tbuckley/cabot-search huggingface dataset:
CD4 T-Helper Responses to the Anaplastic Lymphoma Kinase (ALK) Protein in Patients with ALK-Positive Anaplastic Large-Cell Lymphoma
Authors: Kamel Ait-Tahar, Martin C.N. Barnardo, Karen Pulford
Journal: Cancer Research (2007)

Abstract We have previously shown both humoral and CTL responses to anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large-cell lymphoma (ALCL). However, because CD4+ T-helper (Th) cells also play a vital role in developing and maintaining tumor immunity, we investigated the presence of a CD4+ Th response in ALK-positive ALCL. Using an IFN-γ ELISPOT assay, we identified two ALK-derived DRB1-restricted 24-mer promiscuous peptides, ALK1278–301 and ALK2233–256, as being immunogenic in six ALK-positive ALCL patients but not in two ALK-negative ALCL patients or five normal subjects. A significant interleukin-4 response to the ALK peptides was detected in only one ALK-positive patient. CD4+ Th cell lines lysed ALK-positive ALCL cell lines in a MHC class II–restricted manner. This first report of a CD4+ Th response to ALK provides valuable information for developing future immunotherapeutic options for ALK-positive ALCL patients who fail to respond well to conventional therapies. [Cancer Res 2007;67(5):1898–901]
Rebamipide (OPC-12759) in the Treatment of Dry Eye: A Randomized, Double-Masked, Multicenter, Placebo-Controlled Phase II Study
Authors: Shigeru Kinoshita, Saki Awamura, Kazuhide Oshiden, Norihiro Nakamichi, Hiroyuki Suzuki, Norihiko Yokoi
Journal: Ophthalmology (2012)
A natural killer cell granule protein that induces DNA fragmentation and apoptosis.
Authors: L Shi, R P Kraut, R Aebersold, A H Greenberg
Journal: The Journal of Experimental Medicine (1992)

We report the purification from a rat natural killer (RNK) large granular lymphocyte leukemia of a 32-kD granule protein that induces rapid DNA fragmentation and apoptosis. The protein, which we have called "fragmentin," was capable of causing DNA from intact YAC-1 cells to be cleaved into oligonucleosomal-sized fragments and producing severe chromatin condensation within 1 h. Amino acid sequence of tryptic peptides indicated that fragmentin was highly homologous to the NK and T cell granule serine proteases RNK protease 1 and mouse cytotoxic T cell protease I (CCPI)/granzyme B. Preincubation with the serine esterase inhibitor 3,4-dichloroisocoumarin blocked fragmentin-induced DNA damage, but had no effect on cytolysin. Fragmentin activity against four lymphoma target cells was completely dependent on the presence of cytolysin. Fragmentin produced rapid membrane damage as well as DNA fragmentation at nonlytic cytolysin doses, suggesting that fragmentin activity was not limited to its effects on the nucleus. Fragmentin and cytolysin activity were completely inhibited by EGTA, indicating the process was Ca2+ dependent. A role for cytolysin in endocytosis of fragmentin was suggested by the observation that treatment of YAC-1 with cytochalasin B or sodium azide and 2-deoxyglucose blocked DNA fragmentation but not cytolysin activity. A 30-kD N alpha-CBZ-L-lysine thiobenzyl esterase, which copurified with fragmentin, was inactive on its own but was able to synergistically amplify the DNA damage induced by fragmentin in the presence of cytolysin. Fragmentin activity was not dependent on protein synthesis, as cycloheximide treatment of YAC-1 cells did not prevent DNA damage. We postulate that fragmentin is the molecular mediator of NK cell-mediated DNA fragmentation and apoptosis.
Surgery or Radiotherapy?
Authors: John B. Graham
Journal: JAMA (1965)

Stage I lesions are of particular importance in cancer of the cervix because they are now found in more than half of all cases in our area. For example, in 1959, in New York state, excluding New York city, there were 749 cases of invasive cancer of the cervix. Of these, 424 (57%) were stage I. Although radiotherapy is generally regarded as the standard treatment of this disease, surgery is used in various localities for one of the following reasons: (1) in an impression that the results are as good as with radiotherapy; (2) in the hope that it will control the disease in those who cannot be cured by radiotherapy (this was the motive of Meigs<sup>1</sup>and is ours); (3) to obtain anatomical information about the disease; and (4) as a surgical exercise or educational measure. The relative effectiveness of radical surgery as compared with radiotherapy can be
Suggested approaches for research protocols involving the potential for life-threatening reactions
Authors: Daniel L. Hamilos, John J. Oppenheimer, Harold S. Nelson, Sally Wenzel, Sue Driscoll, Richard F. Lockey, David B.K. Golden, Leland Fan, Ralph J. Sanks, S.Allen Bock, John W. Yunginger, Donald Stevenson, Timothy Sullivan, Thomas Corbridge
Journal: Journal of Allergy and Clinical Immunology (1993)
Separation of myocardial cytoplasmic acidic inhibitor proteins which inhibit hepatic protein biosynthesis in vitro
Authors: Keith I. Gibson
Journal: Cardiovascular Research (1975)

Cytoplasmic inhibitor proteins of rabbit and pig myocardium have been separated and their in-vitro effects on hepatic cell-free protein biosynthesis reported. Three protein peaks could be separated from myocardial cytoplasmic pH 5 fraction by DEAE and CM cellulose column chromatography. There was a difference in the elution pattern of the acidic inhibitor proteins obtained from pig and rabbit myocardium. The myocardial acidic inhibitor proteins inhibited a liver cell-free protein biosynthesizing system, but not a myocardial cell-free system.
Exposure to antiandrogen during pregnancy: case report.
Authors: T Bergh, O Bakos
Journal: BMJ (1987)

Increased bacterial antibody titres-and IgA deficiency in epileptic patients An association between epileptic seizures and increased serum bacterial antibody titres was recently reported in Finnish patients receiving carba- mazepine and those receiving no drugs.'We studied bacterial antibody titres in Norwegian patients with epilepsy receiving long term treatment with phenytoin, many of whom had IgA deficiency.
Elective ventilation is cost effective and humane
Authors: H. Riad, A. Nicholls, C. Collins
Journal: BMJ (1995)

EDITOR,--We expected that our defence of elective ventilation1 would provoke criticism and wish to respond here to letters on the issue.2 Peter G M Wallace rightly says2 that the published experience of elective ventilation is limited to nine patients. The table summarises our full experience over six years. Two further patients became non-heart-beating donors as the relatives agreed to organ donation (and elective ventilation) but no intensive care unit bed was available. The 23 donors yielded 41 kidneys, two hearts, three sets of heart valves, one liver, and 20 corneas, which were transplanted with favourable outcomes.

Moving a patient back to a general medical ward does not create distress if the family members are supported: they consider that …
Abstract 4610: NO-NSAIDs inhibit colon tumor cell growth by a cGMP-independent mechanism
Authors: Evrim Gurpinar, Yanjie Sun, Adam Keeton, Heather Tinsley, Bernard Gary, Braeden L. Butler, Brock F. Binkowski, Levy Kopelovich, Mohammad Athar, Gary A. Piazza
Journal: Cancer Research (2011)

Abstract Nitric oxide-releasing NSAIDs (NO-NSAIDs) were originally developed as prodrugs to reduce the gastrointestinal toxicity of conventional NSAIDs and were found to have improved potency to inhibit tumor growth compared with the parent NSAID. Although different mechanisms have been proposed for their potent anticancer properties, the role of the NO-moiety has not been clearly defined. We have investigated whether the NO group contributes to the anticancer properties of NO-NSAIDs by inducing soluble guanylyl cyclase and elevating intracellular cGMP levels, effects that are associated with the activity of NO donors. We confirmed the increased potency of the NO-derivatives of sulindac, aspirin (o-, p- and m- isomers), exisulind and naproxen with respect to the parent compounds for inhibiting growth of HCT116, SW480 and COLO741 human colon tumor cells. The two derivatives with the lowest IC50 values, NO-sulindac (16.50 µM) and NO-ASA(o) (8 µM) were also tested for cGMP elevation using a novel cGMP biosensor assay in live cells. In brief, HEK293 cells were transfected with a biosensor construct containing cGMP binding domains fused to the modified firefly luciferase gene (Promega) which produces bioluminescence in the cGMP-bound or ‘activated’ state. Cells were treated with NO-Sulindac, NO-ASA(o) and known NO-donors, NOR-3 and SNP as positive controls. Chemiluminescence was measured over a period of 1h. A strong and sustained signal was obtained with the NO-donors, SNP and NOR-3 (50 µM), although no induction was observed with NO-NSAID treatment (50 µM). In addition, SW480 colon tumor cells were treated with 50 µM NO-Sulindac, NO-ASA(o) or NOR-3 and levels of phosphorylated vasoactivator stimulated phosphoproteins (p-VASP), an intracellular marker of cGMP signaling activity, were measured by Western Blotting. NOR-3 caused a time-dependent increase in p-VASP expression, whereas the NO-NSAIDs had no such effect. Since sulindac and certain derivatives have previously been reported to inhibit cGMP-phosphodiesterase (PDE) and inhibit tumor cell growth by a mechanism involving cGMP elevation, we also determined if NO-NSAIDS can inhibit cGMP PDE activity. NO-NSAIDs did not inhibit cGMP hydrolysis by either recombinant PDE5 or in lysates from colon tumor cells, although sulindac sulfide was an effective inhibitor as previously reported. These results suggest that mechanisms other than cGMP elevation explain the anticancer properties of NO-NSAIDs. Funding provided by NIH/NCI grants CA131378 and CA148817. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4610. doi:10.1158/1538-7445.AM2011-4610
Health of prisoners admitted to and discharged from Bedford Prison.
Authors: E Martin, M Colebrook, A Gray
Journal: BMJ (1984)

The age, smoking and drinking habits, active health problems, and occupational fitness of prisoners entering Bedford prison, and the health and willingness of prisoners being discharged from prison to take a letter to their general practitioner were surveyed. This group of men had a high level of illness, neglected their health, and had a high alcohol intake. Fewer problems were found than in a survey in New York City. Many prisoners with active medical problems on discharge from prison were unwilling to take a letter to their own general practitioner.
Tobacco tax to be ringfenced for NHS
Authors: L. Beecham
Journal: BMJ (1999)

Attention-deficit hyperactivity disorder (ADHD) in adults is understudied, especially regarding neural mechanisms such as oscillatory control of attention sampling. We report an EEG study of such cortical oscillations, in ADHD-diagnosed adults taking a continuous performance test that measures the ability to sustain attention and inhibit impulsivity for a prolonged period of time. We recorded 53 adults (28f, 25m, aged 18-60), and 18 matched healthy controls, using 128-channel EEG. We analysed features with established links to neural correlates of attention: event-related (de)synchronisation (ERS/D), alpha and theta frequency band activation, phase-locking value (PLV), and timing-sensitivity indices; in frontal and parietal scalp regions. Test performance distinguished healthy controls from ADHD adults. The ADHD group manifested significantly less parietal pre-stimulus 8Hz theta ERS during correct inhibition trials, less frontal &amp; parietal post-stimulus 4Hz theta ERS during inhibition &amp; response trials, and increased frontal &amp; parietal pre-stimulus alpha ERS during inhibition &amp; response. They showed significantly reduced fronto-parietal connectivity that lagged across trials and was strongly lateralised. In addition, they had reduced sensitivity to targets in stimulus-locking measures. Building on the hypothesis of parietal attention sampling, our results suggest that ADHD adults have impaired attention sampling in relational categorisation tasks.
British Medical Association at Belfast — Dangerous Drugs — Dr. Parkes Weber and Dr. Paul Wood
Authors: John Lister
Journal: New England Journal of Medicine (1962)

IN his presidential address at the annual meeting of the British Medical Association in Belfast in July, Mr. Ian Fraser, M.Ch., F.R.C.S., recalled that this was the fourth occasion on which the meeting had been held in Belfast. In 1884, at the time of the first meeting, great advances were taking place in medicine and surgery. The importance of micro-organisms in the causation of disease was just being appreciated, and successful surgery was being practiced with the help of anesthesia and the application of antiseptic and later aseptic technics. The doctor at that time was still visiting his patients in . . .
Colorectal Cancer Detection
Authors: Marvin M. Kristein
Journal: JAMA (1981)

<h3>To the Editor.—</h3> I wish to refer to the article "Colorectal Cancer Detection in a Community Hospital Screening Program" (1980;243:2056) by John E. Kurnick, MD, and co-workers. In his editorial comments in the same issue, Charles B. Clayman, MD, points out that we must consider whether the "expense of mass screening coupled with other costs created by methods of limited sensitivity and specificity outweigh the benefits." Since this is a critical point in the evaluation of various procedures, I should like to address the analysis of the outcomes reported in this (relatively) small sample of 5,420 persons who participated in Hemoccult slide testing. The discussion in the article speaks of a 40% failure rate for the Hemoccult slide method, which, as I will point out, is misleading. Final examination of the 5,420 participants in the Hemoccult slide testing, which was conducted on a less than optimal protocol basis (eg, "our
Nuclear Medicine: An Introductory Text
Authors: Martin L. Nusynowitz
Journal: JAMA (1982)

This concise volume, easily read in two or three evenings, provides an overview of nuclear medicine as currently practiced. It briefly describes most of the commonly employed imaging and physiological procedures and their applicability and limitations in diagnosis and therapy. The authors intend the primary audience to be practitioners applying nuclear medical procedures to patient care, but the book is also aimed at paramedical professionals (medical physicists, radiopharmacists, technologists) who must gain insight into the clinical applications of their work. The medical student would also find this an eminently suitable basic text. The first two chapters comprise simplified, brief, and well-illustrated outlines of the essential aspects of instrumentation and radiopharmaceuticals. They are sufficiently detailed to provide understanding of the principles involved but brief enough to avoid submerging the reader in a morass of technological minutiae. Several chapters are devoted to principles of radioimmunoassay, radionuclide therapy, and radiation safety, and the
Review of Lundy Braun,<i>Breathing Race Into the Machine: The Surprising Career of the Spirometer From Plantation to Genetics</i>
Authors: Jonathan Kahn
Journal: The American Journal of Bioethics (2015)

"Review of Lundy Braun, Breathing Race Into the Machine: The Surprising Career of the Spirometer From Plantation to Genetics." The American Journal of Bioethics, 15(2), pp. W5–W6
A pet prescription
Authors: D. Spence
Journal: BMJ (2008)

He lay curled up in a filthy box at the back of the cattle shed with his six brothers and sisters. As we approached he yelped loudly and wagged his tail—and thus he chose us and we chose him. His mother was a working border collie, and the farmer disapproved of his becoming a “pet.” He grew up with us. He herded the chickens, tagged along on marches through the fields, waited for the school bus, ate titbits under the table, danced with us to the …
SYMPTOM-TO-BALLOON TIME INTERVAL DELAYS IN ST-ELEVATION PATIENTS TRANSFERRED FROM DIFFERENT DISTANCES
Authors: Sa'ar Minha, Joshua Loh, Lowell Satler, Israel Barbash, Danny Dvir, Itsik Ben-Dor, Salem Badr, Lakshmana Pendyala, Hironori Kitabata, Kenneth Kent, Augusto Pichard, William Suddath, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2013)
How can risk reduction and early detection of SBP in cirrhotic ascites be improved?
Authors: G. A. D. Major, R. Ingram, A. Chivinge, M. James
Journal: Gut (2011)

<h3>Introduction</h3> UK incidence of cirrhosis and hospital admissions to treat complications is increasing. Spontaneous bacterial peritonitis (SBP) results in decompensation or death in over 40% at 90 days. Cirrhotic patients requiring large-volume paracentesis are at significant risk of developing SBP. Identifying those at high risk and screening for infection provide opportunities to intervene to prevent liver-related morbidity and mortality. The authors examined clinical practice and yield from these strategies. <h3>Methods</h3> Between July 2009 and June 2010, all patients undergoing day case large-volume paracentesis for cirrhotic ascites were identified. Patient demographics, aetiology, MELD and UKELD scores were recorded. Ascitic albumin, total white cell count (WCC) and culture was recorded when performed. SBP was diagnosed either by a total ascitic WCC &gt;500×10<sup>6</sup>/ml1 or positive culture. Outcome was determined for patients with SBP including <i>Clostridium difficile</i>-associated diarrhoea. <h3>Results</h3> 137 drains in 45 patients were performed over 12 months. 39 were male; median age was 54 (range 35–83). Mean (±SD) number of drains was 3.0 (±2.8). Aetiology was alcoholic liver disease (ALD) in 32 (71%), HCV in 5 (11%), HCV/ALD in 1, PBC in 1, NASH in 1 and other/cryptogenic in 5. Median MELD and UKELD were 23 and 51 respectively. 23/24 patients tested had baseline ascitic albumin &lt;10 g/l. Of these, 4 were on secondary and 1 on primary antibiotic prophylaxis. 47 (34%) had sampling; WCC from 44 drains, culture from 36 and 33 both. 7 samples (15%) were positive for SBP (4 raised WCC, 2 culture, 1 both). No patients were taking prophylaxis. 5 were subsequently admitted within 30 days for liver-related complications including sepsis and variceal haemorrhage, and 2 died within 90 days. In all, 16 (36%) died, 4 (9%) received and 4 (9%) are awaiting liver transplantation. 1 patient developed <i>C difficile</i>-associated diarrhoea following ciprofloxacin secondary prophylaxis. <h3>Conclusion</h3> Screening for SBP infection or risk was not universal. Over 90% of patients tested met criteria for consideration of primary prophylaxis. 15% of patients screened had SBP with a high rate of liver-related morbidity and mortality. Patients in paracentesis programmes should be actively considered for primary SBP prophylaxis, screened for SBP, and considered for liver transplantation or end-of-life planning.
Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone
Authors: W. L. Betsill
Journal: JAMA (1978)

A follow-up period averaging 21.6 years was obtained for patients with low-grade papillary intraductal carcinoma initially treated only by biopsy between 1940 and 1950. Subsequent carcinoma was diagnosed in the same breast in seven of the ten patients after an average interval of 9.7 years. Six of the seven subsequent carcinomas were invasive. Two of the patients died of metastatic carcinoma and two were known to be alive with metastases when last contacted. Three patients were without carcinoma following mastectomy. When these results were combined with the few reports available in the literature, it appeared that at least 39% of patients with intraductal carcinoma treated by biopsy alone subsequently had clinically evident carcinoma, invariably in the same breat, with an average latent period of about ten years. This was undoubtedly a result of the multicentric nature of the disease in many patients.
Long-Term Follow-up Study of Compensated Low-Dose<sup>131</sup>I Therapy for Graves' Disease
Authors: Vitaya Sridama, Maureen McCormick, Edwin L. Kaplan, Renee Fauchet, Leslie J. DeGroot
Journal: New England Journal of Medicine (1984)

We treated 187 patients who had Graves' disease with low-dose radioactive iodide (131I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after 131I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose 131I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with 131I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism. (N Engl J Med 1984; 311:426–32.)
Primary care trusts must "challenge the fiction of the wonder drug"
Authors: L. Hitchen
Journal: BMJ (2008)

Primary care trusts need to “challenge the fiction of the wonder drug,” a conference on the organisation of the NHS was told last week.

Sophia Christie, chief executive of Birmingham East and North Primary Care Trust, said, “This fiction is a really dangerous one that we need a more sophisticated understanding of.” Media headlines describe some drugs as “lifesaving treatments,” when they often prolonged survival only for a number of weeks.

Many patients did not understand the numbers, she told the conference held at the Royal College of Physicians, and commissioning should not be driven by the demands of patients and clinicians. Giving patients these products only delayed discussions with patients about end of life care, an issue that, she said, needs an open debate and radical change.

Ninety per cent of healthcare spending goes on …
CIRCUMFLEX ARTERY RELATED MYOCARDIAL INFARCTION: LESS REPERFUSION THERAPY AND LARGE INFARCT SIZE
Authors: Vincent Roolvink, Saman Rasoul, Jan Paul Ottervanger, Jan-Henk Dambrink, Marcel Gosselink, Jan Hoorntje, Rik Hermanides, Harry Suryapranata, Arnoud Hof, Isala klinieken
Journal: Journal of the American College of Cardiology (2012)
Pseudoarrhythmia Caused by Temporary Transvenous Pacemaker
Authors: Melvyn Rubenfire
Journal: JAMA (1976)

THE INTERPRETATION of arrhythmias on a 12-lead scalar electrocardiogram or on a monitoring strip can frequently be a difficult task. Essential to the interpretation is a good-quality stable baseline without artifacts. We are dependent on proper electrode placement, faultless technical assistance, and quality equipment. Unfortunately, artifacts are not uncommon in full 12-lead scalar ECGs because the equipment must fulfill American Heart Association standards of a wide frequency response range from 0.05 to 100 hertz. With this wide frequency range, the scalar ECG is subject to motion artifacts from respiration, arm movement, muscle tremors such as parkinsonism, and high-frequency electrical signals such as 60-Hz interference. Fortunately, bedside monitors are provided with a low- and high-frequency cutoff that eliminates most artifact. Our patient had a temporary transvenous pacemaker that caused an unusual ventricular pseudoarrhythmia during monitoring. This points out the need for caution in interpretation and treatment of a patient with an