Precipitating Glycoprotein Antigen From Cell Cultures Persistently Infected with Bovine Leukemia Virus
Authors: Marshall Phillips, Janice M. Miller, Martin J. van der Maaten
Journal: JNCI Journal of the National Cancer Institute (1978)

A procedure was developed to isolate a glycoprotein with precipitating antigen activity from fluids from fetal lamb kidney cell cultures persistently infected with bovine leukemia virus (BLV). The antigen was precipitated by ammonium sulfate and subjected to affinity chromatography on concanavalin A Sepharose. The glycoprotein was eluted with alpha-methyl-D-mannoside and was further purified by gel filtration over Sephadex G-100. Antigen activity was determined by agar gel immunodiffusion (AGID) reactions with serum from cattle infected with the virus. The major portion of the AGID activity was eluted from the Sephadex G-100 in the 60,000-dalton elution region. In some experiments, identical AGID activity was also found in the 18,000-dalton elution region. The larger protein was discovered to have a molecular weight of 58,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its designation as a glycoprotein was confirmed by carbohydrate-positive staining. The isolated BLV glycoprotein antigen did not contain ovine or bovine proteins as indicated by gel immunodiffusion.
Unbiased estimation of evolutionary distance between nucleotide sequences.
Authors: F Tajima
Journal: Molecular Biology and Evolution (1993)

A new algorithm for estimating the number of nucleotide substitutions per site (i.e., the evolutionary distance) between two nucleotide sequences is presented. This algorithm can be applied to many estimation methods, such as Jukes and Cantor's method, Kimura's transition/transversion method, and Tajima and Nei's method. Unlike ordinary methods, this algorithm is always applicable. Numerical computations and computer simulations indicate that this algorithm gives an almost unbiased estimate of the evolutionary distance, unless the evolutionary distance is very large. This algorithm should be useful especially when we analyze short nucleotide sequences. It can also be applied to amino acid sequences, for estimating the number of amino acid replacements.
Stimulation of IL-8 release in respiratory cell cultures by increasing IL1-β concentrations: Effect of budesonide
Authors: Juan Figueroa, Fernanda Elias, Mariana Callello, Andrea Dugour
Journal: European Respiratory Journal (2013)

Background: in airways of patients with severe asthma it have been described higher levels of IL-1β and IL-8. Previously we described that stimulation with IL1-β induces the release of IL-8 in human bronchial cells (Calu-3) and that this effect diminishes with budesonide (BUD).

Objective: to evaluate the effect of increasing concentrations of IL1-β on the release of IL-8 by Calu 3 cells and to establish the action of BUD in this model.

Materials and Methods: cells were cultured in monolayer and exposed to increasing concentrations of IL1-β (10-150 ng / ml) and H2O2 100 uM. After 4 hours of incubation inflammatory agent was removed and cells were treated with BUD (30 and 120 uM) or placebo for 24 hours. IL-8 release was then quantified.

Results: with higher concentrations of IL1-β the release of IL-8 by Calu3 cells was greatest (10 ng of IL1-β induce 54 ng/ml of IL-8; 50 ng of IL1-β induce 78 ng/ml of IL-8). BUD anti-inflammatory effect was lower in cells stimulated with higher concentrations of IL1-β (IL-8 release decrease 12%) than in cells treated with lower concentrations (IL-8 release decrease 30%).

Conclusions: higher IL1-β concentration increase proinflammatory response of respiratory cells and decreases the effect of BUD. The behavior of this model is consistent with clinical and biological data of patients with severe asthma.
Planning for the Development of Comprehensive Community Alcoholism Services: II. Assessing Community Awareness and Attitudes
Authors: ALLAN BEIGEL, THOMAS R. MCCABE, JOHN S. TAMERIN, MARY J. LOWERY, EDWIN H. CHAPIN, E. JAMES HUNTER
Journal: American Journal of Psychiatry (1974)

The authors believe that in the development of an effective community education and treatment program for alcoholism the following dimensions need to be assessed: 1) attitudes toward alcohol use and abuse; 2) drinking habits; 3) awareness of available services and facilities for the alcoholic; 4) extent of personal drinking problems; and 5) comparative perceptions of alcohol abuse in different ethnic groups. After describing the procedure they devised to make these assessments, they present examples of how the data gathered can be used in the planning of comprehensive community alcoholism services.
Most women with early stage breast cancer are tested for metastases despite advice against it, study finds
Authors: J. Clark
Journal: BMJ (2015)

Eighty six per cent of women with early stage breast cancer underwent imaging to determine whether their cancer had spread, contradicting guidelines advising against such testing, a study published in the journal of the Canadian Medical Association, CMAJ , has found.1 

Guidelines of the American Society of Clinical Oncology, the European School of Oncology, and Cancer Care Ontario recommend against imaging for metastatic cancer in asymptomatic women with stage I or II breast cancer, because the likelihood of metastases was low and the rate of false positive results high.

