tbuckley/cabot-search huggingface dataset:
Expression of Interferon Regulatory Factor 4 in Chronic Myeloid Leukemia: Correlation With Response to Interferon Alfa Therapy
Authors: Manuel Schmidt, Andreas Hochhaus, Sven A. König-Merediz, Cornelia Brendel, Jutta Proba, Georg J. Hoppe, Burghardt Wittig, Gerhard Ehninger, Rüdiger Hehlmann, Andreas Neubauer
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-α) treatment in CML. MATERIALS AND METHODS: Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro–stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-α therapy and in 47 additional CML samples taken during IFN-α therapy. IRF4 expression was then correlated with cytogenetic response to IFN-α. RESULTS: IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-α therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-α therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-α, a good response was associated with high IRF4 expression. CONCLUSION: IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-α therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-α in CML.
Allergens from rye pollen (<i>Secale cereale</i>)
Authors: M. T. Montero, E. Alonso, T. Sainz
Journal: Allergy (1992)

We have studied the proteins and allergens released by rye pollen in the course of a 19‐h pollen incubation process. Nearly 40% of the total extracted proteins were collected during the first 5 min, and most of them had a molecular weight &lt;28 kDa. Between 5 and 30 min, 15% of the proteins from total extract were released, showing in the SDS‐PAGE analysis an increase in which components moved close to 30 kDa standard. From 30 min to 19 h several extracts were collected. Electrophoretical profile of components from these extracts reveals that bands moving below 28 kDa were practically absent and those of 28 and 23 kDa became very intense. At the end of the process there was a rise of 67 kDa proteins. Dot‐immunobinding and immunoblotting techniques reveal that allergens leave the rye pollen, for the most part, after 5 min incubation and are proteins with 28 kDa, 33 kDa, 48 kDa and 67 kDa molecular weights.
Law makers question science behind US dietary guidelines
Authors: Michael McCarthy
Journal: BMJ (2015)

Skeptical law makers in the United States questioned Sylvia Burwell, US health and human services secretary, and Tom Vilsack, agriculture secretary, about the science behind and effectiveness of the US dietary guidelines in a three hour hearing before the US House Commitee on Agriculture on 7 October.

The departments of health and human services and agriculture are mandated by Congress to publish a report entitled Dietary Guidelines for Americans at least every five years. The guidelines have a widespread impact, influencing nutrition programs, food labeling, and research priorities.

The guidelines came under fire earlier this year after an expert panel released its recommendations for updating the …
Maternal Age and Breast Cancer Risk
Authors: John A. Baron, Martin Vessey, Klim McPherson, David Yeates
Journal: JNCI Journal of the National Cancer Institute (1984)

Maternal age at time of birth was investigated as a risk factor for breast cancer in a study of 1,176 matched case-control pairs. There was no pattern of increasing adjusted relative risk of breast cancer with increasing maternal age, nor was the mean maternal age of cases older than that of controls. Similar negative results were found among the subset of subjects up to 35 years old, a group previously found to show marked maternal age effects. Thus previous reports of an association between breast cancer and advanced maternal age may have been due to chance, extraneous factors, or a misleading reliance on unadjusted mean maternal ages, rather than on relative risks.
Effect of low-dose prophylactic dopamine on high-dose cisplatin-induced electrolyte wasting, ototoxicity, and epidermal growth factor excretion: a randomized, placebo-controlled, double-blind trial.
Authors: G Somlo, J H Doroshow, A Lev-Ran, D C Ahn, L Hwang, J W Raschko, S J Forman, K A Margolin, R J Morgan, L A Leong
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the protective effect of low-dose dopamine given as continuous infusion in patients who undergo chemotherapy with the nephrotoxin cisplatin. PATIENTS AND METHODS Forty-two patients who received high-dose cisplatin-containing chemotherapy entered a prospective, randomized, double-blind, placebo-controlled trial. Twenty-one patients received dopamine, and 21 received placebo. Patients were to receive either infusional dopamine 2 micrograms/kg/min over 48 hours or placebo. Cisplatin 125 mg/m2 was administered 12 hours after initiating dopamine (group D) or placebo (group P). This schedule was repeated twice, 1 week apart. Measurements of serum creatinine, urinary electrolytes and creatinine, urinary excretion of epidermal growth factor (EGF), ototoxicity, parameters of hematopoietic recovery, and duration of hospitalization were analyzed. RESULTS We observed an increase in serum creatinine level to a peak of 1.9 mg/dL (range, 0.8 to 7.8) in the dopamine group, in comparison to 1.4 mg/dL (range, 0.9 to 3.3) in the placebo group (P = .04). Urinary magnesium excretion increased and EGF excretion decreased in both groups. Urinary sodium, chloride, and potassium excretion were increased in both groups, but more so in the placebo group. Dopamine had no measurable effect on hearing loss, duration of hospitalization, or hematopoietic recovery. CONCLUSION The use of prophylactic dopamine increased peak serum creatinine levels relative to placebo and failed to prevent cisplatin-induced renal toxicity or ototoxicity. Determination of whether dopamine could reverse chemotherapy-induced renal damage would require a randomized prospective trial.
Combined modality therapy for tumor stage mycosis fungoides: results of a 10-year follow-up.
Authors: D E Hallahan, M L Griem, S F Griem, M Medenica, K Soltani, A L Lorincz, J M Baron
Journal: Journal of Clinical Oncology (1988)

