tbuckley/cabot-search huggingface dataset:
OS09.4 Identification of a novel H3.3.K27M mutation-derived neoantigen epitope and cloning of H3.3.K27M-specific T-cell receptor for T-cell therapy in gliomas
Authors: Z. Chheda, G. Kohanbash, J. Sidney, K. Okada, N. Jahan, S. Mueller, A. Sette, Y. Hou, H. Okada
Journal: Neuro-Oncology (2017)

Brain cancers are the leading cause of cancer related mortality and morbidity in children and young adults. Children with diffuse intrinsic brainstem malignant gliomas have one-year progression-free survival rates below 25% and median overall survival of 9 to 10 months with current treatment options and hence represent a significant unmet medical need. Genome-wide sequencing efforts of pediatric gliomas have identified a recurrent and shared missense mutation in the gene encoding the replication-independent variant of histone 3, H3.3. Approximately 70% of diffuse intrinsic pontine gliomas (DIPG) and 50% of thalamic and other midline gliomas harbor the amino-acid substitution from lysine (K) to methionine (M) at the position 27 of H3.3 gene (H3.3.K27M mutation). Tumor-specific missense mutations are not subjected to self-tolerance and can be suitable targets (i.e. neoantigen) for cancer immunotherapy. We evaluated whether the H3.3.K27M mutation can induce specific cytotoxic T lymphocyte (CTL) response in HLA-A2+ human T cells. In vitro stimulation of HLA-A2+ donor-derived CD8+ T-cells with a synthetic peptide encompassing the H3.3.K27M mutation (H3.3.K27M epitope) induced CTL lines which recognized not only T2 cells loaded with the synthetic H3.3.K27M epitope peptide but also lysed HLA-A2+ DIPG cell lines which endogenously harbor the H3.3.K27M mutation. On the other hand, the CTL lines did not react to either HLA-A2+ H3.3.K27M -negative DIPG cell lines or H3.3K27M-positive but HLA-A2-negative cells. The H3.3.K27M epitope peptide, but not the non-mutant counterpart, indicated an excellent affinity (Kd 151nM) to HLA-A2 based on competitive binding inhibition assay. From CTL clones with high and specific affinities to HLA-A2-H3.3.K27M-tetramer, cDNAs for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector. Human HLA-A2+ T-cells transduced with the TCR demonstrated antigen-specific reactivity as well as anti-glioma responses in vitro. Peptide titration assay suggested that the H3.3.K27M-specific TCR had the half-maximal reactivity for peptide recognition of around 100nM. Furthermore, critically important for safety of clinical application, alanine scanning demonstrated that the key amino-acid sequence motif in the epitope for the TCR reactivity is not shared by any known human protein. Finally, intravenous administration of T-cells transduced with the H3.3.K27M-specific TCR significantly inhibited the growth of intracranial HLA-A2+ H3.3.K27M-positive glioma xenografts in immune-deficient mice. These data provide us with a strong basis for developing peptide-based vaccines as well as adoptive transfer therapy using autologous T-cells transduced with the H3.3.K27M-specific TCR.
Orexins in the Brain-Gut Axis
Authors: A. L. Kirchgessner
Journal: Endocrine Reviews (2002)

Orexins (hypocretins) are a novel pair of neuropeptides implicated in the regulation of energy balances and arousal. Previous reports have indicated that orexins are produced only in the lateral hypothalamic area, although orexin-containing nerve fibers were observed throughout the neuroaxis. Recent evidence shows that orexins and functional orexin receptors are found in the periphery. Vagal and spinal primary afferent neurons, enteric neurons, and endocrine cells in both the gut and pancreas display orexin- and orexin receptor-like immunoreactivity. Orexins excite secretomotor neurons in the guinea pig gut and modulate gastric and intestinal motility and secretion. In addition, orexins modulate hormone release from pancreatic endocrine cells. Moreover, fasting up-regulates the phosphorylated form of cAMP response element binding protein in orexin-immunoreactive enteric neurons, indicating a functional response to food status in these cells. The purpose of this article is to summarize evidence for the existence of a brain-gut network of orexin-containing cells that appears to play a role in the acute regulation of energy homeostasis.
Precision Over Convenience
Journal: JAMA (1972)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
P53 protein immunoreactivity in extrahepatic bile duct and gallbladder cancer: Correlation with tumor grade and survival
Authors: I DIAMANTIS
Journal: Hepatology (1995)