The study of 26 547 women in Ontario who had been …
Clinical potential of new antiestrogens.
Authors: W J Gradishar, V C Jordan
Journal: Journal of Clinical Oncology (1997)

PURPOSE Based on the data and clinical experience derived from tamoxifen usage, the properties of an ideal antiestrogen is described that could have applications as a breast cancer preventative agent, long-term adjuvant therdpy, or as a treatment for osteoporosis. Each of the new antiestrogens currently being tested is discussed in terms of laboratory development, toxicology, pharmacology, endocrinology, and clinical evaluation. And each new compound is assessed according to the properties of an ideal antiestrogen. METHODS A review of all published reports was facilitated by the use of Medline computer searches. RESULTS Numerous compounds are being evaluated in clinical trials and can be categorized as triphenylethylenes or tamoxifen analogs, pure antiestrogens, and targeted antiestrogens. Several of these compounds may have fewer uterotropic properties and greater effects on maintaining bone density compared with tamoxifen; however, the clinical experience (ie, patient-years of treatment) with any of these compounds is minimal. CONCLUSION Although many of these compounds appear promising, further evaluation will be necessary to determine the role these compounds may serve as preventive agents, adjuvant therapies, treatments for advanced disease, or other medical indications such as osteoporosis.
Drug sensitivity pattern (first line ATT) in DOTS failure & relapse cases (Cat I & Cat II) rntcp, India
Authors: Govind Narayan Srivastava, Manoj Meena, Pavan Yadav, Jitendra Meena, Moosa Hussain
Journal: European Respiratory Journal (2012)

BACKGROUND : Patients with pulmonaryTB require retreatment if they fail or develop relapse following the initial treatment on DOTS(Cat I or II). Early diagnosis of such cases is important to prevent the drug resistant tuberculosis. If diagnosed as MDR TB,it should be treated aggressively, thus treatment can be rationalized and outcomes of relapse & failure cases can be improved by performing DST (drug sensitivity test).   OBJECTIVE : To know the drug sensitivity pattern among DOTS failure & relapse cases by culture of sputum & drug sensitivity.   MATERIAL & METHODS : 60 cases who were smear or culture positive at the end of DOTS treatment were registered (cat I & cat II).42 patients out of 60 had already completed cat I DOTS & 18 patients were of DOTS cat II. Early Morning sputum samples were collected for culture & DST in .Egg based LJ media was used for AFB culture & DST. it was performed by using the proportion method. Results were obtained at the end of 6 th  week post culture. All these patients had clinical as well as radiological deterioration after DOTS therapy completion.Study was conducted in dept.of TB & CHEST DISEASES.IMS.   RESULT: 14 patients out of 42 cases of DOTS CAT I turned out to be multi drug resistant cases(33.33%.)which were resistant to H & R respectively.8 out of 18 cases of DOTS CAT II turned out to be MDR cases(44.44%.).   CONCLUSION: 33% of CAT I failure cases developed MDR TB which is very alarming & the result of present trial supports the performance of early culture & DST in all patients of failure & relapse cases.44%of CAT II patients developed MDR TB which is again discouraging & warrants to search the cause behind such high incidence of drug resistance.
The prognostic significance of immune changes in patients with renal cell carcinoma treated with interferon alfa-2b.
Authors: P A Kosmidis, C N Baxevanis, N Tsavaris, M Papanastasiou, E Anastasopoulos, C Bacoyiannis, N Mylonakis, N Karvounis, D Bafaloukos, A Karabelis
Journal: Journal of Clinical Oncology (1992)

PURPOSE To evaluate the response rate and the immunorestorative properties of subcutaneously administered interferon alfa-2b (IFN-A2b) in patients with advanced renal cell carcinoma (RCC) and to correlate the immune status with the clinical responses. PATIENTS AND METHODS Twenty-six patients with advanced RCC were treated with recombinant IFN-A2b. The dose was increased progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week, and thereafter to 15 x 10(6) IU subcutaneously. RESULTS Four patients (15%) achieved partial responses (PRs), and five patients (19%) had stable disease (S), whereas 17 patients (65%) progressed. In all patients, blood was withdrawn before IFN treatment and monthly thereafter. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (autoMLR) and allogeneic mixed lymphocyte reaction (alloMLR), interleukin-2 (IL-2) production, expression of IL-2 receptors during the alloMLR, and the production of interleukin-1 (IL-1) by peripheral-blood monocytes. Twelve patients were assessable, four patients had a PR, one patient had S, and seven patients had progressive disease. Striking increases were demonstrated in all parameters 1 month after treatment with IFN-A2b in the four patients who responded and the patient with S. Namely, the autoMLR responses showed a mean increase of 250%, the IL-2 production 247%, the expression of IL-2-specific receptors 446%, the alloMLR responses 160%, and the production of IL-1 262%. On the contrary, the nonresponders did not show any change in their overall immune status, and in some, deterioration of the already depressed immunologic functions was observed. CONCLUSIONS Administration of IFN-A2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC who respond to the treatment. This may have prognostic significance, and certainly more patients are required to be studied for definite conclusions.
Disodium Cromoglycate Relieves Symptoms in Symptomatic Young Smokers
Authors: A. G. Leitch, E. M. Lumb, A. B. Kay
Journal: Allergy (1984)

We have undertaken a double blind placebo controlled study of disodium cromoglycate (DSCG) in 32 symptomatic young smokers. These individuals had regular morning cough and sputum with the sensation of wheeze, but were not asthmatics as determined by the usual criteria. No significant changes were observed in sputum or serum eosinophils, IgE, IgG or IgA, or sputum histamine concentrations following the administration, for 3 weeks, of either DSCG (20 mg) or placebo, thrice daily. However DSCG, but not placebo, was associated with significant improvements in the symptoms of cough (P less than 0.01) and wheezing (P less than 0.025). We suggest that these changes may be due to an effect of DSCG on the irritant receptor mediated reflex response to cigarette smoke rather than the involvement of mast cells.
Disease progression in IPF assessed using pulmonary function tests and functional respiratory imaging (FRI) – A pilot study
Authors: Jan De Backer, Wim Vos, Gerald Smaldone, Shaji Skaria, Rany Condos
Journal: European Respiratory Journal (2014)

Rationale   Disease progression in IPF is correlated with reduced lobar volume (iLobe), enlarged airway volume (iVaw) and reduced airway impedence (iRaw).   Methods   5 IPF patients were followed for 6 months to assess changes in airway structure and function. At baseline and after 6m FVC, DLCO and 3He-based FRC/TLC were measured. Also, HRCT-based functional respiratory imaging (FRI) was performed. FRI provides information on iLobe, iVaw and iRaw.   Results   In terms of FVC, 1pt declined (-6%), 1pt improved (+6%) and 3pts remained stable (-1%,0%,1%). The pt that declined in FVC also experienced: DLCO -21%, FRC -12.67%, TLC -7.47%. iVaw stayed constant, iRaw decreased by 6.7%. However when iVaw/iRaw are corrected for lung volume (siVaw = iVaw/iLobe, siRaw = iRaw*iLobe), then siVaw increased by 23.99% and siRaw reduced by 30.90%. A negative but not significant correlation was found between changes in FVC and iVaw (R=-0.6, p=0.28). However, significant correlations were found between changes in FVC and siVaw (R=-1, p=0); changes in iLobe and siVaw (in the upper lobes R=-0.71, p=0.00283); and changes in siVaw and lobar ventilation (R=0.42, p=0.035).   Conclusions   By PFT criteria, IPF only progressed in one patient, but the study suggests that IPF progression is associated with a reduction in iLobe, an increase siVaw and a reduction in siRaw. Further studies need to confirm these initial observations.
Time to adjust to changes in ventilation settings varies significantly between different T-piece resuscitators, self-inflating bags and manometer equipped self-inflating bags
Authors: Julia Hartung, Simone Dold, Marta ThioLluch, Gerd Schmalisch, Arjan B. tePas, Charles Christoph Roehr
Journal: European Respiratory Journal (2013)

Background:  Resuscitation guidelines give no preference over use of self-inflating bags (SIB) or T-piece resuscitators (TPR) for manual neonatal ventilation. We speculated devices would differ significantly regarding time required to adjust to changed ventilation settings.  Methods:  Laboratory study. Time to adjust from baseline PIP (20 and 25 cmH2O) to target PIP (25 and 40 cmH2O), ability to adhere to predefined ventilation settings (PIP, PEEP and RR) and the inter-operator variability were assessed for a SIB without manometer, SIB with manometer (SIBM), and two TPRs.  Results:  Adjustment time was significantly longer with TPRs, compared to SIB and SIBM. The SIBM and TPRs were   Conclusions:  PIP adjustment takes longer with TPRs, compared to SIB/SIBM. TPRs and SIBM allow satisfactory adherence to ventilation parameters. SIBs should only be used with manometer attached.
A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes.
Authors: B D Cheson, D M Jasperse, R Simon, M A Friedman
Journal: Journal of Clinical Oncology (1986)

