tbuckley/cabot-search huggingface dataset:
A UK-WIDE AUDIT OF THE EFFECTIVENESS AND SAFETY OF ADALIMUMAB IN CHILDREN AND YOUNG PEOPLE WITH CROHN'S DISEASE
Authors: R. K. Russell, M. L. Wilson, N. Shah, G. Mahdi, W. Hyer, C. Spray, C. Daman, R. Heuschkel, N. A. Afzal, M. Elawad, F. Torrente, N. Ayub, J. M. E. Fell, G. Ho, S. Naik, D. C. Wilson
Journal: Gut (2009)
Angiography and LMCA stenosis.
Authors: J H Dixon
Journal: Circulation (1981)

between the femoral artery and the aorta.These observations could also be interpreted as an increase in the amount of reflections from the upper body but a decrease in the amount of reflection from the lower part of the body.These results remain consistent with the mechanisms we proposed if one accepts that the reflections from the lower part of the body are those that dominate the wave form con- tours in the ascending aorta.To decide what roles either a change in the amount or a change in the delay time of reflected waves from various parts of the body plays in determining the configuration of pressure wave forms outside of the ascending aorta, it would be necessary to study with solid-state micrometers and flow sensors the pressure-flow relationships in vessels other than the ascending aorta during control and during the Valsalva maneuver.Dr. O'Rourke implies that our results on phase angle of the im- pedance showed similar fluctuations and control during Valsalva.We do not quite understand this comment; both figures 3 and 4 of our study reveal phase angles that deviate less from zero during the maneuver as compared to control.This finding is consistent with the smooth impedance modulus and again indicates a decrease in reflec- tions during the Valsalva maneuver.Dr. O'Rourke's contributions to the field of arterial hemo- dynamics have been enormous and we have the greatest admiration for this distinguished scientist.His remarks have stimulated us to pursue these issues further and studies are under way in our laboratory to evaluate the role of reflections from the upper as well as the lower body using the advantages of modern multisensor catheterization techniques.
Cytochemical Bioassay of Parathyroid Hormone
Authors: David Goltzman, Brian Henderson, Nigel Loveridge
Journal: Journal of Clinical Investigation (1980)

A cytochemical bioassay for parathyroid hormone (PTH) was used for the characterization of the biological activity of circulating forms of the hormone. PTH-stimulated glucose-6-phosphate dehydrogenase activity in distal convoluted tubule cells was quantitated by integrating microdensitometry and the response to native bovine (b)PTH(1-84) was found to be linear between graded doses of hormone from 5 fg/ml to 5 pg/ml. Synthetic bPTH(1-34) and human (h)PTH(1-34) elicited a parallel and equimolar response; however calcitonin, ACTH, glucagon, epinephrine, vasopressin, and insulin failed to significantly stimulate the enzyme in doses up to 100,000 times greater than the lowest concentration of bPTH used. The assay was capable of distinguishing hormonal activity in normal, hypoparathyroid, and hyperparathyroid human plasma. After gel chromatography, bioactivity in plasma of hyperparathyroid patients with skeletal disease but normal kidney function coeluted mainly with bPTH(1-84), whereas bioactivity in plasma of hyperparathyroid patients with skeletal disease but severe uremia coeluted in approximately equivalent amounts with bPTH(1-84) and hPTH(1-34). Despite the abundance of small molecular-weight bioactivity in the peripheral circulation in uremia, ∼85% of the bioactivity in the parathyroid venous effluent coeluted with bPTH(1-84). The results therefore demonstrate the sensitivity and specificity of the assay for PTH and its utility in measuring the hormone in human parathyroid disorders. The results furthermore demonstrate the importance of entities cochromatographing with bPTH(1-84) in comprising the circulating bioactive hormone in hyperparathyroidism, and support the concept of a biological role for smaller forms of PTH, at least in chronic renal failure.
You and Others
Authors: Helen Shacter, W.W. Bauer, Guy Parker, Felix Traugott, Clara Ernst
Journal: JAMA (1949)

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
Radiation-induced activation of ErbB2, ErbB3 and IGF-1R in breast carcinoma cells expressing low EGFR levels
Authors: Xuemei Luo, Ross B. Mikkelsen
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4386 

Previous studies have demonstrated that ionizing radiation (IR) activates EGFR in diverse carcinoma cell lines both in vitro and in vivo as detected by enhanced Tyr autophosphorylation. Less studied are other members of the ErbB family and other receptor Tyr kinases such as IGF-1R. Downstream signaling from these receptor families through both the MAPK and PI3-K pathways has been shown to be critical in radioresistance mechanisms. In the present report we have examined activation of ErbB2/ErbB3 and IGF-1R in two breast cancer cell lines that express relatively low levels of EGFR (MCF-7 and T47D). Receptor activation was followed post-IR (3 Gy) or after ligand treatment (IGF-1 or heregulin) by immunoprecipitation with anti-phosphoTyr and blotting with the appropriate receptor antibodies. Immediate downstream signaling was monitored as Tyr phosphorylation of the adaptor protein, SHC, for all three receptors. SHC is in the MAPK signaling pathway. In addition, for IGF-1R, the phosphorylation state of the IRS adaptor protein (upstream of the PI3-K/Akt pathway) was determined as follows: Tyr phosphorylation as a measure of activation and Ser312 phosphorylation as a measure of inhibition. The tyrphostin inhibitors for ErbB2 and IGF-1R kinase activities were respectively, 5 μM AG 825, and 10 μM AG 1024. Initial experiments established time courses for the IR-induced activation of the receptors. Both ErbB2 and ErbB3 showed an initial transient increase in receptor phosphorylation centered at 5-10 min post-IR with a more sustained increase at time points between 30-120 mins. In contrast there was no evidence for IR-induced activation of IGF-1R although IGF-1 addition stimulated a robust increase in receptor Tyr phosphorylation.. IR-stimulated increased SHC Tyr phosphorylation consistent with the observed MAPK signaling observed in these cells after IR treatment. AG825, although effective in inhibiting IR-induced ErbB2 autophosphorylation, was without effect on IR-induced SHC phosphorylation. A 1 hr pre-treatment with 1AG1024 on the other hand blocked IR-stimulated SHC phosphorylation. Activation of IRS as measured by Tyr phosphorylation was not observed although Ser312 phosphorylation increased significantly as a consequence of an IR exposure. We propose that in cells that express low levels of EGFR exposure to low IR doses channels IGF-1R signaling into the cytoprotective pathway MAPK pathway. In keeping with our previous studies, anti-apoptotic PI3-K/Akt signaling, on the other hand, is predominantly a function of ErbB2/ErbB3 activity possibly because of the 6 PI3-K binding sites on ErbB3.
Abstract 3520: TAZ (WWTR1), a key transcription co-activator of hippo-pathway, promotes hepatocellular carcinoma progression via PI3K/Akt/mTOR pathway
Authors: Hiromitsu Hayashi, Hideyuki Kuroki, Shigeki Nakagawa, Takaaki Higashi, Keita Sakamoto, Naomi Yokoyama, Takatoshi Ishiko, Toru Beppu, Hideo Baba
Journal: Cancer Research (2014)

Abstract Introduction: The contact inhibition of proliferation is crucial for well-controlled organogenesis. Its disruption results in sustained cell proliferation, which is a hallmark of solid tumors. The Hippo signaling pathway has been implicated in contact inhibition of proliferation. Here, we investigated the role of TAZ (WWTR1), a key transcription co-activator of hippo-pathway, in HCC progression. Methods and Results: In HCC patients, the high TAZmRNA expression examined by real time PCR showed worsen survival outcomes compared with low expression group. Additionally, the tumor size in High TAZmRNA expression group was significantly larger than that in low expression group, and its high protein expression in HCC was deeply associated with the cell proliferative activity. A knockdown of TAZ expression in HCC cell lines attenuated the cell growth accompanying the downstream gene expressions (CTGF and CYR61). As the TAZ-mediated signaling pathway in cell growth, a knockdown of TAZ expression using RNAi inactivated the PI3K/Akt/mTOR pathway. Conclusion: Thus, TAZ plays a crucial role in tumor progression by accelerating cell growth via a PI3K/Akt/mTOR pathway, and tumoral TAZmRNA expression level may be a useful prognostic biomarker in HCC. Citation Format: Hiromitsu Hayashi, Hideyuki Kuroki, Shigeki Nakagawa, Takaaki Higashi, Keita Sakamoto, Naomi Yokoyama, Takatoshi Ishiko, Toru Beppu, Hideo Baba. TAZ (WWTR1), a key transcription co-activator of hippo-pathway, promotes hepatocellular carcinoma progression via PI3K/Akt/mTOR pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3520. doi:10.1158/1538-7445.AM2014-3520
Adalimumab therapy rapidly inhibits p38 mitogen-activated protein kinase activity in lesional psoriatic skin preceding clinical improvement
Authors: L. Soegaard-Madsen, C. Johansen, L. Iversen, K. Kragballe
Journal: British Journal of Dermatology (2010)

Background The pathogenesis of psoriasis and the mechanisms of action of antitumour necrosis factor (TNF)-α therapies are incompletely understood. Objectives To investigate the early molecular effects of adalimumab in psoriatic skin. Methods Biopsies taken from patients with psoriasis were examined before and after the onset of adalimumab therapy. TNF-α protein level and mRNA expression were measured by enzyme-linked immunosorbent assay and quantitative reverse transcription–polymerase chain reaction, respectively. The activities of p38 mitogen-activated protein kinase (MAPK) and extracellular regulated kinase 1 and 2 (ERK1/2) as well as the downstream kinases MAPK-activated protein kinase 2 (MK2) and mitogen- and stress-activated protein kinase 1 and 2 (MSK1/2) were measured by Western blot analyses. Results We demonstrated that clinical and histological improvements were detected from day 14. The increased activity of p38 MAPK in lesional psoriatic skin was significantly inhibited by adalimumab already at day 4. The activities of ERK1/2, MSK1/2 and MK2 were reduced at the end of study (day 84) when the level of TNF-α in lesional psoriatic skin reached the nonlesional level, and the Psoriasis Area and Severity Index score was reduced. Conclusions The rapid inhibition of p38 MAPK by adalimumab in lesional psoriatic skin preceded clinical and histological improvements, demonstrating an association between TNF-α neutralization and p38 MAPK inhibition. Thus, inhibition of p38 MAPK may be a novel mechanism by which adalimumab mediates its antipsoriatic effect.
Trends in the Risks and Benefits to Patients With Cancer in Phase 1 Clinical Trials
Authors: Susan Ross
Journal: JAMA (2005)

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
Drug points: Quinolones may induce hepatitis
Authors: S E Jones, R H Smith
Journal: BMJ (1997)

Objective: To examine the research evidence for the health consequences of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure.Design: A systematic review of published research, studies being identified by searching Medline (1966-96), Embase (1974-96), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1982-95); scanning citations; and consulting experts.Studies in all languages were considered which either investigated the association between obstructive sleep apnoea in adults and key health outcomes or evaluated the effectiveness of treatment of obstructive sleep apnoea with continuous positive airways pressure in adults.Main outcome measures: Mortality, systematic hypertension, cardiac arrhythmias, ischaemic heart disease, left ventricular hypertrophy, pulmonary hypertension, stroke, vehicle accidents, measures of daytime sleepiness, and quality of life.Results: 54 epidemiological studies examined the association between sleep apnoea and health related outcomes.Most were poorly designed and only weak or contradictory evidence was found of an association with cardiac arrhythmias, ischaemic heart disease, cardiac failure, systemic or pulmonary hypertension, and stroke.Evidence of a link with sleepiness and road traffic accidents was stronger but inconclusive.Only one small randomised controlled trial evaluated continuous positive airways pressure.Five non-randomised controlled trials and 38 uncontrolled trials were identified.Small changes in objectively measured daytime sleepiness were consistently found, but improvements in morbidity, mortality, and quality of life indicators were not adequately assessed.Conclusions: The relevance of sleep apnoea to public health has been exaggerated.The effectiveness of continuous positive airways pressure in improving health outcomes has been poorly evaluated.There is enough evidence suggesting benefit in reducing daytime sleepiness in some patients to warrant large randomised placebo controlled trials of continuous positive airways pressure versus an effective weight reduction programme and other interventions.
Abstract 11: Molecular mechanisms of inverse association between cancer and Alzheimer's disease
Authors: Yoosoo Yang, EunJung Lee, In-San Kim
Journal: Cancer Research (2015)

Abstract Apoptosis has been implicated in both cancer and neurodegenerative disease such as Alzheimer's disease (AD). Defective or inefficient apoptosis is an acquired hallmark of cancer cells, while cytochrome c-dependent apoptosis is a crucial pathway in AD related neuronal cell death. Notably, recent studies have revealed an inverse correlation between development of cancer and AD—AD patients show a reduced risk of cancer, while cancer survivors are less likely to acquire AD. Here we propose that amyloid β (Aβ), a widely accepted pathological culprit of AD, hijacks the intrinsic apoptotic pathway eliciting different symptoms for cancer and AD. By developing an in vitro single-vesicle cytochrome c release assay, we show that even in the absence of death signal the oligomeric form of synthetic Aβ directly interacts with a pro-apoptotic bcl-2 family protein BAK and induces apoptotic pores sufficient for cytochrome c release. Furthermore, Aβ oligomers not only cause neuronal cell death in HT-22 cells but also the apoptotic effect was significantly reduced with suppressed BAK expression via siRNA, further substantiating its apoptotic interaction with BAK. Moreover, a significant reduction of cytochrome c release was also observed with isolated mitochondria from BAK siRNA-treated HT-22 cells which specifically identifies the target machinery. These results demonstrate Aβ oligomers’ efficacy as a potent apoptotic ligand. In collection, we suggest that while Aβ oligomers may cause neuronal cell death in AD it may also ameliorate tumor proliferation in relation to cancer. Thus, providing molecular level evidence for the inverse association reported between cancer and AD patients. Citation Format: Yoosoo Yang, EunJung Lee, In-San Kim. Molecular mechanisms of inverse association between cancer and Alzheimer's disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 11. doi:10.1158/1538-7445.AM2015-11
Target-driven drug and diagnostic development: Lessons from HER2
Authors: Robert Cohen
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

PL02-03 

An increasing number of targeted therapies for cancer have reached the market or entered development in the past decade. Many of these treatments target molecular defects present only within a subset of a particular type of histologically-identifiable cancer. The need to identify such sub-populations creates complexities for both development and commercialization of new targeted agents. Genentech's successful development of Herceptin, a HER2-targeted humanized monoclonal antibody, can be viewed as an early and instructive example of the challenges facing the field.    Early work in the 1980's by Dennis Slamon and his collaborators demonstrated that significant genomic amplification of the HER2 locus was present in approximately 20% of ductal carcinomas of the breast. Genomic amplification was shown to be associated with overexpression of the HER2 oncoprotein on the surface of tumor cells and breast cancer cell lines. Overexpression was also shown to be required for anti-proliferative responses to anti-HER2 antibodies. Herceptin was therefore developed specifically for tumors in which HER2 is overexpressed and clinical development included only such patients. The implications of this strategy will be discussed, focusing on the need for high-quality, reliable, accessible diagnostics during development and commercialization of targeted anti-cancer agents. Broader implications of targeted treatment approaches for the rational pathologic classification of cancers will also be considered. An update on the diagnostic approaches being taken to support the development of newer treatments directed at HER pathways will be presented.
Sixth formers gamble over medical school choices
Authors: S B Fazel, M W Hughes
Journal: BMJ (1995)

EDITOR,—Aneez Esmail and colleagues surveyed the acceptances of A level students by medical schools in 1992, comparing white applicants and those from ethnic minorities.1 The same data, if the two groups are amalgamated, give the overall ratio of applicants to places for each medical school. These ratios are, of course, the chances of an applicant with a given A level score …
Abstract P347: Risk of Incident Coronary Heart Disease Events in Men Compared to Women by Menopause Type and Race
Authors: Catherine Kim, Mary Cushman, Yulia Khodneva, Lynda D Lisabeth, Suzanne Judd, Dawn O Kleindorfer, Virginia J Howard, Monika M Safford
Journal: Circulation (2015)

Introduction: Men have greater risk of coronary heart disease (CHD) compared to women. It is unclear whether type of menopause affects this sex difference and if the impact is similar in blacks and whites. Moreover, women and their physicians may consider CHD risk when considering whether elective hysterectomy and/or bilateral salpingo-oophorectomy (BSO) are performed. Hypotheses: Women who undergo natural menopause, menopause due to BSO, and menopause due to hysterectomy alone have different risks of non-fatal CHD and acute CHD death compared to men. Methods: Participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007 without CHD at baseline (n=23,086), with follow-up through December 2011. Cox proportional hazard models were used to calculate the hazard of incident CHD events in men vs. women by menopause type, stratified by black vs. white race. The main outcome measure was adjudicated incident CHD events, defined as nonfatal CHD (definite or probably myocardial infarction) and acute CHD death. Results: Over a median 6.0 years of follow-up, 892 incident CHD events occurred. Cox regression models adjusted for age, age at last menstrual period &lt; 45 years, region, education level, income, CHD risk factors (total cholesterol, high-density lipoprotein, smoking, systolic blood pressure, diabetes, albumin to creatinine ratio, physical activity, C-reactive protein, body mass index and waist circumference), and use of anti-hypertensive medications, statins, and estrogen therapy. Associations of menopause with non-fatal events differed by race (p for interaction=0.03). Among white women, natural menopause (hazard ratio [HR] 0.45, 95% CI 0.31, 0.66) and surgical menopause (HR 0.65, 95% CI 0.42, 0.99) were associated with a reduced hazard of non-fatal events compared to white men. Among black women, natural menopause was marginally significantly associated with lower hazard of non-fatal events compared to men (HR 0.69, 95% CI 0.47, 1.03) but surgical menopause was not (HR 0.81, 95% CI 0.51, 1.29). For acute CHD death, women had lower risk than men regardless of their menopause type and race. Conclusions and Relevance: Sex differences in the risk of incident CHD events were larger among whites than blacks and varied by type of menopause. Women consistently had a lower risk of incident CHD death than men, but the magnitude of sex differences was greater in whites than blacks for non-fatal events regardless of menopause type. Menopause type was not associated with large differences in the hazard for CHD risk.
Endocrine Pathophysiology: A Patient-Oriented Approach.
Authors: Jerome M. Hershman
Journal: Annals of Internal Medicine (1991)

erences (to North-American and European authors!). The newest aspects and techniques are discussed, but one should bear in mind the correct attitude outlined in the foreword by Melvin R. Cohen: “The two chief indications for laparoscopy are (1) diagnosis of obscure pelvic disease, and (2) tubal sterilization. Even the experienced laparoscopist should not tackle a procedure that is better treated by laparotomy”. Gynecologists should peruse this textbook in order to gain an extensive knowledge on the potencies and hazards of laparoscopy.
Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis
Authors: Philip Washbourne, Peter M. Thompson, Mario Carta, Edmar T. Costa, James R. Mathews, Guillermina Lopez-Benditó, Zoltán Molnár, Mark W. Becher, C. Fernando Valenzuela, L. Donald Partridge, Michael C. Wilson
Journal: Nature Neuroscience (2001)