Forty-five extrahepatic bile duct carcinomas (i.e., tumors of the region proximal to the duct junction, including Klatskin tumors, tumors of the lower mid-region, and tumors of the ampulla of Vater) and 11 gallbladder carcinomas were immunohistochemically examined for p53 protein expression, using the DO-7 monoclonal (mAb) and the CM-1 polyvalent (pAb) antibodies and an antigen retrieval method. Because the DO-7 mAb was found to be significantly more reliable than the CM-1 pAb in detecting p53 immunoreactivity, the immunohistochemical results obtained with the former antibody were used for comparing p53 protein immunoreactivity with tumor site, tumor grade, and survival of patients. Approximately one third (3 of 10) of the proximal tumors were found to express weak p53 immunopositivity, whereas moderate immunopositivity and higher rate (18 of 29) was observed in tumors of the lower mid-region. Finally, moderate and marked p53 immunopositivity was observed in tumors of the ampulla (5 of 6) and gallbladder (8 of 11). In tumors of the lower mid-region of the ampulla and the gallbladder, a significantly higher p53 positivity was noted in high-grade compared with lowgrade neoplasms. For the cases in which complete follow-up was available (11 tumors of the low mid-region), median survival of patients with p53-negative tumors was 25.7 months, whereas survival of those with p53-positive tumors was 5.2 months. In conclusion, our findings suggest that (1) p53 protein is differentially expressed in extrahepatic bile duct carcinomas, thus stressing the clinical and histological distinction between proximal and lower duct tumors, (2) in a subset of the above carcinomas, p53 protein expression appears to be related to higher grades of malignancy, and (3) the presence of p53 immunopositivity might be associated with a shorter survival of the patients. (Hepatology 1995; 22:774–779.)
THE EATING OF ICES.
Journal: JAMA (1896)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Lung Cancer Screening Recommended for Heavy Smokers
Journal: Cancer Discovery (2014)

New guidelines from the U.S. Preventive Services Task Force recommend that smokers between the ages of 55 and 80 who have smoked for at least 30 pack-years, or former smokers who meet the age and pack-year criteria but quit less than 15 years ago, undergo annual screenings for lung cancer using low-dose computed tomography.
Symptom association in ambulatory gastro-oesophageal reflux monitoring: a systematic analysis
Authors: M. R. Fox, R. Sweis, A. Anggiansah, T. Wong, D. Menne
Journal: Gut (2011)

<h3>Introduction</h3> The diagnosis of gastro-oesophageal reflux disease (GORD) by ambulatory reflux monitoring is based on oesophageal acid exposure time (AET) or temporal association of reflux events with patient symptoms. Several key issues required for reflux-symptom association, such as the most appropriate pH threshold and time window, have not been defined and current statistical analysis has important limitations: Symptom Index (SI) is a measure of an effect size, not of confidence. Symptom Association Probability (SAP) is a measure of confidence but not of size and applies the Fisher exact test inappropriately (dividing time into fixed intervals does not produce independent counts). This study presents a systematic assessment of symptom association in ambulatory gastro-oesophageal reflux monitoring data. <h3>Methods</h3> Acid reflux (pH) and symptom data were acquired by wireless pH recording (Bravo, Given Imaging). 163 consecutive patients presenting with predominantly typical reflux symptoms (heartburn, regurgitation) studied 2006–2009 with duration &gt;3.7 days were studied (636 days). Data were exported in XML format, and analyzed by custom written program. A systematic analysis was performed. <h3>Results</h3> (1) Symptom markers A finite-state algorithm was developed to equalise patient responses, removing redundant markers in one pass with reflux detection. (2) pH threshold: Setting pH thresholds for reflux detection is not physiological and a weighted S-shaped (‘dose response9) curve could be more appropriate. This was assessed varying the centre and steepness of the curve to maximise association with SI and SAP. A steep S-curve almost indistinguishable to a threshold was found: maximum correlation SI pH threshold 4.5, correlation 0.55; SAP pH threshold 4.4, correlation 0.34. (3) time window: The frequency of reflux associated symptom markers was above baseline only during minute 1. The association in minute 2 was no higher than chance. (4) Over time (day 1–4) SI was stable; however SAP increased progressively. Both parameters increased with the frequency of reflux events. CI for SI were computed by assuming a binomial distribution (Agresti-Coull method). <h3>Conclusion</h3> A novel approach to symptom association of ambulatory reflux monitoring data is presented. Confounding due to redundant symptom markers is removed by a finite-state algorithm. Acid threshold of pH 4.5 and a time window of 1 min provided optimal correlation with SI. Computing SI with CI provides a statistically valid, single parameter that describes both size of effect and likelihood of association between reflux events and symptoms.
MEDICAL DEFENSE IN DETROIT.
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
B-type natriuretic peptide (BNP) predicts future cardiac events in patients presenting to the emergency department with dyspnea Alex T. Harrison, Padma Krishnaswamy, Radmila Kazanegra, Quyen Dao, Alan Maisel. San Diego VA Health Care System, San Diego, CA, University of California San Diego (UCSD), San Diego, CA
Journal: Journal of the American College of Cardiology (2001)
A Prospective Study of Vitamin E and Coronary Heart Disease Among Men:
Authors: Eric B Rimm
Journal: Circulation (2001)

0016 A growing body of evidence suggests that oxidative modification of LDL-cholesterol is important in the early development of atherosclerotic lesions. Although past observational epidemiologic evidence suggests CHD benefit for long term vitamin E supplement use, two recent large secondary prevention trials have not found a lower risk of CVD among patients randomized to vitamin E. Data comparing the benefits of vitmain E between populations with and without prior CVD have not been adequately explored. We examined prospectively the association between vitamin E supplements (&gt;100 IU/day for 2 or more years) and risk of coronary heart disease among 38,884 U.S. male health professionals, 40 to 75 years of age at baseline (1986) and who were free of diagnosed CVD, diabetes, and cancer. During ten years of follow-up, we documented 1145 incident cases of fatal and non-fatal myocardial infarction (MI). After controlling for several known coronary risk factors, we observed a lower risk of coronary disease among men with use of vitamin E supplements. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of MI of 0.78 (95 percent confidence interval, 0.65 to 0.95). The benefits of vitamin E were substantially greater among populations free of CVD-related conditions. Among men without self-reported physician-diagnosed hypercholesterolmia, the RR of MI for vitamin E was 0.74 (95% CI 0.60,0.93). Men with hypercholesterolemia did not show appreciable benefit from vitamin E (RR=0.93;95% CI 0.63, 1.37). Men without hypertension had a lower risk of MI associated with vitamin E use (RR=0.74;95% CI 0.58, 0.94) than men with hypertension (RR=0.88;95% CI0.63, 1.22). Men free of either condition showed a significantly greater benefit from taking vitamin E (RR=0.71; 95% CI 0.54, 0.92) than men with either of these two conditions (RR=0.88; 0.67, 1.17). These data suggest a reduced risk of CHD for long term vitamin E supplement use among an otherwise healthy population and are consistent with the recent null findings from secondary prevention trials.
Pathological and Practical Researches on the Various Forms of Paralysis
Authors: E. Meryon
Journal: BMJ (1863)

larger number of cells.At this period, the skin sur- rounding the vesicle had begun to redden; and the vesicle was no longer transparent, but opaline.On the tenth day, the redness of the skin around the vesicle lhadl increased.The vesicle itself was full of a rnilky flnid: this, uipon examination, appeared to con- tain numerouis pus-cells.Dr. )Marston fouind, however, that if a vaccine vesicle be irritated, the surrounding skin will become red on the eiglitl-h day.The contents of the vesicle will at the same time become opaline or Yellowish; and, if examined microscopically at this period, will contain cells having the appearance cf pus.These observations lave ni.ow been sufficiently mtulti- plied to warrant the following conclulsions:-1.The ordinary vaccine vesicle yields a fluid, from the fifth to the eighth (Idy, free from any cells allied to on 24 July
Acute hemolytic anemia complicating infectious mononucleosis
Authors: A. M. Fekete
Journal: JAMA (1965)

INFECTIOUS mononucleosis is a frequent cause for hospitalization. The usual clinical course of the disease is one of gradual and uneventful recovery. The entity can have such protean manifestations, however, that in the absence of the more classical findings, it may not be suspected. Though unusual, an acute hemolytic anemia can complicate the picture.<sup>10</sup>Such a situation can present a very serious medical problem. While approximately only 30 cases have been reported in the American literature, it is conceivable that more would be found if sought for (James, G.W., personal communication, June 6, 1964). In a thorough review of the records at the two major local hospitals, only three cases of this entity were noted in the past five years. The case presented here is one of an infectious mononucleosis complicated by a severe hemolysis which was considered attributable to an autoimmune mechanism. <h3>Report of a Case</h3> A 22-year-old white
CRISPR Meets CAR T-cell Therapy
Journal: Cancer Discovery (2017)

Using CRISPR/Cas9 technology, researchers have devised a method to deliver a CAR gene to a specific locus, TRAC, in T cells. This targeted approach yielded therapeutic cells that were more potent even at low doses; in a mouse model of acute lymphoblastic leukemia, they outperformed CAR T cells created with a randomly integrating retroviral vector.
Equine Virus: A Possible Future Pathogen in Man
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Medics' War: what happened at Chipyong-ni
Authors: R. M. Hall
Journal: JAMA (1991)

<h3>In Reply. —</h3> Dr Hall's charge of physician bashing will be recognized as absurd by all readers of<i>The Medics' War</i>, whether they are physicians or laypersons. The theme of the book is that the army's need to attract physicians in the aftermath of World War II led the service to emphasize clinical training and specialization and, at the same time, to neglect field training for its medical officers. The result was a service of superb professional competence combined, sometimes tragically, with a lack of military knowledge and experience among the junior officers. On the very page denounced by Dr Hall, I say: "Though casualties exceeded all predictions, hospital death rates were the lowest in the history of warfare. At a time when the draft had not yet come to solve the problem of procuring doctors, this accomplishment belonged to the Medical Service almost alone, to its cadre of experienced
Errors in Abstract and Figures 2 and 3
Authors: Steven Frucht, Michael Aminoff
Journal: JAMA Neurology (2018)

Xia Wang, PhD; Thompson G. Robinson, MD; Tsong-Hai Lee, MD; Qiang Li, MBiostat; Hisatomi Arima, MD, PhD; Philip M. Bath, FRCP, DSc; Laurent Billot, MSc; Joseph Broderick, MD; Andrew M. Demchuk, MD; Geoffrey Donnan, MD; Jong S. Kim, MD, PhD; Pablo Lavados, MD; Richard I. Lindley, MD; Sheila O. Martins, MD; Veronica V. Olavarria, MD; Jeyaraj D. Pandian, MD, DM; Mark W. Parsons, MD, PhD; Octavio M. Pontes-Neto, MD; Stefano Ricci, MD; Vijay K. Sharma, MD; Nguyen H. Thang, MD; Ji-Guang Wang, MD, PhD; Mark Woodward, PhD; Craig S. Anderson, MD, PhD; John Chalmers, MD, PhD; for the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) Investigators
Pseudo-Sylvian aqueduct syndrome
Authors: M. P. Cruciger
Journal: JAMA (1981)

<h3>To the Editor.—</h3> In response to a physician's inquiry about the spontaneous development of localized poliosis (whitening of the hair), the consultant (1981:246;284) cites several common causes, including radiation therapy, alopecia areata, severe dermatitis, and vitiligo. Two additional possibilities are described in ancient Hebrew writings. The Babylonian Talmud (Tractate Berachoth folios 27b and 28a) relates that when the wise and sagacious Rabbi Eleazar ben Azariah was asked whether or not he would consent to become head of the rabbinical academy, his wife said to him: "You have no white hair." He was 18 years old on that day, and a miracle was wrought for him as 18 rows of hair on his beard turned white. That is why he said: "Behold, I am like seventy years old" and did not simply say seventy years old. The commentator Rabbi Shlomo ben Yitzchok, popularly known as Rashi, states that Rabbi Eleazar ben
Just Words
Authors: Stanley S. Schor
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal