tbuckley/cabot-search huggingface dataset:
Abstract 4768: Investigation of frameshift peptides for cancer vaccines
Authors: Luhui Shen, Jose Cano-Buendia, Hojoon Lee, Chu Bui, Kathryn Sykes, Patricia E. Carrigan, Stephen A. Johnston
Journal: Cancer Research (2010)

Abstract Background: Our overall goal is to develop a general, preventative cancer vaccine. We are systematically applying bioinformatics, proteomics and immunological methods to achieve this vision. One of our foci is the identification of framshifted (FS) neo-peptides in tumor cells as vaccine components. FS peptides are expressed in alternate reading frames which are activated by various gene mutations and abnormal splicings in tumor cells. Aim/Method: Our hypothesis is that FS peptides are recognized as foreign antigens to the immune system thus making them potential cancer vaccine candidates. We have identified a list of FS peptides by bioinformatic analysis using the publically available human tumor and normal EST databases. To set up a systematical approach of prophylactic cancer vaccine development, we evaluated one potential FS peptide on the list as cancer vaccine candidate which is produced by a splice variant in SMC1A (Structural Maintenance of Chromosomes 1A). Results: The SMC1A FS peptide is a 17 amino acid peptide which is encoded by an abnormal alternative splicing event between exon 1 and exon 4. It was detected in mouse tumor cell lines including melanoma (n=2) and a breast tumor cell lines. It was also detected in human tumor cDNAs assayed thus far including breast (n=34), pancreas (n=4), and lung cancer (n=1) cell lines and primary breast (n=7) and pancreatic tumors (n=4). The expression levels of the SMC1 FS variant increases in most primary tumors with ranges from 2 to 70 fold. Specifically we see an increased expression in 6/7 breast and 2/4 pancreatic tumors screened. Single genetic immunization with plasmids expressing SMC1 FS, mouse GM-CSF, and CpG2216 significantly delayed tumor growth in C57BL/6 mice transplanted with the B16F10 melanoma cell line. Both antibody and IFN-γ released splenocytes to SMC1 FS were detected in immunized mice. Discussion: These findings suggest that the SMC1 FS peptide can be a potential cancer vaccine candidate to prevent various tumors. We are applying this same basic approach to accumulate sufficient antigens to constitute a broadly protective, prophylactic cancer vaccine. (This research is supported by an Innovation Award from the DoD and The Keck Foundation to SAJ.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4768.
English Is Our Second Language
Authors: Nicholas P. Christy
Journal: New England Journal of Medicine (1979)

Imagine a medical student, graduated two years ago with a degree in science or the humanities, perhaps with high honors. In his third or core clinical or major medical year, not yet having forgotten all that he learned in college, eager to apply his new "preclinical" erudition to patients, he has just started his clerkship in internal medicine. He goes on rounds. He goes on rounds again. And again. Something is wrong. He understands nothing of what is being said. He understood well enough the scientific material that flooded him in the first two years of medical school, but he . . .
Government Control of Medical Radioisotopes
Authors: Marshall Brucer
Journal: JAMA (1962)

To the Editor:—  On Aug. 26, 1961, federal regulation 49 CFR 197 was published in the Federal Register, Interstate Commerce Commission, Transportation of Explosives and Other Dangerous Articles by Motor Vehicle, (vol. 26, No. 165, page 8040). The regulation states in essence that trucks delivering medical radioisotopes must have 2 attendants and must never stop near a hospital unless continuously attended. The regulation equates any radioactivity—diagnostic and therapeutic—with Class A and Class B explosives. The law states that a 10-μc. capsule of radioiodine might explode, unless guarded, and destroy a hospital.  This may seem like an inconsequential regulation, but it means that the radioactive pharmaceutical manufacturers will have to increase the price of their drugs. It places a ridiculous restriction on the distribution of the drug. It was published in a manner and hidden by a verbiage that for all practical purposes was hidden from the public. None of the
Reduction of False Negative Results in Screening of Newborns for Homocystinuria
Authors: M. Judith Peterschmitt, Jane R. Simmons, Harvey L. Levy
Journal: New England Journal of Medicine (1999)

