tbuckley/cabot-search huggingface dataset:
Growth and Regrowth of an Autogenous Rat Sarcoma: Effects of Nitrogen Mustard2
Authors: Joseph Post, Robert J. Sklarew, Joseph Hoffman
Journal: JNCI Journal of the National Cancer Institute (1975)

Immediate and delayed effects of nitrogen mustard (HN2) (0.1 mg/kg/day for 4 days) on the growth and cell proliferation patterns of the 3-methylcholanthrene-induced autogenous rat sarcoma were studied. Tumor cells were labeled continuously with 0.5 μCi tritiated thymidine/g for 24 hours. The labeling index fell from 36.4 to 14.0% and the mitotic index from 0.88 to 0.67% after two treatments with HN2. At that time, tumor growth stopped and remained arrested during HN2 adminisration. After four injections of HN2, the labeling index was reduced further to 0.73% and the mitotic index to 0.36%. After the drug was withdrawn, tumor growth resumed at the pretreatment rate, even though the labeling index on day 3 was only 15.5% (or 40% of the control). The percent labeled mitosis curves and DNA contents, before and 4 days after HN2 was given, were similar. It was concluded that a subpopulation of cells of predominantly short intermitotic times caused tumor growth before and after drug treatment.
Government’s pledges on mental health are not backed with funding, says spending watchdog
Authors: Anne Gulland
Journal: BMJ (2016)

The cost of implementing the government’s plans to improve mental health services is not fully understood, says a report by the National Audit Office, which examines public spending for UK parliament.1

As part of the government’s commitment to giving mental health “parity of esteem” with physical health, it set out waiting time standards for mental health services and said it would improve access to psychological therapies, early intervention in psychosis, and liaison psychiatry.

However, the costs of improving waiting times and access are unclear, the report found. The Department of Health in England said that the cost of improving access could be £160m ($230m; €200m) a year more than the £663m that clinical commissioning groups spent on these services during 2014-15. But the …
Sustained Remission of Nelson's Syndrome after Stopping Cyproheptadine Treatment
Authors: Neil Aronin, Dorothy T. Krieger
Journal: New England Journal of Medicine (1980)

Cyproheptadine treatment in some patients with Cushing's disease or Nelson's syndrome results in amelioration of the clinical symptoms, a decrease in the range of plasma levels of adrenocorticotropin (ACTH), restoration of normal periodicity of plasma concentrations of ACTH, and reversal of the anomalous ACTH response to thyrotropin releasing hormone.1 2 3 4 Such treatment is based on cyproheptadine's antiserotoninergic actions, since serotonin has a role in the release of corticotropin releasing factor5 and in the mediation of circadian periodicity of corticosteroid concentrations.6 Relapse occurs when the drug is discontinued.1 In this report, we describe a patient with Nelson's syndrome in whom clinical and . . .
Questionable Reliability of the Polymerase Chain Reaction in the Detection of Mycobacterium Tuberculosis
Authors: Gerda T. Noordhoek, Jan D.A. van Embden, Arend H.J. Kolk
Journal: New England Journal of Medicine (1993)

To the Editor: Conventional methods of detecting Mycobacterium tuberculosis in clinical samples, such as microscopy or culture, are either low in sensitivity and specificity or time-consuming. The ...
In Vitro Growth Stimulation of Human Ovarian Cancer Cells by Xenogeneic Peritoneal Macrophages<xref ref-type="fn" rid="fn2">2</xref><xref ref-type="fn" rid="fn3">3</xref><xref ref-type="fn" rid="fn4">4</xref>
Authors: C E Welander, R B Natale, J L Lewis
Journal: JNCI Journal of the National Cancer Institute (1982)

For improvement of the in vitro growth rate of human ovarian tumors, an irradiated xenogeneic feeder layer of adherent peritoneal cells was added to such cultures. This adherent peritoneal cell population was obtained from oil-primed adult (C57BL/6J x DBA/2J)F1 mice and contained predominantly macrophages. After irradiation of the feeder layer with 3,000 rad 137Cs, cell suspensions prepared from fresh, solid human ovarian cancers were cocultivated with the feeder cells. Two end points were used to evaluate the growth enhancement added by such a feeder layer: 1) Primary monolayer cultures of ovarian tumors were successfully grown in continuous culture through five or more serial subcultures in 25 of 64 different patient specimens studied. Control cultures without the feeder layers did not continue growing through serial subcultures. 2) With the use of the soft agar clonogenic assay, addition of the feeder layer to the petri dishes increased the number of tumor cell colonies in each of six separate experiments, compared to the number seen in control plates without the feeder layer.
Passive Transfer of Tuberculin Sensitivity to Patients with Sarcoidosis
Authors: Frederick Urbach, Maurice Sones, Harold L. Israel
Journal: New England Journal of Medicine (1952)

STUDIES in various countries agree that approximately two thirds of patients with sarcoidosis fail to react to second-strength tuberculin — 0.005 mg. of Purified Protein Derivative (PPD) or 1.0 mg. of Old Tuberculin (OT).1 2 3 The failure to react is not merely the result of absence of exposure to tuberculous infection, since patients with sarcoidosis proved unable to develop and maintain tuberculin sensitivity in normal fashion after BCG vaccination.2 , 3 This diminished reactivity to tuberculin has been interpreted as evidence both for3 and against1 a tuberculous etiology of sarcoidosis. Two main theories have been proposed to explain this phenomenon:"Positive anergy" is . . .
Heterogenous Inflammation in Chronic Rhinosinusitis without Nasal Polyps
Authors: Atsushi Kato, Aiko I. Klingler, Whitney W. Stevens, Anju T. Peters, Julie A. Poposki, Lydia Suh, James E. Norton, Roderick G. Carter, Kathryn E. Hulse, Leslie C. Grammer, Robert P. Schleimer, Stephanie S. Smith, David B. Conley, Robert C. Kern, Bruce K. Tan
Journal: Journal of Allergy and Clinical Immunology (2016)
Nonmalignancy of Hybrids Derived From Two Mouse Malignant Cells. I. Hybrids Between L1210 Leukemia Cells and Malignant L Cells 2
Authors: Jacques Jami, Evelyne Ritz
Journal: JNCI Journal of the National Cancer Institute (1973)

Cl 1D cells, a subclone of L cells, derived from a C3H mouse, produced tumors in 17% of compatible mice. L1210 leukemia cells, derived from a DBA/2 mouse, were highly malignant and killed 100% of hosts. Four independent hybrid clones (YC), derived from the fusion of Cl 1D and L1210 cells, failed to induce any tumor in (DBA/2 × C3H)F1 compatible mice. These observations suggest that malignancy was suppressed in hybrid cells by complementation. However, although YC hybrids did not produce tumors, they nevertheless had in vitro characteristics of malignant cells and parental tumor antigens. Histocompatibility factors between somatic hybrids and F1 mice are discussed.
Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis
Authors: Guido V. Bloemberg, Peter M. Keller, David Stucki, Andrej Trauner, Sonia Borrell, Tsogyal Latshang, Mireia Coscolla, Thomas Rothe, Rico Hömke, Claudia Ritter, Julia Feldmann, Bettina Schulthess, Sebastien Gagneux, Erik C. Böttger
Journal: New England Journal of Medicine (2015)

Treatment of multidrug-resistant Mycobacterium tuberculosis is a challenge. This letter describes the emergence of resistance to new therapies, bedaquiline and delamanid.
S8 A nationwide real-life study: Exploring the difficulties of confirming the asthma diagnosis in patients with severe asthma
Authors: A von Bülow, V Backer, U Bodtger, NU Soes Petersen, T Skjold, K Dahl Assing, C Porsbjerg
Journal: Thorax (2015)

<h3>Introduction</h3> Many conditions may mimic severe asthma. Therefore, patients with asthma who receive high dose asthma therapy are recommended to undergo systematic evaluation in order to objectively confirm the diagnosis of asthma. <h3>Aims and objectives</h3> To evaluate to which extent patients treated by respiratory specialists for severe asthma had the diagnosis of asthma verified by the demonstration of variable airflow obstruction. <h3>Methods</h3> A retrospective cross-sectional study was performed in 2013. Patient record forms of all patients (18–65 years) newly referred to one of five respiratory outpatient clinics in Denmark in the period of 2009–2010 with a diagnose of asthma (ICD-10: DJ45-DJ459) were screened after a two-year observation period for having severe asthma. Patients were included in the study, if they had a doctors diagnosis of asthma and received inhaled corticosteroids equivalent to ≥1600 μg budesonide and a second controller (long acting beta-2-agonist, theophylline or leukotriene-antagonist) for a minimum of twelve months or were treated with oral prednisolone (minimum six months). Diagnostic tests for asthma were registered: Day-to-day PEF monitoring, reversibility test (short-acting beta-2-agonist or prednisolone) and bronchial challenge test (methacholine, mannitol, exercise test, eucapnic voluntary hyperpnoea test). <h3>Results</h3> A total of 1417 newly referred subjects were screened, of whom 98 patients fulfilled the above criteria of having severe asthma. Overall, 84% were assessed with at least one diagnostic test: Reversibility test 63%, PEF monitoring 57% and bronchial challenge test 21%. In total, 50% of the study population had at least one positive diagnostic test; 37% had a positive reversibility test, 17% had significant peak flow variation and 12% had a positive bronchial challenge test. Among those having negative reversibility test or negative peak flow measurements with FEV1≥70%, only 30% had a bronchial challenge test performed. <h3>Conclusion</h3> Among patients managed for severe asthma in five specialist hospital clinics in Denmark, only half had the asthma diagnosis confirmed objectively. This indicates a substantial room for improvement in order to ensure that patients receiving high dose asthma therapy truly have asthma.
Case 1-2000
Authors: Philip W. Kantoff, Esther Oliva
Journal: New England Journal of Medicine (2000)

PrefaceThis millennial year is also a centennial year, and since the Case Records were conceived about a century ago, it is fitting to recount the circumstances of their origin on the occasion of the first Case Record of 2000. In its first issue of the 20th century, the Boston Medical and Surgical Journal, later to become the New England Journal of Medicine, published “The Case Method of Teaching Systematic Medicine” (1900;142:31-6), an article submitted by Walter B. Cannon, a senior student at Harvard Medical School who would later become the George Higginson Professor of Physiology at the medical school. . . .
Lymphocyte Stimulation Induced by Halothane in Patients with Hepatitis Following Exposure to Halothane
Authors: Fiorenzo Paronetto, Hans Popper
Journal: New England Journal of Medicine (1970)

Stimulation of lymphocytes, as measured by incorporation of 3H-thymidine into the deoxyribonucleic acid of lymphocytes, was observed in the presence of halothane in 10 of 15 patients with halothane hepatitis, but not in healthy controls, patients with hepatic disease or patients who were exposed to halothane but did not have liver damage. Lymphocytes of a patient with hepatic damage attributable to methoxyflurane were stimulated by methoxyflurane. Preliminary data indicate that sensitization is temporary. The plasma of the patients may contain a factor inhibiting lymphocyte stimulation. Australia antigen was not detected in the serums of the patients, but antimitochondrial antibodies seemed to correlate with lymphocyte stimulation. Stimulation of lymphocytes in the presence of halothane is helpful in the differential diagnosis of viral and halothane hepatitis, and indicates that in some patients, the anesthetic may be a sensitizing agent with a pathogenetic role in the hepatic damage.
DDEL-11SELECTIVE TARGETING OF GLIOBLASTOMA USING FOLATE-DECORATED NANO-PARTICULATE CYTOCHROME C DRUG CONSTRUCTS
Authors: Josue Davila, Kimberleve Rolon Reyes, Moraima Morales Cruz, Michael Inyushin, Yuriy Kucheryavykh, Kai Griebenow, Lilia Kucheryavykh
Journal: Neuro-Oncology (2015)

DDEL-11. SELECTIVE TARGETING OF GLIOBLASTOMA USING FOLATE-DECORATED NANO-PARTICULATE CYTOCHROME C DRUG CONSTRUCTS Josue Davila1, Kimberleve Rolon Reyes1, Moraima Morales Cruz2, Michael Inyushin1, Yuriy Kucheryavykh1, Kai Griebenow2, and Lilia Kucheryavykh1; UniversidadCentraldel Caribe,Bayamon,Puerto Rico; University of Puerto Rico, Rio Piedras, Puerto Rico BACKGROUND: Glioblastoma (GBM) is one of the most malignant forms of brain cancers due to resistance to chemoand radiotherapy, mostly caused by enhanced resistance to apoptosis. We propose the development of targeted apoptosis-inducing drugs for glioblastomatreatment andapprobationof these drugs in glioblastoma cell lines and animal model. We developed nano-sized protein particles containing cytochrome C (NPs). For targeted delivery of the drug specifically to GBM cells we decorated the drug nano-particles with the ligand folic acid (FA). Many GBMs express Proton Coupled Folate Transporters that provide selective internalization of the designed NPs. Protein drug stability problems were countered by covalently decorating the constructs with glycans. RESULTS: Confocal imaging revealed the specific up-take of FITC tagged FA-NPs by GL261 cells, but not by primary cultured astrocytes. Examination of live brain slices encompassing glioblastoma tumor showed some non-specific accumulation of NPs in healthy tissue in two hours after application of FA-NPs, but 20-times less compared to the tumorarea.NPs, used invitro inconcentration of100 mg/ml,havenocytotoxic effect in astrocytes but cause 40% death in tumor cells. The use of NPs in combination with LY294002 (PI3K/AKT blocker), 50 mM, caused 90% death in tumor cells. In vivo TUNEL investigation of tumors generated in C57Bl/6 mice by implantation of GL261 cells revealed the strong signs of apoptosis after three days of in-site administration of NPs through the microosmotic pumps without the evident signs of apoptosis in healthy tissue. In CONCLUSION: We can state that the designed NPs demonstrate good specificity for GL261 cells, effectively cause the apoptosis in these cells when used in combination with LY294002, and give a good baseline for the development of efficient methods for treating GBM. Acknowledgement: NIH Grant Numbers 1SC2GM102040-01A1, SC2GM095410-01A1, 8G12MD007583-27, R25GM110513, Title V grant number P031S130068. Neuro-Oncology 17:v73–v77, 2015. doi:10.1093/neuonc/nov212.11 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
HLA-DR Antigens and Toxic Reaction to Sodium Aurothiomalate and D-Penicillamine in Patients with Rheumatoid Arthritis
Authors: P. H. Wooley, J. Griffin, G. S. Panayi, J. R. Batchelor, K. I. Welsh, T. J. Gibson
Journal: New England Journal of Medicine (1980)

To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate of D-penicillamine, we studied 91 patients with rheumatoid arthritis. Seventy-one had toxic reactions to either drug or both drugs; the remaining 20 took one of the drugs for at least six months, without toxicity. Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRW3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinura and nine of 13 episodes of penicillamine-induced proteinura occurred in patients with these antigens. All 13 episodes of proteinuria in which urinary protein exceeded 2 g in 24 hours occurred in patients with DRw3. The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLA-DRw3 positive. No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications. Toxicity during aurothiomalate or penicillamine treatment for rheumatoid arthritis may be under genetic control.
Oocyte vitrification: A new approach for fertility preservation in cancer patients
Authors: A. Cobo, J. Domingo, P. Alamá, S. Pérez, J. Remohí, A. Pellicer, D. Almenar-Cubells
Journal: Journal of Clinical Oncology (2008)

20727 Background: Oocyte cryopreservation is a useful tool for fertility preservation in cancer patients at risk of losing the ovarian function due to the use of potentially sterilizing treatments. Results obtained with different cryopreservation protocols have been disappointing, particularly those obtained with slow cooling procedures. Vitrification has recently proven to be efficient enough to achieve its application in clinical practice. The aim of this study is to describe the results obtained with Cryotop method for oocyte vitrification in a population of oocytes recipients. Methods: Forty-seven donors and 57 oocyte recipients were included in this study. A total of 693 MII oocytes were collected after ovarian stimulation using long protocol down-regulation plus gonadotrophin administration. Vitrification was carried out by Cryotop method. Oocytes were donated to a proper recipient once the endometrial preparation was ready for the reception. Results: Of the 693 oocytes, 666 (96.1%) survived. A total of 487 (73.1%) were normally fertilized. The table shows clinical results. Conclusion: These results obtained in a population not affected by cancer show that oocyte cryo-banking, could be established realistically by applying the Cryotop vitrification method, offering excellent survival rates as well as a clinical outcome similar to the one obtained with fresh oocytes. Cancer patients could benefit from this approach for safeguarding their fertility, previous to the onset of the chemotherapy. Nº Embryo transfers 57 Embryos transferred (mean ± SD) 117 (1,99 ± 3,7) Pregnancy rate/transfer 36 (63.2) Implantation rate (Nºsacs/ Nº embryos transferred) 45 (38.5) Multiple pregnancy rate (twin) 11 (30.5) Miscarriage rate 6 (16.6) Biochemical pregnancy 5 (13.9) Ongoing pregnancy rate 25 (69.4) No significant financial relationships to disclose.
<i>MYC</i>-Driven Neuroblastomas Are Addicted to a Telomerase-Independent Function of Dyskerin
Authors: Rosemary O'Brien, Sieu L. Tran, Michelle F. Maritz, Bing Liu, Cheng Fei Kong, Stefania Purgato, Chen Yang, Jayne Murray, Amanda J. Russell, Claudia L. Flemming, Georg von Jonquieres, Hilda A. Pickett, Wendy B. London, Michelle Haber, Preethi H. Gunaratne, Murray D. Norris, Giovanni Perini, Jamie I. Fletcher, Karen L. MacKenzie
Journal: Cancer Research (2016)

Abstract The RNA-binding protein dyskerin, encoded by the DKC1 gene, functions as a core component of the telomerase holoenzyme as well as ribonuclear protein complexes involved in RNA processing and ribosome biogenesis. The diverse roles of dyskerin across many facets of RNA biology implicate its potential contribution to malignancy. In this study, we examined the expression and function of dyskerin in neuroblastoma. We show that DKC1 mRNA levels were elevated relative to normal cells across a panel of 15 neuroblastoma cell lines, where both N-Myc and c-Myc directly targeted the DKC1 promoter. Upregulation of MYCN was shown to dramatically increase DKC1 expression. In two independent neuroblastoma patient cohorts, high DKC1 expression correlated strongly with poor event-free and overall survival (P &amp;lt; 0.0001), independently of established prognostic factors. RNAi-mediated depletion of dyskerin inhibited neuroblastoma cell proliferation, including cells immortalized via the telomerase-independent ALT mechanism. Furthermore, dyskerin attenuation impaired anchorage-independent proliferation and tumor growth. Overexpression of the telomerase RNA component, hTR, demonstrated that this proliferative impairment was not a consequence of telomerase suppression. Instead, ribosomal stress, evidenced by depletion of small nucleolar RNAs and nuclear dispersal of ribosomal proteins, was the likely cause of the proliferative impairment in dyskerin-depleted cells. Accordingly, dyskerin suppression caused p53-dependent G1 cell-cycle arrest in p53 wild-type cells, and a p53-independent pathway impaired proliferation in cells with p53 dysfunction. Together, our findings highlight dyskerin as a new therapeutic target in neuroblastoma with crucial telomerase-independent functions and broader implications for the spectrum of malignancies driven by MYC family oncogenes. Cancer Res; 76(12); 3604–17. ©2016 AACR.
Changes in Plasma HIV-1 RNA and CD4+ Lymphocyte Counts and the Risk of Progression to AIDS
Authors: William A. O'Brien, Pamela M. Hartigan, David Martin, James Esinhart, Andrew Hill, Sharon Benoit, Marc Rubin, Michael S. Simberkoff, John D. Hamilton
Journal: New England Journal of Medicine (1996)

Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and β2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression.
The Relation of Megacolon and Megaloureter
Authors: Orvar Swenson, John H. Fisher
Journal: New England Journal of Medicine (1955)

IN the course of caring for a number of patients before and after operation for Hirschsprung's disease it became evident that some had defects in bladder function. To eliminate this as a postoperative complication, studies of bladder function became routine preoperatively on patients of sufficient age for the performance of satisfactory cystometrograms. Fifty per cent were found to have a bladder capacity greater than normal and diminished or absent detrusor contractions. These changes persisted after correction of the megacolon. Five per cent of these patients exhibited more severe bladder dysfunction, with large quantities of residual urine and high intravesical pressure, . . .
Brain Tumors as Second Malignancies in Children Treated for Acute Lymphoblastic Leukemia
Authors: M. Jankovic, G. Masera, M. L. Cristiani, E. Nardi, A. Arrighini
Journal: Neuro-Oncology (1991)

In the last years an increasing number of secondary tumors occurring many years after the discontinuation of treatment for ALL have been reported. Most frequently these tumors are localized in the brain and thyroid. Etiopathogenic factors remain unknown. Genetic predisposition and chemotherapy and/or radiotherapy previously administered are considered the most important issues. Cranial irradiation (CI) could play a major role in the development of brain tumors. In this paper the Italian experience in children with ALL is reported. Overall 12 solid tumors were observed in a population of 2080 children affected by ALL who discontinued any treatments within 12.31.1988. The data were obtained from the AIEOP-Off Therapy Registry, founded in 1980. Nine out of twelve were brain tumors and occurred between 3 and 10 years following cranial irradiation (24 Gy and/or 18 Gy). Six were Astrocytomas, two were Glioblastomas multiforme and 1 was an Oligodendroglioma. Only one child is still alive. The site of the tumor will be discussed. Further investigations should clarify: a)the risk of second neoplasms to the brain after ALL treatment within different treatment protocols with and without irradiation and b) the role of other factors (genetic predisposition, chemotherapy.........).