tbuckley/cabot-search huggingface dataset:
Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells
Authors: H Hasegawa, Y Yamada, H Iha, K Tsukasaki, K Nagai, S Atogami, K Sugahara, K Tsuruda, A Ishizaki, S Kamihira
Journal: Leukemia (2009)
Fibrinogen Cleveland II AN ABNORMAL FIBRINOGEN WITH DEFECTIVE RELEASE OF FIBRINOPEPTIDE A
Authors: Edward D. Crum, John R. Shainoff, Richard C. Graham, Oscar D. Ratnoff
Journal: Journal of Clinical Investigation (1974)

An abnormal fibrinogen (fibrinogen Cleveland II) was detected in the plasma of a 23-yr-old white man with a mild bleeding diathesis. The one-stage prothrombin time, thrombin time, and Reptilase time were all prolonged. 16 of 24 tested relatives had the defect, which appeared to be transmitted as an autosomal dominant characteristic. The thrombin time of normal plasma was slightly inhibited by the proband's plasma. The abnormally long thrombin time of fibrinogen Cleveland II was partially corrected by addition of calcium ions. Fibrinogen Cleveland II was indistinguishable from normal fibrinogen by immunoelectrophoresis, DEAE-cellulose column chromatography, or polyacrylamide gel electrophoresis of reduced fibrinogen in sodium dodecyl sulfate. The major defect detected appeared to be impaired release of fibrinopeptide A when fibrinogen Cleveland II was incubated with thrombin. This defect was localized to the NH2-terminal disulfide knot portion of the molecule. An abnormality of polymerization of fibrin monomers was also present, but the abnormal fibrin demonstrated relatively normal crosslinking. Despite these defects, fibrinogen Cleveland II achieved a degree of coagulability similar to normal fibrinogen and appeared to incorporate some molecules of fibrin with intact fibrinopeptide A into the clot. The fibrin clot that was formed appeared to be abnormal by electron microscopy. These functional defects and other descriptive characteristics appear to distinguish fibrinogen Cleveland II from other inherited abnormal fibrinogens.
Abstract 2729: A genetically engineered mouse model of de novo pancreatic carcinogenesis .
Authors: Takashi Yamaguchi, Sanae K. Ikehara, Yuzuru Ikehara
Journal: Cancer Research (2013)

Abstract Multistep models of PDAC development converge on both abnormalities in KRAS and E2F activation, which are part of the Rb/E2F pathway, and dysfunction of p53, which is associated with the MDM2/p53 pathway. Recent progress in the understanding of the protective roles of the Rb/E2F and MDM/p53 pathways against carcinogenesis showed that cross talk and complementary actions of these pathways are present in many types of cancers. In this study, we addressed directly questions regarding the collaborative roles of the Rb/E2F and MDM2/p53 pathways in suppressing the progression of multistep PDAC carcinogenesis by generating TKC (loxP-βgeo-STOP-loxPtemperature-sensitive SV40 T antigen (tsTAg)), loxP-STOP-loxP-KrasG12D, and Pdx1-Cre) mice which exhibit impairment of both pathways and K-rasG12D expression in pancreatic epithelial cells. The PDAC induced in TKC mice exhibited rapid development and absence of inflammation or PanIN formation, which occurred by de novo carcinogenesis. The tumors resembled human PDAC at the histological and molecular level. In in vitro study, we established PDAC cell lines from TKC mice and immortalized pancreatic ductal cell lines from TC mice, Cytokeratin 19 expression with which was applied to select cells as pancreatic ductal cell differentiation. In collagen gel 3D culture, PDAC cells formed atypical gland structures the same as in subcutaneous transplanted tumor in nude mice, while the Cytokeratin 19 positive immortalized ductal cell lines from TC mice formed ductal structures similar to either intralobular or interloblar pancreatic ducts. The results of the analysis of the highlighted molecular mechanisms suggest that the synthetic interaction among mutated Kras, uncontrolled E2f activation, and dysfunction of p53 results in de novo pancreatic carcinogenesis. This model represents an important tool to explore molecular targets for diagnostics and cancer therapy for PDAC via de novo pancreatic carcinogenesis.This work was supported by grants from the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN) and New Energy and Industrial Technology Development Organization (NEDO) of Japan, and supported in part by Grants-in-Aid for Scientific Research on Priority Area (21590454, 24590498, and 24108006 to Y. I.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Citation Format: Takashi Yamaguchi, Sanae K. Ikehara, Yuzuru Ikehara. A genetically engineered mouse model of de novo pancreatic carcinogenesis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2729. doi:10.1158/1538-7445.AM2013-2729
Hypercalcemia and Tuberculosis
Authors: Om P. Sharma
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Hypercalcemia is an unusual finding in tuberculosis. At this medical center, we have recently seen a transient hypercalcemia in a patient with tuberculosis. <h3>Report of a Case.—</h3> A 24-year-old Indian was admitted to the general medical ward from a tuberculosis care center because of an elevated serum calcium level. The diagnosis of tuberculosis was made six weeks earlier on the basis of a history of fever and weight loss, x-ray films of the chest consistent with a miliary process, positive intermediate strength purified protein derivative (PPD), and a positive sputum culture for acid-fast bacillus. Chemotherapy consisted of isoniazid, streptomycin, pyridoxine, and PAS (powder—not the calcium salt). The SMA-12 detected two hypercalcemic sera, and transfer to the medical service was subsequently recommended. The hypercalcemia, in addition to azotemia and elevated creatinine level, was confirmed on initial work-up. Significant laboratory data appear in the Table. Sarcoidosis was ruled out
Depressive Symptoms and the Risk of Atherosclerotic Progression Among Patients With Coronary Artery Bypass Grafts
Authors: Gregory A. Wellenius, Kenneth J. Mukamal, Ambar Kulshreshtha, Sharon Asonganyi, Murray A. Mittleman
Journal: Circulation (2008)

Background— Depressive symptoms have been associated with increased risk of coronary artery disease and poor prognosis among patients with existing coronary artery disease, but whether depressive symptoms specifically influence atherosclerotic progression among such patients is uncertain. Methods and Results— The Post-CABG Trial randomized patients with a history of coronary bypass graft surgery to either an aggressive or a moderate lipid-lowering strategy and to either warfarin or placebo. Coronary angiography was conducted at enrollment and after a median follow-up of 4.2 years. Depressive symptoms were assessed at enrollment with the Centers for Epidemiologic Studies Depression scale (CES-D) in 1319 patients with 2496 grafts. In models that adjusted for age, gender, race, treatment assignment, and years since coronary bypass graft surgery, a CES-D score ≥16 was positively associated with risk of substantial graft disease progression (OR 1.50, 95% CI 1.08 to 2.10, P =0.02) and marginally associated with a 0.11-mm (95% CI −0.22 to 0.01 mm, P =0.07) decrease in minimum lumen diameter, but not with risk of graft occlusion ( P =0.30). Additional adjustment for past medical history, blood pressure, and renal function did not materially alter these results. This association was virtually absent among participants randomly assigned to aggressive lipid-lowering therapy. Conclusions— These findings suggest that depressive symptoms are associated with a higher risk of atherosclerotic progression among patients with saphenous vein grafts and that aggressive lipid lowering can minimize this increased risk. Whether depressive symptoms increase progression in other types of coronary atherosclerosis and whether aggressive lipid lowering attenuates such progression will require additional study.
Inhibition of the IL-4/IL-13 receptor system prevents allergic sensitization without affecting established allergy in a mouse model for allergic asthma
Authors: Christian Hahn, Martin Teufel, Udo Herz, Harald Renz, Klaus J. Erb, Gisela Wohlleben, Eva B. Bröcker, Albert Duschl, Walter Sebald, Susanne M. Grunewald
Journal: Journal of Allergy and Clinical Immunology (2003)
Clinical Trial of Lincomycin Hydrochloride in Reiter's Disease
Authors: K. Whaley, W. W. Downie, W. C. Dick, G. Nuki, C. B. S. Schofield, J. Anderson
Journal: BMJ (1969)

A double-blind trial comparing lincomycin hydrochloride (Mycivin) and placebo in 22 patients with Reiter's disease showed no significant difference in clinical or laboratory findings between the two groups. It is concluded that lincomycin hydrochloride is no more effective than placebo in the treatment of Reiter's disease.
CASE OF HERNIOTOMY
Authors: J. McIntyre
Journal: BMJ (1854)

XMO~SInSyte of asn one ease, ilW h mn d muo o mom-~Ua white, opaque, and cov wti white curdy Boo- emI, resembling a surface afeed with diphtheritic m_ The Falopian were more frequently than any other of the uterine asytem congested nd echymosed-the Id being frequently extravasated in the form of zones or imp.In two cases, gelatiniform cysts were developed at r extremities, containing yellow glutinous matter, so vicid as to require considerable force for its extrusion.In Ahe ovaries were frequently found patches of humorrhagic xstravasation, seated on the surface or in the centre of old ra utea.In some cases, they were shrunk, atrophied, «an hard; in others, they were the seat of cystic degenera- tion.The cysts varied in size, in the thickness of their walls, and the colour and consistence of their contents.The largest I saw was the size of a walnut, and contained a dark claret-coloured fluid; others were smaller, and con- tained a gelatiniform mucus.[To be continued.l
A Discussion on Therapeutic Modification of the Diet in Infancy
Authors: H. C. Cameron
Journal: BMJ (1927)

DEBATES Upon the subject of infant feedinig seldom arouse profitable discussion.As a rule they serve to make clear olyly the difficulty of reconciling the view-s of those wlho might be supposed to speak with authority.Therefore, in the first h)lace, I would ask the question: Wlherein lies the difficulty and complexity of the subject?Why is it that in this suibject, on the importanice of which all are agreed, ojpinion has remained so fluid, anld so little that is solid and concrete has crystallized out from it?Why is it that, in l)ractice, we still encounter, on the onie hand, a frenzied search among a host of proprietary foods for one which may act up to the promises of all, or, on the other hand, a too rigidl adhesion to some one system of feeding, despite the persistence of symptoms.Difficulties Inherent in the Subject.It is obxious that some of the difficulties with which we hiave to contend are inlherent in the subject itself.In
Polymer surface functionalities that control human embryoid body cell adhesion revealed by high throughput surface characterization of combinatorial material microarrays
Authors: Jing Yang, Ying Mei, Andrew L. Hook, Michael Taylor, Andrew J. Urquhart, Said R. Bogatyrev, Robert Langer, Daniel G. Anderson, Martyn C. Davies, Morgan R. Alexander
Journal: Biomaterials (2010)
Identification of protein-tyrosine kinase catalytic domain conserved sequences in the ORF expressed sequence tags database
Authors: Daniel Giannella-Neto, Maria Lúcia C. Correa, Ana Mercedes S. Cavaleiro-Luna, Maria Angela H.Z. Fortes, Cassio N. Coimbra, Leonardo S. Oliveira, Sandro J. De Souza, Andrew J.G. Simpson
Journal: Nature Genetics (2001)
The Truth and Consequences of the COURAGE Trial
Authors: Dean J. Kereiakes, Paul S. Teirstein, Ian J. Sarembock, David R. Holmes, Mitchell W. Krucoff, William W. O’Neill, Ron Waksman, David O. Williams, Jeffrey J. Popma, Maurice Buchbinder, Roxana Mehran, Ian T. Meredith, Jeffrey W. Moses, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2007)
Evidence based medicine: flawed system but still the best we've got
Authors: F. Godlee
Journal: BMJ (2014)

Evidence based medicine is so much part of the air we breathe it can be hard to remember a time before it. An oral history, filmed for a joint JAMA and BMJ celebration last year, has now been published on bmj.com/evidence and the JAMA network. As summarised in an editorial co-published by the two journals this week, the story features a satisfying array of heroes and detractors, forward progress and backlash (doi:10.1136/bmj.g371).

Why did evidence based medicine take off? In the video, and quoted in the editorial, David Sackett provides two main reasons: …
Bronchial asthma due to alpha-methyldopa.
Authors: M G Harries, A N Taylor, J Wooden, A MacAuslan
Journal: BMJ (1979)

iron-storage disease, malignant disease, and a history of neck surgery or irradiation.Bone biopsy was not performed in either case because of the absence of any biochemical or radiological evidence of osteo- malacia.Our first case is the oldest known patient to present with this disorder, the oldest described elsewhere being an 80-year-old man who presented with confusion.4Little is known about parathyroid function in the elderly, but we suggest that these cases might represent extreme examples of an age-related decline in parathyroid function.The clinical features of hypocalcaemia are less dramatic in the elderly5 and may easily be ascribed to irremediable causes, such as cerebrovascular disease.We therefore recommend that hypocalcaemia, which is disabling but remediable, should be more often sought in elderly patients, particularly those presenting with confusional states or epilepsy.
Viruses and Multiple Sclerosis
Authors: Victor M. Rivera
Journal: JAMA (1977)

To the Editor.—  Gokcen and Cox (237:1311, 1977) observed that SV-40 virus and arboviruses could produce type IV hyperlipidemia in experimental animals and that viral upper respiratory tract infections in patients with coronary artery disease may produce transient type IV hyperlipoproteinemias.  Reports about diverse lipid abnormalities detectable in the serum and in the cerebrospinal fluid of patients with multiple sclerosis (MS) have accumulated in recent years. Total cholesterol level has been reported to be increased during remission, while the total amount of lipidphosphorus is reduced in the stationary stages of the disease. 1 The percentage of linoleate in the phospholipids of platelets and erythrocytes has been shown to be substantially reduced. 2 In view of these findings, a serum lipid profile has been performed in 60 MS patients selected at random. Almost half of the patients (N-29; 48.3%) had hyperlipoproteinemias: 17 patients had type IV, 8 patients had type IIa,
Homicide Among Adolescents in the United States
Authors: Lois A. Fingerhut
Journal: JAMA (1991)

<h3>To the Editor.</h3> —The review by Dr Blum<sup>1</sup>of adolescent health contains inaccurate and incomplete homicide data for the United States. Homicide was not the third leading cause of death but was the 12th leading cause for the total population in 1987 and in 1988. However, for persons aged 15 through 24 years, homicide ranked as the second leading cause of death (following unintentional injuries) in 1986, 1987, and 1988. The rate of 21.9 deaths per 100 000 persons, as cited by Blum, is the 1987 homicide rate for males aged 15 through 24 years, as reported in the study by Fingerhut and Kleinman,<sup>2</sup>which was not referenced by Blum. Blum is correct in pointing out the racial differences in homicide for those aged 15 through 24 years. The rate cited, 79.2 per 100 000, is the 1986 rate for black males in that age group. The 1987
Intrathymic Parathyroid Adenoma
Authors: &NA; D. NGUYEN, MICHAEL C. ROARKE, NELS A. DUTTON
Journal: Clinical Nuclear Medicine (2000)

In a 67-year-old woman who had primary hyperparathyroid disease, planar and SPECT sestamibi scintigraphy showed a right lower cervical–upper mediastinal parathyroid adenoma that was confirmed by surgery to be intrathymic. Surgery also found a concomitant left normal intrathymic parathyroid gland. Intrathymic parathyroid adenoma is reviewed briefly and discussed.
GMC faces potential legal challenge over failure to investigate alleged cover-up
Authors: C. Dyer
Journal: BMJ (2009)

The General Medical Council is facing a High Court challenge over its refusal to investigate allegations of a cover-up by doctors after the death of a 10 year old boy from Addison’s disease in 1990.

The campaign group Action against Medical Accidents (AvMA) is to ask the court next week for permission to seek a judicial review of the GMC’s refusal to investigate the circumstances surrounding the death of Robbie Powell.