Twenty-one patients with tumor stage mycosis fungoides (MF) with or without lymph node (LN) involvement, were treated with total skin electron beam irradiation (TSEB) followed by six monthly cycles of systemic chemotherapy (CT) of either mechlorethamine (HN2) or cyclophosphamide (CTX) with vincristine (VCR), procarbazine, and prednisone (PRD) (COPP or MOPP). All patients had complete clearing of the skin after TSEB. However, while receiving chemotherapy, two patients developed visceral involvement and eight patients relapsed with limited cutaneous plaques (LCP). The median duration of remission was 12 months from the completion of TSEB, and all patients relapsed with cutaneous plaques within 25 months. Complete remission was again achieved using additional electron irradiation and maintenance therapy in all but one patient. Multiple cutaneous recurrences occurred in all patients. Median survival from the initiation of TSEB is 6 years. Five patients are living beyond 8 years (four off treatment without disease for 1 to 7 years). LN involvement did not influence initial response or survival. Combined modality therapy for tumor stage MF using TSEB followed by systemic CT and subsequent maintenance therapy may lead eventually to prolonged disease-free survival (DFS) in selected patients.
Nerve Growth Factor Gene Therapy
Authors: Mark H. Tuszynski, Jennifer H. Yang, David Barba, Hoi-Sang U, Roy A. E. Bakay, Mary M. Pay, Eliezer Masliah, James M. Conner, Peter Kobalka, Subhojit Roy, Alan H. Nagahara
Journal: JAMA Neurology (2015)

Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment.To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset.Patients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined.Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay.Among 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P < .05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes, with resultant activation of cell signaling. No adverse pathological effects related to NGF were observed.These findings indicate that neurons of the degenerating brain retain the ability to respond to growth factors with axonal sprouting, cell hypertrophy, and activation of functional markers. Sprouting induced by NGF persists for 10 years after gene transfer. Growth factor therapy appears safe over extended periods and merits continued testing as a means of treating neurodegenerative disorders.
Posterior chorioretinal atrophy and vitreous phenotype in a family with Stickler syndrome from a mutation in the COL2A1 gene11None of the authors has any proprietary interests in any materials used or data presented in this manuscript.
Authors: Cuong D Vu, Jeremiah Brown, Jarmo Körkkö, Robert Ritter, Albert O Edwards
Journal: Ophthalmology (2002)
Establishment and Immunologic Characterization of 3-Methylcholanthrene-Induced Sarcoma Cell Lines Metastasizing Widely in Mice and Exhibiting Distinct and Selective Propensities for the Mode of Metastasis&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Y Kodama, T Seyama, K Kamiya, K Yokoro
Journal: JNCI Journal of the National Cancer Institute (1982)

Successive transplantations of metastatic secondary tumors of a 3-methylcholanthrene-induced sarcoma in (C57BL/Ka X C3H/He)F1 male and female syngeneic mice resulted in the establishment of two unique tumor cell lines with enhanced metastatic potential. Moreover, each line showed distinct and selective propensities for the mode of metastasis. The 1101Pn tumor line, obtained by successive transplantations of metastatic pulmonary nodules, metastasized to many visceral organs via the bloodstream. Another tumor line, 1101Ln, selected by repeated transplantations of lymph node metastases, metastasized to almost all lymph nodes and to the lungs. When the metastatic pulmonary tumor of mice bearing 1101Ln was subcutaneously implanted on the backs of syngeneic mice, the tumor grew locally and eventually metastasized via the lymphatics, with systemic involvement of the lymph nodes. This finding is an indication that the intrinsic properties of tumor cells that form pulmonary metastases in 1101Ln tumor-bearing mice are distinct from those in 1101Pn tumor-bearing mice in terms of metastatic mode. The 1101Pn and 1101Ln tumor lines were nonimmunogenic or less immunogenic than the 505 tumor (the parental, nonselected tumor line). The growth and metastatic action of 505 tumors were enhanced by 400 R whole-body X-radiation, but no such effect was seen with 1101Pn tumors. Pretreatment of mice with OK-432, an immunopotentiator, retarded the growth and metastasis of 505 tumors but exerted little or no effect on 1101Pn tumors. The experimental results suggest that a tumor is composed of a heterogeneous cell population with respect to metastatic potential, metastatic mode, and tumor immunogenicity and that some intrinsic properties of the tumor cell have a primary role in the determination of the mode of cancer metastasis.
Identification and characterization of two ankyrin-B isoforms in mammalian heart
Authors: Henry C. Wu, Gokay Yamankurt, JiaLie Luo, Janani Subramaniam, Syed Shahrukh Hashmi, Hongzhen Hu, Shane R. Cunha
Journal: Cardiovascular Research (2015)

AimsExcitation–contraction coupling in cardiomyocytes requires the proper targeting and retention of membrane proteins to unique domains by adaptor proteins like ankyrin-B. While ankyrin-B has been shown to interact with a variety of membrane and structural proteins located at different subcellular domains in cardiomyocytes, what regulates the specificity of ankyrin-B for particular interacting proteins remains elusive.
Childhood Hodgkin's disease: patterns of relapse.
Authors: K J Russell, S S Donaldson, R S Cox, H S Kaplan
Journal: Journal of Clinical Oncology (1984)

One hundred seventy-nine consecutive children with Hodgkin's disease seen at Stanford University Medical Center between the years 1961-1980 have been analyzed for survival and freedom-from-relapse as a function of clinical versus laparotomy staging as well as primary treatment modalities. Of laparotomy-staged patients, 86% are alive at 10 years after primary radiation with chemotherapy reserved for relapse, as compared with 90% managed by planned combined modality therapy (p = 0.62). Patients who were clinically staged and managed with primary radiation have only a 69% survival (p = 0.05). A favorable subgroup of patients with lymphocyte-predominant Hodgkin's disease experienced a low relapse rate regardless of primary treatment modality. Patterns of relapse in clinically staged patients reflect understaging, with most relapses in distant, nonirradiated sites, whereas the less frequent relapses in laparotomy-staged patients usually reflect regional recurrence. It is concluded that laparotomy staging is highly desirable to allow greatest flexibility in optimizing individual therapy. Routine combined modality treatment for all patients would overtreat certain favorable subgroups, who can be managed more conservatively as long as the information derived from surgical staging is available. For young children, in whom bone growth issues are paramount, combined modality treatment using low-dose radiation is recommended. For older children and adolescents, where concerns over chemotherapy-related leukemogenesis and infertility are more important than height considerations, radiation alone may be used for stages I-IIIA with equal overall success.
Kinetics of Depression and Recovery of Murine Hepatic Cytochrome P-450 Levels After Treatment With the Interferon Inducer Polyriboinosinic-Polyribocytidylic Acid&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: D O Crowe, J J Reiners, D E Nerland, G Sonnenfeld
Journal: JNCI Journal of the National Cancer Institute (1986)

In vivo treatment of randombred Swiss Webster mice with polyriboinosinic-polyribocytidylic acid (poly I·poly C) inhibited the induction of cytochrome P-450's by both 3-methylcholanthrene [(MCA) CAS: 56-49-5] and phenobarbitol [(PB) CAS: 50-06-6]. Concomitant treatments with poly I·poly C and a single dose of MCA inhibited the induction of P-450's for 24 hours and delayed the obtainment of the MCA-induced P-450 levels for approximately 48–72 hours. When cytochrome P-450 levels were induced by four successive daily treatments of MCA or PB and when poly I·poly C was given on only the 1 st day, induction of P-450's was completely suppressed for 24 hours and obtainment of the maximal P-450 level was delayed by 72–96 hours. Treatment with poly I·poly C of animals preinduced for P-450's by four successive daily treatments with either PB or MCA decreased the P-450 content to the noninduced basal level within 24 hours. The effect was temporary in the MCA-treated mice since P-450 content recovered to the MCA-preinduced levels within 72 hours. PB-dependent P-450 induction was short lived, and no recovery occurred after poly I·poly C treatment of PB-preinduced mice. Reduced hepatic cytochrome P-450 contents correlated with decreased abilities of liver homogenates to metabolically activate benzo[a]pyrene (CAS: 50-32-8) and N-acetyl-2-aminofluorene (CAS: 53-96-3), as scored in an Ames Salmonella typhimurium revertant assay.
Hepatic expression of interleukin 8 in diagnosing biliary atresia
Authors: Rui Dong, Gong Chen, Shan Zheng, Harry Hua‐Xiang Xia
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Bessho et al., who demonstrated that, among the 15 genes uniquely expressed in the liver of patients with biliary atresia (BA), IL8 and LAMC2 were sufficient to distinguish subjects with BA from patients with non‐BA controls, with an accuracy of 95%.1 They conclude that hepatic expression of these two genes may serve as a biomarker of disease. Whereas we appreciate the findings, we would like to address a few issues that may help further clarify or confirm the findings. First, only 14 patients were included as non‐BA controls; the causes of disease were unknown for 64.3% (n = 9) (Supporting Table 1 of Bessho et al.). Moreover, 21.4% (n = 3) of the non‐BA controls were misclassified by IL8 and LAMC2 as BA (Supporting Table 2 of Bessho et al.). It is conceivable that some non‐BA diseases share a similar genetic signature or phenotypic traits with BA, and exhibit similar hepatic expression profiles. Indeed, as previously demonstrated, the IL‐8 level is higher in the BA and non‐BA groups than in normal controls, and the increased IL‐8 level is associated with the lymphocytic count and the degree of fibrosis in BA.2 Also, it has been known that viral infection can promote IL‐8 expression in the liver, which is associated with chronic liver disease.5 Thus, subjects with virus infection in the non‐BA groups might have a similar level of hepatic IL‐8 expression, compared with those in the BA group. In the present study, whether the false positivity by IL8 and LAMC2 observed in three patients in the non‐BA group was associated with infections with viruses such as rotavirus, cytomegalovirus, etc. is unknown. Second, it has been reported that IL‐8 mRNA increases in the liver, particularly in the late stage of BA (e.g., the degree of fibrosis represented by aspartate aminotransferase‐to‐platelet ratio index) and advanced age, and is associated with persistent jaundice, portal hypertension, and/or an increased inflammation and fibrosis in the liver.3 Thus, it is recommended that the patients included in the study be divided into different groups according to the degree of fibrosis (e.g., aspartate aminotransferase‐to‐platelet ratio index) and age (e.g., ≤60, 61‐90, and > 90days). Therefore, it would be interesting if Bessho et al. were to reassess their data by taking viral infection, the degree of fibrosis, and age into account. Alternatively, a larger case‐controlled study incorporating the above‐mentioned points is required.
Use of high flow nasal oxygen (HFNO) for bronchiolitis in a general paediatric ward: Preliminary experiences
Authors: Maggie Hufton, Gerard Millen, Chetna Kallappa, Titus Ninan
Journal: European Respiratory Journal (2012)

Background  Viral bronchiolitis is a leading cause of hospitalisation. Interventions to reduce morbidity are challenging. We evaluated HFNO in infants with acute bronchiolitiis on a general paediatric ward. Previous HFNO experience has been in a PICU or HDU settings.  Aim: To assess responses to HFNO in previously well children and in those with underlying co morbidities.  Methods: Prospective study between November 2011 and February 2012. Inclusion criteria were patients needing >30% Fi02 or a RR(respiratory rate)≥60/ minute.  Results: Nine previously well infants, mean age 40 days (range 10-120 days) were commenced on HFNO. Mean RR and pulse rate prior to initiating HFNO was 73 and 146 respectively. Mean oxygen requirement was 37%. 5 patients had observations done before 2 hours and then between 2-4 hours. A reduction in mean RR to 54 at 2 hours and 47 at 4 hours was observed. The mean pulse rate reduced to 132 and 102. Mean oxygen requirement was higher at 2 hours (43%) but reduced at 4 hours (32%). No significant change in blood gases noted. 8 children responded well to HFNO. One patient required nasal CPAP.  Five children with underlying co morbidities and acute bronchiolitis were started on HFNO. These children were older, mean age 270 days (range 60-630). Of these 5, 3 deteriorated on HFNO and required escalating interventions.  Conclusion: In previously well infants with bronchiolitis, HFNO is safe in a general paediatric ward setting and offers clinical benefits within 2-4 hours. Children with underlying disorders may not respond as well and if no improvement is seen within 4 hours, stepping up treatment may be desirable.
Diagnostic Dilemmas in Oncology
Authors: Glen D. Raffel, Ellen M. Gravallese, Pascale Schwab, Jeffery T. Joseph, Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.23.4341 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11731518 Diagnostic Dilemmas in Oncology Case 2. Dermatomyositis and Ovarian Cancer Glen D. RaffelxGlen D. RaffelSearch for articles by this author , Ellen M. GravallesexEllen M. GravalleseSearch for articles by this author , Pascale SchwabxPascale SchwabSearch for articles by this author , Jeffery T. JosephxJeffery T. JosephSearch for articles by this author , Stephen A. CannistraxStephen A. CannistraSearch for articles by this author Show More Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2001.19.23.4341 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology