tbuckley/cabot-search huggingface dataset:
Targeting immune checkpoint pathways overcomes tumor-induced CD8+ T cell suppression
Authors: Lukas W Pfannenstiel, Brian R Gastman
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The immune system has the potential to be a powerful tool to destroy tumors. However despite ample evidence of anti-tumor immune responses in many patients, as well as years of immunotherapy development, truly effective immune-based therapies remain out of reach. We have
Cetuximab-Related Tumor Lysis Syndrome in Metastatic Colon Carcinoma
Authors: Ganapathy Krishnan, Karl D'Silva, Anas Al-Janadi
Journal: Journal of Clinical Oncology (2008)

an approximate half-life of 24 to 48 hours, there may have been residual sorafenib present during radiation treatment and thus normal tissue was still radiosensitized via sorafenib.This report describes a patient receiving sorafenib that developed a lumbar metastasis that required irradiation.She died of complications in the bowel-the area directly targeted by irradiation.In conclusion, this case provides evidence for potential oversensitization of normal tissue by sorafenib.Further studies combining antiangiogenic therapy with radiotherapy are warranted in order to further determine the efficacy and toxicity of combination therapy of sorafenib with radiation.
γ-Secretase Inhibitor Reduces Allergic Pulmonary Inflammation by Modulating Th1 and Th2 Responses
Authors: Jin Hyun Kang, Byung Soo Kim, Tae Gi Uhm, Shin-Hwa Lee, Gap Ryol Lee, Choon-Sik Park, Il Yup Chung
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Gamma-secretase inhibitor (GSI) has been used to effectively block Notch signaling, which is implicated in the differentiation and functional regulation of T helper (Th) effector cells. In asthma, a subset of CD4(+) T cells is believed to initiate and perpetuate the disease.The aim of this study was to evaluate the therapeutic potential of GSI against allergic asthma.GSI was administered to an ovalbumin-sensitized mouse via an intranasal route at the time of ovalbumin challenge.The administration of GSI inhibits asthma phenotypes, including eosinophilic airway inflammation, goblet cell metaplasia, methacholine-induced airway hyperresponsiveness, and serum IgE production. GSI treatment of bronchoalveolar lavage cells stimulated via TCR or non-TCR pathways led to a decrease in Th2 cytokine production with a concomitant increase in Th1 cytokine secretion. Expression of Hes-1, a target of Notch signaling, was down-regulated in conjunction with a reduction of Notch intracellular domain and GATA-3 levels after GSI treatment of bronchoalveolar lavage cells. GSI treatment resulted in an inhibition of NF-kappaB activation, and combined treatment with GSI and an NF-kappaB inhibitor augmented IFN-gamma production in a synergistic manner.These data suggest that GSI directly regulates Th1 and Th2 responses in allergic pulmonary inflammation through a Notch signaling-dependent pathway and that GSI is of high therapeutic value for treating asthma by inhibiting airway inflammatory responses.
Bureau of Public Health.
Authors: S. M. Cullom
Journal: JAMA (1898)

United States Senate, Washington, D. C., Dec. 23, 1897.  To the Editor:  —Your favor of the 16th inst. has been received and read with interest. I note what you say with reference to the united effort on the part of the medical profession of our State, supported by the medical men throughout the country, in favor of the establishment of an independent bureau with a commissioner to be appointed by the President at its head.  There is no class of professional men in this or any other country more entitled to the highest consideration than that of the medical profession. Upon that profession the people always rely in times of physical distress in their everyday life, or in times when contagious diseases seize and threaten the lives of the people of a locality and the communities surrounding it, among whom the malady is likely to be spread.  I therefore should
An Outbreak of Smallpox in American Military Personnel in Japan
Authors: Horst A. Agerty
Journal: New England Journal of Medicine (1947)

SMALLPOX, an ancient disease whose prevention has been so readily achieved since the days of Jenner, continues to manifest itself. Even in some parts of the United States the record is shameful. A number of states, especially in the West and Northwest, do not have compulsory vaccination laws. In 1924 Minneapolis had 860 cases, with 219 deaths. In 1931 a total of 30,232 cases were reported from the country as a whole. More recently, however, the morbidity figures have markedly declined, there having been reported only 346 cases in this country in 1945.Most physicians have never seen a case . . .
Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi-centre randomized double-blind study
Authors: S.S. BLEEHEN, S.E. THOMAS, M.W. GREAVES, JULIA NEWTON, C.T.C. KENNEDY, F. HINDLEY, R. MARKS, M. HAZELL, N.R. ROWELL, G.M. FAIRISS, P.H. CARTWRIGHT, H.P. GLENNY, K. HOWLAND
Journal: British Journal of Dermatology (1987)

Journal Article Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi‐centre randomized double‐blind study Get access S.S. BLEEHEN, S.S. BLEEHEN Royal Hallamshire Hospital, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.E. THOMAS, S.E. THOMAS Royal Hallamshire Hospital, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.W. GREAVES, M.W. GREAVES Institute of Dermatology, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar JULIA NEWTON, JULIA NEWTON Institute of Dermatology, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.T.C. KENNEDY, C.T.C. KENNEDY Royal Intirmary, Bristol, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar F. HINDLEY, F. HINDLEY Royal Intirmary, Bristol, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. MARKS, R. MARKS Welsh National School of Medicine, Cardiff, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. HAZELL, M. HAZELL Welsh National School of Medicine, Cardiff, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar N.R. ROWELL, N.R. ROWELL General Infirmary, Leeds Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.M. FAIRISS, G.M. FAIRISS General Infirmary, Leeds Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar ... Show more P.H. CARTWRIGHT, P.H. CARTWRIGHT General Infirmary, Leeds Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar H.P. GLENNY, H.P. GLENNY Smith Kline and French Research, Welwyn, Hertfordshire, U.K. Dr H.P.Glenny, Department of Clinical Research and Development, Smith Kline and French Research, The Frythe, Welwyn, Hertfordshire AL6 9AR, U.K. Search for other works by this author on: Oxford Academic Google Scholar K. HOWLAND K. HOWLAND Smith Kline and French Research, Welwyn, Hertfordshire, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 1, 1 July 1987, Pages 81–88, https://doi.org/10.1111/j.1365-2133.1987.tb04095.x Published: 01 July 1987
HYSTERECTOMY BY THE PRATT METHOD—THE SURGICAL ASPECTS OF HYDROCEPHALUS.—AN OBSCURE CASE OF HEMATURIA—OPERATION FOR STRICTURE OF THE RECTUM.
Authors: EMORY LANPHEAR
Journal: JAMA (1894)

Mrs. B., a patient of Dr. R. A. Brogan, Osage Mission, Kan., who has been sent to the Hospital for operative treatment. She is 54 years of age, married at the age of 20, never pregnant, always in good health, but naturally thin. At about the age of 47 she ceased menstruating and passed through the climacteric without difficulty. Some two or three years subsequently she noticed a slight heaviness in the pelvis, and consulted her physician, who told her that she had some form of tumor growing in the womb. A little more than four years ago she began to have hemorrhages at irregular intervals. These attacks of bleeding have increased in frequency and intensity, until, as you see, she is exsanguinated and almost a skeleton. Examination of the case upon her admission to the Hospital showed that she had an intramural growth which was undergoing decomposition, and that
Identification and characterization of a gene regulating enzymatic glycosylation which is induced by diabetes and hyperglycemia specifically in rat cardiac tissue.
Authors: Y Nishio, C E Warren, J A Buczek-Thomas, J Rulfs, D Koya, L P Aiello, E P Feener, T B Miller, J W Dennis, G L King
Journal: Journal of Clinical Investigation (1995)

Primary cardiac abnormalities have been frequently reported in patients with diabetes probably due to metabolic consequences of the disease. Approximately 2,000 mRNA species from the heart of streptozotocin-induced diabetic and control rats were compared by the mRNA differential display method, two of eight candidate clones thus isolated (DH1 and 13) were confirmed by Northern blot analysis. The expression of clone 13 was increased in the heart by 3.5-fold (P < 0.05) and decreased in the aorta by twofold (P < 0.05) in diabetes as compared to control. Sequence analysis showed that clone 13 is a rat mitochondrial gene. DH1 was predominantly expressed in the heart with an expression level 6.8-fold higher in the diabetic rats than in control (P < 0.001). Insulin treatment significantly (P < 0.001) normalized the expression of DH1 in the hearts of diabetic rats. DH1 expression was observed in cultured rat cardiomyocytes, but not in aortic smooth muscle cells or in cardiac derived fibroblasts. The expression in cardiomyocytes was regulated by insulin and glucose concentration of culture media. The full length cDNA of DH1 had a single open-reading frame with 85 and 92% amino acid identity to human and mouse UDP-GlcNAc:Gal beta 1-3GalNAc alpha R beta 1-6 N-acetylglucosaminyltransferase (core 2 GlcNAc-T), respectively, a key enzyme determining the structure of O-linked glycosylation. Transient transfection of DH1 cDNA into Cos7 cells conferred core 2 GlcNAc-T enzyme activity. In vivo, core 2 GlcNAc-T activity was increased by 82% (P < 0.05) in diabetic hearts vs controls, while the enzymes GlcNAc-TI and GlcNAc-TV responsible for N-linked glycosylation were unchanged. These results suggest that core 2 GlcNAc-T is specifically induced in the heart by diabetes or hyperglycemia. The induction of this enzyme may be responsible for the increase in the deposition of glycoconjugates and the abnormal functions found in the hearts of diabetic rats.
Orthopedic Pathophysiology In Diagnosis and Treatment
Authors: Irwin M. Siegel
Journal: JAMA (1990)