Five general practitioners at a health centre in Ystradgynlais, Powys, and a consultant paediatrician at Morriston Hospital, Swansea, had seen Robbie in the weeks before his death but failed to diagnose Addison’s disease, which is rare in children. …
Effects of allergen challenge on eosinophils, eosinophil cationic protein, and granulocyte-macrophage colony-stimulating factor in mild asthma.
Authors: K L Woolley, E Adelroth, M J Woolley, R Ellis, M Jordana, P M O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Allergen inhalation challenge is associated with increases in eosinophil number and activation, and provides a useful model for investigating airway inflammation in asthma. Limited information, however, is available on the effect of allergen challenge on cytokines regulating eosinophil function. We investigated allergen-induced changes in eosinophil number and activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine known to regulate eosinophil function in vitro. Seven subjects with mild atopic asthma and late asthmatic responses completed diluent- and allergen-inhalation challenges. Blood, bronchoalveolar lavage fluid (BALF), and biopsy samples were collected 24 h after challenge. Allergen inhalation caused a significant increase in eosinophils in BALF and biopsy samples. Eosinophil activation, as assessed by secretion of eosinophil cationic protein, and GM-CSF levels were significantly increased in BALF and bronchoalveolar lavage (BAL) cells. Allergen inhalation did not cause a significant change in eosinophil activation in biopsy tissue but did result in a significant decrease in GM-CSF in the tissue. Significant correlations were shown between the concentration of GM-CSF in BALF and the percentage of BAL eosinophils (Rs = 0.75, p = 0.05), severity of the late asthmatic response, and number of BAL eosinophils (Rs = 0.82, p = 0.02). A trend was seen between the late response and the concentration of GM-CSF in BALF. These results are consistent with the hypothesis that eosinophils, regulated by GM-CSF, contribute to allergen-induced decreases in airway function.
Glycoprotein IIb/IIIa Receptor Blockade Improves Outcomes in Diabetic Patients Presenting With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Authors: Pierre Théroux, Joe Alexander, Chantal Pharand, Eliav Barr, Steven Snapinn, Asma F. Ghannam, Frederic L. Sax
Journal: Circulation (2000)

Background —Diabetic patients who present with unstable angina or non–ST-elevation myocardial infarction suffer a substantially greater incidence of subsequent infarction or death compared with nondiabetic patients. The present study was undertaken to examine whether diabetic patients in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study appeared to benefit from platelet glycoprotein IIb/IIIa receptor–mediated inhibition of platelet aggregation by tirofiban. Methods and Results —Of the 1570 PRISM-PLUS patients treated with either tirofiban plus heparin (n=773) or heparin alone (n=797), ≈23% in each treatment group were diabetic. A comparison of treatment outcomes in the diabetic subgroup revealed that the combination therapy compared with heparin alone was associated with reductions in the incidence of the composite primary end point of death, myocardial infarction (MI), or refractory ischemia at 2, 7, 30, and 180 days (7.7% versus 8.3%, 14.8% versus 21.8%, 20.1% versus 29.0%, and 32.0% versus 39.9%, respectively; P=NS) and in the incidence of MI or death (0.0% versus 3.1%, P =0.03; 1.2% versus 9.3%, P =0.005; 4.7% versus 15.5%, P =0.002; and 11.2% versus 19.2%, P =0.03). Tests for quantitative interaction between tirofiban therapy and diabetic status were significant. Conclusions —The addition of tirofiban to heparin and aspirin appears effective in the prevention of major ischemic events, particularly MI or death, in diabetic patients presenting with unstable angina and non–ST-elevation MI.
A case-control study of cervical cancer screening in north east Scotland.
Authors: J E Macgregor, S M Moss, D M Parkin, N E Day
Journal: BMJ (1985)

To estimate the relative risk of invasive cervical cancer in each succeeding year after a negative screening result the screening records of all women tested in the north east of Scotland were examined as the basis for a case-control study. The cases consisted of 115 women in whom invasive cervical cancer had been diagnosed in 1968-82 and who had appeared in the screening records at least once before diagnosis. For each patient five controls were selected from women of the same age who appeared in the screening records before the date of diagnosis in the patient. If the patient9s cancer had been detected by screening the controls were chosen from women of the same age screened the same year. A comparison was made between cases and controls of the number of negative smears taken before the diagnosis. The results showed a high relative protection (inverse of the relative risk) in the first two years after a negative test, falling steadily as time since the last negative test elapsed. Even after 10 years, however, a considerable residual effect was observed.
Growing Green Roofs, City by City
Authors: David A. Taylor
Journal: Environmental Health Perspectives (2007)

reen roofs-rooftops that are partially or completely covered with vegetation growing in soil medium over a waterproof membrane-have gained momentum over the past six years as building owners recognize their advantages over conventional roofing in terms of better energy efficiency and reduced rain runoff.Now local governments are exploring incentives for moving the practice into the mainstream.A look at cities that are leading the country in green roof coverage reveals a growing range of policy tools.