Mental retardation and other disabilities (including ectopia lentis, osteoporosis, and thromboembolism) in patients who have homocystinuria as a result of a deficiency of cystathionine beta-synthase can be prevented by the screening of newborns with measurement of blood methionine, followed by the early treatment of affected infants. Many infants with this disorder, however, are not identified by screening and have irreversible brain damage.We reviewed the results of neonatal screening for homocystinuria over a period of 32 years in New England. Additional specimens were requested for repeated analysis when blood methionine measurements were at or above the established cutoff level. Homocystinuria due to cystathionine beta-synthase deficiency was confirmed by quantitative amino acid analyses.For the first 23.5 years of the review period, the blood methionine cutoff value was 2 mg per deciliter (134 micromol per liter). Among the 2.2 million infants screened during that period, 8 with homocystinuria were identified (1:275,000). In 1990, the cutoff value was reduced to 1 mg per deciliter (67 micromol per liter). Among the 1.1 million infants screened in the subsequent 8.5 years, 7 with the disorder were identified (1:157,000). During the latter period, the specimens were collected from six of the seven infants when they were two days of age or less; five of the six had blood methionine concentrations below 2 mg per deciliter. Use of the reduced cutoff level increased the false positive rate from 0.006 percent to 0.03 percent.A cutoff level for blood methionine of 1 mg per deciliter in neonatal screening tests for homocystinuria should identify affected infants who have only slightly elevated concentrations of methionine and reduce the frequency of false negative results.
Clinical trials and the acceptance of uncertainty.
Authors: M B Bracken
Journal: BMJ (1987)

Clinical trials and the acceptance of uncertainty Randomised controlled clinical trials continue to be the most scientifically valid method of evaluating the risks and benefits of medical innovations.Writing about randomised clinical trials in the 1%0s, Frederickson called them the "indispensable ordeal."'Few investigators would disagree that they are an ordeal, but questions about their dispensability,2 and even whether they are ethical,' persist.The recent Lugano consensus conference considered the current state of controlled trials and asked whether they are "in crisis."4If there is a crisis it probably stems from doctors' reluctance to accept their uncertainty about much of what they practice.The randomised trial is still misunderstood and underused and is certainly not accepted as an integral part of a professional practice that should constantly strive to improve the efficacy and safety ofits treatments.The Lugano report is useful in highlighting several problems affecting our attitude towards clinical trials.It also suggests why we choose to ignore, or even slay, the bearer of bad news when controlled trials tell us what we do not want to hear about many of our diagnostic and therapeutic manoeuvres.Concern that randomised clinical trials violate the doctor- patient relationship may be the greatest single obstacle to
Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C
Authors: Masao Honda, Mikiko Nakamura, Makoto Tateno, Akito Sakai, Tetsuro Shimakami, Takayoshi Shirasaki, Tatsuya Yamashita, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Shuichi Kaneko
Journal: Journal of Hepatology (2010)
Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors
Authors: Kate F. Whitecross, Amber E. Alsop, Leonie A. Cluse, Adrian Wiegmans, Kellie-Marie Banks, Claudia Coomans, Melissa J. Peart, Andrea Newbold, Ralph K. Lindemann, Ricky W. Johnstone
Journal: Blood (2008)
Community care waiting lists and older people
Authors: J. Young
Journal: BMJ (2001)

The surgical waiting list is a simple summary statistic representing a barometer for the NHS in the United Kingdom. Its rise or fall is an important measure by which politicians and managers gauge the effectiveness of policy and the adequacy of resources. It has a highly visible public profile and is clearly influential in triggering additional resources—as, for example, in sporadic waiting list initiatives. But there is a further fundamental component to health service provision, community care, which is not represented by any simple statistic and is therefore strategically disadvantaged in claiming the public's and politicians' attention.

The surgical waiting list as a performance indicator has been criticised for ascribing equal importance to unequal situations such as cancer and varicose veins. Also it distorts healthcare planning and provision through an excessive and unbalanced focus on elective surgery which directs attention away from acute care services. Nevertheless, the acute services have their own global indicator, which is the number of emergency …
Points: Ethical conflicts
Authors: J Finlayson
Journal: BMJ (1982)

August, p 421), any doctor interested in relieving the dire poverty and hunger in the Third World might be interested in joining the World Development Movement, Bedford Chambers, Covent Gar- den, London WC2E 8HA.This is an organisa- tion which campaigns for a fairer deal for the Third World through activities including lobbying MPs on the implementations of the Brandt Report....
Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.
Authors: D Marples, J Frøkiaer, J Dørup, M A Knepper, S Nielsen
Journal: Journal of Clinical Investigation (1996)

Prolonged hypokalemia causes vasopressin-resistant polyuria. We have recently shown that another cause of severe polyuria, chronic lithium therapy, is associated with decreased aquaporin-2 (AQP2) water channel expression (Marples, D., S. Christensen, E.I. Christensen, P.D. Ottosen, and S. Nielsen, 1995. J. Clin. Invest., 95: 1838-1845). Consequently, we studied the effect in rats of 11 days' potassium deprivation on urine production and AQP2 expression and distribution. Membrane fractions were prepared from one kidney, while the contralateral kidney was perfusion-fixed for immunocytochemistry. Immunoblotting and densitometry revealed a decrease in AQP2 levels to 27+/-3.4% of control levels (n=11, P<0.001) in inner medulla, and 34+/-15% of controls (n=5, P<0.05) in cortex. Urine production increased in parallel, from 11+/-1.4 to 30+/-4.4 ml/day (n=11, P<0.01). After return to a potassium-containing diet both urine output and AQP2 labels normalized within 7 d. Immunocytochemistry confirmed decreased AQP2 labeling in principal cells of both inner medullary and cortical collecting ducts. AQP2 labeling was predominantly associated with the apical plasma membrane and intracellular vesicles. Lithium treatment for 24 d caused a more extensive reduction of AQP2 levels, to 4+/-1% of control levels in the inner medulla and 4+/-2% in cortex, in association with severe polyuria. The similar degree of downregulation in medulla and cortex suggests that interstitial tonicity is not the major factor in the regulation of AQP2 expression. Consistent with this furosemide treatment did not alter AQP2 levels. In summary,hypokalemia, like lithium treatment, results in a decrease in AQP2 expression in rat collecting ducts, in parallel with the development of polyuria, and the degree of downregulation is consistent with the level of polyuria induced, supporting the view that there is a causative link.
Neutropenia, Inflammation, and the Kinetics of Transfused Neutrophils in Rabbits
Authors: Marc S. Rosenshein, Thomas H. Price, David C. Dale
Journal: Journal of Clinical Investigation (1979)

A rabbit model was used to study the effects of neutropenia and inflammation on the intravascular distribution, survival, and tissue accumulation of transfused neutrophils. Donor blood labeled with [3H]thymidine was infused into normal or neutropenic (vinblastine treated) animals. Inflammation was created by subcutaneous implantation of polyvinyl sponges, some with added endotoxin. Initial circulating neutrophil pool recovery, survival, and inflammatory site accumulation of labeled neutrophils were measured.
THE ETHICS OF THE MEDICAL PROFESSION.
Authors: DUDLEY S. REYNOLDS
Journal: JAMA (1895)

Ethics is the written code of rules of right conduct for societies, professions, and all bodies of people having a common interest in the advancement of themselves in their individual relations to each other, and of the growth and advancement of the class to which they belong. Politics has for its main object the betterment of the forms of government; and political societies, professions and systems grow in importance as nations or states are made up of people willing to mold their personal conduct to a harmonious general standard in respect to each other's rights as defined by law. Ethics must be construed to mean the right conduct of people toward each other in their associate relations; and so the ethics of a professional class must define the right conduct of individual members of that class, in the growth and advancement of the whole body. The ethics of the medical
Injectable thermosensitive PEG–PCL–PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects
Authors: PeiYan Ni, QiuXia Ding, Min Fan, JinFeng Liao, ZhiYong Qian, JingCong Luo, XiuQun Li, Feng Luo, ZhiMing Yang, YuQuan Wei
Journal: Biomaterials (2013)
Clorazepate Dipotassium in the Treatment of Intractable Epilepsy
Authors: Harold E. Booker
Journal: JAMA (1974)

Clorazepate dipotassium was given to 59 patients whose epileptic seizures were intractable to treatment with standard antiepileptic drugs. On absorption, clorazepate dipotassium is rapidly decarboxylated to yield<i>N</i>-desmethyl diazepam, a normally occurring metabolite of diazepam. Excellent results were obtained in 20 patients, principally those with generalized minor attacks. Six of these had previously failed to respond to diazepam. No benefit was seen in 14 patients with typical psychomotor attacks. The results suggest that clorazepate dipotassium is a useful addition to the treatment of intractable minor seizures. (<i>JAMA</i>229:552-555, 1974)
Is atopy a protective or a risk factor for cancer? A review of epidemiological studies
Authors: H. Wang, T. L. Diepgen
Journal: Allergy (2005)

Objective: There is an ongoing debate whether there is a link between a history of atopy and cancer risk. The purpose of this paper is to review the published epidemiological studies on the association between atopy and the risk of cancers. Methods: Through an electronic search (January 1986–April 2004) with an additional review of cited references, we identified studies with quantitative data on the relation of atopy (irrespective of its definition or subtype) to cancer (different cancer sites). Results: The protective effect of atopy in colorectal cancer has been observed consistently in the case–control studies, but not in cohort studies. A consistent inverse association between self‐reported atopy and glioma risk has been shown, but there is absence of such an association for meningioma. In most studies, the risk of leukaemia, in particular childhood leukaemia, tends to be lower among people with a history of atopy. Studies, which looked at, the association between atopic diseases and risk of cancers of pancreatic, breast, lymphoma showed varying outcomes. Most studies on the atopy–pancreatic cancer relation suggested an inverse association. For lymphoma, most studies have shown no substantial association. Overall evidence indicates an increased risk of lung cancer among persons with a history of asthma. Conclusion: Despite the mixed results, the emerging picture from most of the currently available epidemiological data indicate that atopic disease is associated with a reduced risk for cancer. Further research should focus on a more carefully defined ‘atopy’ status and manifestation of different atopic diseases, to advance our understanding of the role that allergies might play in the risk of developing cancer.
Possible cause of false normal B-12 assays
Authors: Malcolm S Hamilton, Sheena Blackmore, Anne Lee
Journal: BMJ (2006)

Editor-Last year Hern et al published an editorial on knife crime and clearly the problem has not gone away. 1 A quick search of the Times website finds 90 hits on the single search term "stabbing" in the past three months alone.Several recent deaths have fuelled the perception that forensic knife injuries have become an epidemic, resulting in a knife amnesty and government discussion of new punitive measures.An increase in such injuries is supported by data from regional police forces and the Home Office, with 1200 reported attacks in London last year and 30% of homicides caused by knife injury. 2 Crimes defined as "more serious wounding or other act endangering life" almost doubled nationally from 1995 to 2005. 3 We audited forensic knife injuries at this hospital, one of Europe's busiest emergency departments, to establish the size of this problem in a representative urban area (east London).We extracted data on forensic knife injuries (excluding deliberate self harm) from a detailed prospectively recorded database of all trauma calls from July 2004 to June 2006 (these reflecting more severe injuries).Overall there were 309 forensic knife injuries; 259 patients were admitted, 184 were operated on, and eight died.The chest was the most common area injured (183/309 patients, 6/8 deaths).Most patients were men (297/309), and mean age was 28 (range 15-74).To give a measure of changing incidence over a longer time of a greater range of severity of injury, we also performed an audit of all cases coded as "stabbing" on the patient administration system during the 10 year period from July 1997 to June 2006 (figure).Over both periods, the data show an increase in the overall incidence of stabbings.Furthermore, increased need for surgical intervention in the prospective study may reflect increasing severity of injury.These data therefore seem to support the general perception that knife injuries are increasing.
Abstract B101: NFAT regulates a gene expression program associated with invasiveness and poor prognosis in colorectal cancer
Authors: Manish K. Tripathi, Shinji Mima, Zhiao Shi, Naresh Prodduturi, Zhu Jing, Kristen K. Ciombor, Xi Chen, Natasha Deane, Robert D. Beauchamp, Bing Zhang
Journal: Cancer Research (2013)

Abstract Colorectal cancer is the second leading cause of cancer-related death in the United States. In order to understand the regulatory mechanisms underlying poor prognosis in colorectal cancer, we analyzed fourteen human colorectal cancer microarray data sets and identified co-expressed modules using network analysis. We next filtered these modules using gene expression data from a mouse model of metastatic colon cancer, narrowing down to a candidate metastasis-related module, and identified NFAT as its potential transcriptional regulator. The NFAT family and their identified targets were found to be upregulated in human colorectal cancer patients. Analysis of NFAT family members expression in mouse and human microarray datasets, revealed NFATc1 to be differentially expressed between metastatic and non-metastatic, and between disease progression and no disease progression, respectively. We found that high NFATc1 expression correlated with significantly increased invasion (p&amp;lt;0.0001) and migration (p&amp;lt;0.005) in mouse colon cancer cells. We show that RNAi- based knockdown of NFATc1 and functional inhibition by the calcineurin inhibitor FK506 resulted in downregulation of predicted NFAT target genes from the metastatic module and decreased cancer cell invasiveness. Finally, we showed that the expression of NFAT target genes was significantly correlated with both disease-specific and disease-free survival in Stage II and III colorectal cancer patients. Our studies suggest a role for NFATs in colon cancer cell invasion and a potential application for the NFAT driven program as a biologically anchored prognostic gene expression signature. Citation Format: Manish K. Tripathi, Shinji Mima, Zhiao Shi, Naresh Prodduturi, Zhu Jing, Kristen K. Ciombor, Xi Chen, Natasha Deane, Robert D. Beauchamp, Bing Zhang. NFAT regulates a gene expression program associated with invasiveness and poor prognosis in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B101.
Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study
Authors: Lucien Noens, Marie-Anne van Lierde, Robrecht De Bock, Gregor Verhoef, Pierre Zachée, Zwi Berneman, Philippe Martiat, Philippe Mineur, Koen Van Eygen, Karen MacDonald, Sabina De Geest, Tara Albrecht, Ivo Abraham
Journal: Blood (2009)
INCREASED SUSCEPTIBILITY OF MICE INFECTED WITH MOUSE ADENOVIRUS TO ESCHERICHIA COLI-INDUCED PYELONEPHRITIS
Authors: David R. Ginder
Journal: The Journal of Experimental Medicine (1964)

Mouse adenovirus causes a persistent infection in the mouse kidney that produces extensive mononuclear cell infiltrates in cortex and medulla. Tubular necrosis, dilatation, and occasional collapse occur but no glomerular changes or periglomerular fibrosis have been observed. Acute and chronic adenovirus infection of the kidney predispose the kidney to develop acute pyelonephritis when the mouse is challenged by the intravenous or retrograde route with Escherichia coli.