<i>Orthopedic Pathophysiology in Diagnosis and Treatment</i>is a book that was waiting to be written, and I am pleased to see it finally in print. This much-needed survey of "The Principal Musculoskeletal Lesions Encountered in Practice," which emphasizes "those pathological and pathophysiological features important to the clinician, that is, the features important for diagnosis and treatment," is authored by Jonathan Cohen, Michael Bonfiglio, and Crawford J. Campbell. These three are heavy cannons and eminently qualified for this task. What they've given us is a text that discusses and integrates basic pathology with clinical findings, laying a basis for rational and informed therapeutic decision making. Not every orthopedic problem needs to be covered as the emphasis is on method and process rather than material and technique. Each section is well focused. There is a cogent introductory chapter on interpretive skills, after which we plunge headlong into one on inflammation and infection.
SHORT TERM INCREASE IN FREE FATTY ACIDS AND INTRACELLULAR MYOCARDIAL LIPID CONTENT DOES NOT DEPRESS LEFT VENTRICULAR PERFORMANCE IN HEART FAILURE PATIENTS WITH TYPE 2 DIABETES
Authors: Roni R. Nielsen, Helene N&oslash;rrelund, Ulla Kampmann, Yong Kim, Steffen Ringgaard, Michael Sch&auml;r, Hans Erik B&oslash;tker, henrik wiggers
Journal: Journal of the American College of Cardiology (2012)
"A Wisconsin Diploma Mill."
Authors: U. O. B. Wingate
Journal: JAMA (1896)

Milwaukee, Wis., April 27, 1896. <h3>To the Editor:</h3> —I would like to reply to Emil Bories, M.D., whose interesting communication appeared in your issue of April 25. Section 1771 of the General Statutes of Wisconsin, as amended by chapter 220, laws of 1883, and chapters 180 and 352, laws of 1887, provide that, "Three or more adult persons, residents of the State, may form a corporation in a manner provided in this chapter to conduct, or pursue, or promote any one or more of the following named purposes." Among many things it provides for obtaining a charter, which is to be issued by the Secretary of State, for "establishing and maintaining schools, high schools, academies, seminaries, colleges, universities, lyceums and the like." Also for the "Establishment and maintenance of any benevolent, charitable or medical institution, hospital or asylum, etc." Under the provisions of this statute, the founders of the "Wisconsin
High-Frequency Endoscopic Ultrasonography in the Evaluation of Superficial Esophageal Cancer
Authors: Y. Murata, B. Napoleon, S. Odegaard
Journal: Endoscopy (2003)

Recently, there has been an increase in the detection of superficial esophageal cancer, and the 5-year survival rate in patients with m-type mucosal cancer is much higher than that of patients with sm-type cancer invading the submucosa. Since the frequency of lymph node metastasis with m-type tumors is lower than with sm cancers, endoscopic treatment such as endoscopic mucosal resection (EMR) has been carried out in patients with the former type. The Japanese Society of Esophageal Diseases carried out a survey of the histopathological results in 2418 cases of untreated superficial esophageal cancers resected by operation or EMR in 143 hospitals during 1990 - 1994 [1]. EMR was carried out in 394 patients, while the other patients underwent conventional surgery. The depth of cancer invasion was classified according to six categories: cancer limited to the epithelium was described as m1; cancer limited to the lamina propria was m2; invasion reaching the muscularis mucosa or invading the muscularis mucosa was m3; invasion of the submucosa to less than 200 µm was sm1; that reaching the proper muscle was classed as sm3; and invasion between sm1 and sm3 was sm2 (Figure [1]). The rates of lymph node metastasis in m1 and m2 cancers were less than about 5 %, those of m3 and sm1 cancers were 12 - 27 %, while in sm2 and sm3 cancers the rates were 36 - 46 % [1]. Based on those findings, m1 and m2 tumors can be considered to be localized and therefore having a good indication for local treatment such as EMR. However, in order to select the most appropriate treatment for superficial cancer, especially about the indication for EMR, it is absolutely essential to have a precise evaluation of the depth of cancer invasion, with particular attention to discrimination between m1 and m2 tumors on the one hand and m3 and sm1 tumors on the other.
Platelet adhesion: a game of catch and release
Authors: Robert K. Andrews, Michael C. Berndt
Journal: Journal of Clinical Investigation (2008)

The interaction of circulating platelets with the vessel wall involves a process of cell catch and release, regulating cell rolling, skipping, or firm adhesion and leading to thrombus formation in flowing blood. In this regard, the interaction of platelet glycoprotein Ibα (GPIbα) with its adhesive ligand, vWF, is activated by shear force and critical for platelet adhesion to the vessel wall. In this issue of the JCI, Yago and colleagues show how gain-of-function mutations in the GPIbα-binding vWF A1 domain disrupt intramolecular interactions within WT vWF A1 that regulate binding to GPIbα and flow-enhanced platelet rolling and adhesion (see the related article beginning on page 3195). Together, these studies reveal molecular mechanisms regulating GPIbα-vWF bond formation and platelet adhesion under shear stress.
Reply from authors re: Monique J. Roobol, Eveline A.M. Heijnsdijk. Propensity Score Matching, Competing Risk Analysis, and a Competing Risk Nomogram: Some Guidance for Urologists May Be in Place. Eur Urol 2011;60:931–3
Authors: Maxine Sun, Firas Abdollah, Pierre I. Karakiewicz
Journal: European Urology (2011)
Up-regulation of Inflammatory Signalings by Areca Nut Extract and Role of<i>Cyclooxygenase-2</i>−1195G&amp;gt;A Polymorphism Reveal Risk of Oral Cancer
Authors: Shang-Lun Chiang, Ping-Ho Chen, Chien-Hung Lee, Albert Min-Shan Ko, Ka-Wo Lee, Ying-Chu Lin, Pei-Shan Ho, Hung-Pin Tu, Deng-Chyang Wu, Tien-Yu Shieh, Ying-Chin Ko
Journal: Cancer Research (2008)

Abstract Because the mRNA expression of cyclooxygenase-2 (COX-2) is up-regulated by arecoline in human gingival fibroblasts, as shown in our previous study, we further investigated the mRNA expression level of COX-2 and its upstream effectors in three oral epithelial carcinoma cell lines (KB, SAS, and Ca9-22) by using areca nut extract (ANE) and saliva-reacted ANE (sANE). A case-control study of 377 oral squamous cell carcinoma (OSCC) patients and 442 controls was conducted to evaluate the gene-environment interaction between COX-2 promoter polymorphisms and substance use of alcohol, betel quid, and cigarettes (ABC) in risk of OSCC. The heterogeneous characteristics of the oral site and the COX-2 −1195G&amp;gt;A polymorphism in these cell lines showed diverse inflammatory response (KB≫Ca9-22&amp;gt;SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-κB activation. In the case-control study, betel chewing [adjusted odds ratios (aOR), 42.2] posed a much higher risk of OSCC than alcohol drinking and cigarette smoking (aORs, 2.4 and 1.8, respectively), whereas the COX-2 −1195A/A homozygote presented a potential genetic risk (OR, 1.55). The strongest joint effect for OSCC was seen in betel chewers with −1195A/A homozygote (aOR, 79.44). In the non–betel chewing group, the −1195A/G and A/A genotypes together with the combined use of alcohol and cigarettes increased risk to 15.1-fold and 32.1-fold, respectively, compared with the G/G genotype without substance use. Taken together, these findings illustrate a valuable insight into the potential role of the COX-2 promoter region in contributing to the development of betel-related OSCC, including ANE/sANE–induced transcriptional effects and enhanced joint effects of COX-2 −1195A allele with substance use of ABC. [Cancer Res 2008;68(20):8489–98]
Sing and dance
Authors: D. Spence
Journal: BMJ (2011)

My brother held the dog by the front paws so that he stood on his hind legs. The dog was barking wildly as they danced into the room. We Close Our Eyes by Go West blasted out. “This is a fantastic song!” I was sitting on my bed. “It’s bollocks,” I said, and returned to my revision. We shared a small room all our childhood. We played music all the time. First our older brother’s scratched Led Zeppelin, ELO, and Dr Hook albums. Music was expensive; we took what we could get. …
The mediation of platelet quiescence by NO-releasing polymers via cGMP-induced serine 239 phosphorylation of vasodilator-stimulated phosphoprotein
Authors: Terry C. Major, Hitesh Handa, Elizabeth J. Brisbois, Melissa M. Reynolds, Gail M. Annich, Mark E. Meyerhoff, Robert H. Bartlett
Journal: Biomaterials (2013)
Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis
Authors: N. Latimer, J. Lord, R. L Grant, R. O'Mahony, J. Dickson, P. G Conaghan
Journal: BMJ (2009)

To investigate the cost effectiveness of cyclo-oxygenase-2 (COX 2) selective inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs), and the addition of proton pump inhibitors to these treatments, for people with osteoarthritis.An economic evaluation using a Markov model and data from a systematic review was conducted. Estimates of cardiovascular and gastrointestinal adverse events were based on data from three large randomised controlled trials, and observational data were used for sensitivity analyses. Efficacy benefits from treatment were estimated from a meta-analysis of trials reporting total Western Ontario and McMaster Universities (WOMAC) osteoarthritis index score. Other model inputs were obtained from the relevant literature. The model was run for a hypothetical population of people with osteoarthritis. Subgroup analyses were conducted for people at high risk of gastrointestinal or cardiovascular adverse events. Comparators Licensed COX 2 selective inhibitors (celecoxib and etoricoxib) and traditional NSAIDs (diclofenac, ibuprofen, and naproxen) for which suitable data were available were compared. Paracetamol was also included, as was the possibility of adding a proton pump inhibitor (omeprazole) to each treatment.The main outcome measure was cost effectiveness, which was based on quality adjusted life years gained. Quality adjusted life year scores were calculated from pooled estimates of efficacy and major adverse events (that is, dyspepsia; symptomatic ulcer; complicated gastrointestinal perforation, ulcer, or bleed; myocardial infarction; stroke; and heart failure).Addition of a proton pump inhibitor to both COX 2 selective inhibitors and traditional NSAIDs was highly cost effective for all patient groups considered (incremental cost effectiveness ratio less than pound1000 (euro1175, $1650)). This finding was robust across a wide range of effectiveness estimates if the cheapest proton pump inhibitor was used. In our base case analysis, adding a proton pump inhibitor to a COX 2 selective inhibitor (used at the lowest licensed dose) was a cost effective option, even for patients at low risk of gastrointestinal adverse events (incremental cost effectiveness ratio approximately pound10 000). Uncertainties around relative adverse event rates meant relative cost effectiveness for individual COX 2 selective inhibitors and traditional NSAIDs was difficult to determine.Prescribing a proton pump inhibitor for people with osteoarthritis who are taking a traditional NSAID or COX 2 selective inhibitor is cost effective. The cost effectiveness analysis was sensitive to adverse event data and the specific choice of COX 2 selective inhibitor or NSAID agent should, therefore, take into account individual cardiovascular and gastrointestinal risks.
A CASE OF TYPHOID FEVER WITH AN UNUSUAL COMPLICATION.
Authors: WILLIAM EDGAR DARNALL
Journal: JAMA (1904)

Hemorrhage as a complication of typhoid fever presents some interesting phases. The literature on the subject of enteric fever abounds with discussions of hemorrhage from almost every organ in the body, but the uterus seems to have been overlooked. In the literature at my command I have been able to find but very little. By most authorities on the subject no mention whatever is made of uterine hemorrhage as a complicacation of typhoid fever. Osler, however, does mention "a rare and fatal form of typhoid fever characterized by cutaneous and mucous hemorrhages." Montgomery, in his work on gynecology, draws attention to the fact that "severe uterine hemorrhage may frequently usher in an attack of typhoid fever," and this is not uncommon, especially if it happens to be about the time of the normal menstrual flow. In the case, however, presented here for your consideration, the hemorrhage did not usher