We reviewed 53 publications reporting 751 patients with hematologic malignancies treated with low doses (5 to 20 mg/m2/d) of cytosine arabinoside (LoDAC). Of 507 patients evaluable for response, complete remission (CR) rates varied from 32% for patients with primary acute non-lymphoblastic leukemia (1 degree ANLL) to 16% for patients with hematologic malignancies secondary to previous chemotherapy or following a myelodysplastic syndrome (MDS) (2 degrees ANLL), and 16% for MDS. Median duration of CR was 9.5 months for 1 degree ANLL, and 10.5 months for both 2 degrees ANLL and MDS. Based on limited available survival data, overall median survival for these groups was 9 months, 3 months, and 15 months, respectively. Only three CRs were reported of 31 evaluable patients treated for a variety of other hematologic malignancies. CR rates for patients with 1 degree ANLL greater than or equal to 50 years old was 56%, compared with 29% less than 50 years old (P = .10). While prior chemotherapy was more common in 1 degree ANLL patients less than 50 years of age (86% v 21%; P less than .001), it did not influence response rates in those greater than 50 years of age, suggesting other biases. Hematologic toxicity was mentioned in only 33 of 53 publications, affecting 254 of 289 patients (88%), with at least 15% treatment-related deaths. LoDAC hypothetically acts as a differentiating agent; however, correlative laboratory studies were rarely performed. Cytogenetic data were available for only 15%, and in vitro studies for 10% of all patients with marked discrepancies in the interpretation of results. LoDAC is clearly cytotoxic for both malignant and normal hematopoietic cells. While large numbers of patients have been reported, the lack of well-designed clinical trials prohibits definitive conclusions as to its role as a differentiating agent. Future LoDAC studies should determine optimal dose and schedule, with clinical laboratory correlates to assess differentiation. Trials in ANLL comparing LoDAC with conventional chemotherapy, and in MDS with supportive care alone, may help identify the role of LoDAC. Until appropriate indications can be identified, LoDAC should not be routinely used in clinical practice.
Wnt drives stem cell-mediated repair response after hepatic injury
Authors: Kari N. Nejak-Bowen, Satdarshan P.S. Monga
Journal: Hepatology (2013)

Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, et al . In vitro expansion of single Lgr5 + liver stem cells induced by Wnt-driven regeneration. Nature 2013;494:247-250. (Reprinted with permission.) Abstract The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A three-dimensional culture system allows long-term clonal expansion of single Lgr5+ stem cells into transplantable organoids (budding cysts) that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist RSPO1, the recently discovered ligand of LGR5. Here we show that Lgr5-lacZ is not expressed in healthy adult liver, however, small Lgr5-LacZ+ cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signalling. As shown by mouse lineage tracing using a new Lgr5-IRES-creERT2 knock-in allele, damage-induced Lgr5+ cells generate hepatocytes and bile ducts in vivo. Single Lgr5+ cells from damaged mouse liver can be clonally expanded as organoids in Rspo1-based culture medium over several months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into Fah−/− mice. These findings indicate that previous observations concerning Lgr5+ stem cells in actively self-renewing tissues can also be extended to damage-induced stem cells in a tissue with a low rate of spontaneous proliferation.
Anaplastic Lymphoma Kinase as a Cancer Target in Pediatric Malignancies
Authors: Yael P. Mossé
Journal: Clinical Cancer Research (2015)

Abstract In this era of more rational therapies, substantial efforts are being made to identify optimal targets. The discovery of translocations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase in a subset of non–small cell lung cancers has become a paradigm for precision medicine. Notably, ALK was initially discovered as the fusion gene in anaplastic large cell non-Hodgkin lymphoma, a disease predominantly of childhood. The discovery of activating kinase domain mutations of the full-length ALK receptor as the major cause of hereditary neuroblastoma, and that somatically acquired mutations and amplification events often drive the malignant process in a subset of sporadic tumors, has established ALK as a tractable molecular target across histologically diverse tumors in which ALK is a critical mediator of oncogenesis. We are now uncovering the reexpression of this developmentally regulated protein in a broader subset of pediatric cancers, providing therapeutic targeting opportunities for diseases with shared molecular etiology. This review focuses on the role of ALK in pediatric malignancies, alongside the prospects and challenges associated with the development of effective ALK-inhibition strategies. Clin Cancer Res; 22(3); 546–52. ©2015 AACR.