tbuckley/cabot-search huggingface dataset:
Association of activated NF-kB, altered cyclin D1 and poor outcome in esophageal adenocarcinoma
Authors: Usha Malhotra, Walter N. Hittelman, Tsung T. Wu, Rajyalashmi Luthra, Steven Swisher, Madan Luthra, Arlene Correa, Bharat B. Aggarwal, Jaffer Ajani, Julie G. Izzo
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2334 

The dramatic increased incidence and poor survival rates of esophageal adenocarcinoma (EAC) underscore the need for novel therapeutic targets. Cyclin D1 (CD1) altered protein expression has been proposed as an early predictor for malignant transformation in EAC. We previously reported that cyclin D1 A870G polymorphism, which influences CD1 protein turnover, was associated with increased CD1 levels, early onset and poor outcome in EAC. However, the upstream mechanisms of CD1 transcriptional activation in EAC are still unknown. To examine the potential role of the transcription factor NF-kappaB (NF-κB) as an upstream regulator of CD1, we compared the correlation of activated NF-κB (nuclear localization), CD1 protein expression and clinical outcome in 66 patients undergoing surgical resection for EAC. All pathological specimens contained EAC and normal squamous mucosa; 34/66 cases contained Barrett’s premalignant lesions. NF-κB positivity was found in 48/66 (72.7%) EAC, associated with concomitant CD1 overexpression in 41/48 (85.4%) cases. CD1 was overexpressed in only 1/18 NF-κB negative EAC. While NF-κB/CD1 positive and negative EAC groups showed similar frequencies of soft tissue and lymph nodes invasion [20/41 (48.7%) NF-kB/CD1 positive vs 16/25 (64%) NF-κB/CD1 negative, p=1.0], the NF-κB/CD1 positive group showed increased perineural/vascular invasion [14/41 (34%) NF-κB/CD1 positive vs 2/25 (8%) NF-κB/CD1 negative, p=.01]. The NF-κB/CD1 positive group also developed more recurrences and distant metastasis [23/41 (56%) NF-κB vs 7/25 (28%) NF-κB/CD1 negative, p=.040] and had a shortened survival ([fig.][1]). NF-κB and CD1 were concomitantly positive in 28/34 (82.3%) adjacent Barrett’s premalignant epithelia. Interestinlgy, activated NF-kB and cyclin D1 overexpression were spatially colocalized in EAC and the adjacent premalignant lesions. These results suggest that NF-kB may be involved in the transcriptional upregulation of CD1 during the progression to EAC, and may represents a novel target for the prevention and treatment of EAC. (UTMDACC Esophageal MRP, EDRN 86390)



![Figure][2]  [1]: #F1
 [2]: pending:yes
Government abused power as sole employer of junior doctors, says BMA chair
Authors: Abi Rimmer
Journal: BMJ (2016)

The government has abused its power as the sole employer of junior doctors, the BMA’s chair of council has said.

Speaking to The BMJ on the eve of the all-out strike by junior doctors on 26 April, Mark Porter said that during negotiations on the new contract for junior doctors the government had abused its position as the only employer in England that could provide specialist training.

“One of the reasons that the government is behaving the way it is, of course, [is] because the NHS is . . . a sole employer of junior doctors,” he said. “You can’t get legitimate junior doctor training anywhere else other than by going abroad.

“So, if you want to progress in specialist training you have to work for the …
Main paediatric centre in Aleppo is destroyed by airstrike
Authors: Anne Gulland
Journal: BMJ (2016)

A hospital whose facilities included the main paediatric referral centre in the Syrian city of Aleppo has been destroyed in a bomb attack, resulting in the deaths of at least 14 people, including two doctors, the medical charity Medecins Sans Frontieres (MSF) has reported.

In a statement MSF said that Al Quds Hospital was hit by at least one airstrike, reducing it to rubble.

“MSF categorically condemns this outrageous targeting of yet another medical facility in Syria,” said Muskilda Zancada, MSF’s head of mission. “This devastating attack …
Planning Low-Sodium Meals: A Community Project
Authors: Pearl A. Thoreson, Arthur D. Baldwin, Ernest M. Morris, William J. Zukel
Journal: New England Journal of Medicine (1952)

WITHIN recent years the use of low-sodium diets in the treatment of congestive heart failure has become accepted medical practice.1 Moreover, the beneficial results obtained in hypertensive patients on the Kempner rice diet have been attributed by some authorities primarily to the rigid sodium restriction of the rice diet.2 However, attempts to maintain a patient on a rice or other low-sodium diet are often discouraging for both patient and physician; hence often the full potential benefit of the diet is not attained.A study of low-sodium diets was undertaken in February, 1950, in Newton, Massachusetts, as one of the activities . . .
Soundings: She's bleeding again
Authors: James Owen Drife
Journal: BMJ (2002)

Obstetric haemorrhage is frightening, at least for the obstetrician. The woman's partner, however, views it calmly through his video camera. He knows there is always a lot of blood. When the norm is exceeded it is the professionals who sweat.

Life threatening haemorrhage occurs after one in a thousand births, so each NHS obstetrician should see a case every year or two. Not so. The play of chance means that in each hospital one consultant sees them all. The rest of us feel quietly smug, as if our good luck were of our own making. Then the wheel of fortune rotates and it's your turn.

An obstetrician's day job consists of balancing one small risk against another and trying to avoid both. Saving babies has become a matter of applying protocols. So when you help save a mother's life you feel liberated, but only briefly. Even while you are checking the drip and catheter, the partner is asking whether all this could have been prevented.

Emergencies have a way of telescoping your memory. You remember the last time and the time before that, as if they were yesterday. You hear yourself telling the trainee what the old prof did when you were a registrar. Then you realise that you are the old prof now.

These days there are courses that create the adrenaline rush under controlled conditions, so new consultants are well prepared. Still, some lessons only come through experience. Always empty your bladder, for example, and, however urgent the dash to theatre, never leave your credit cards in the changing room.

Immediately afterwards, there is a high. It has little to do with altruism. It comes from being part of a team and confronting something real. During an emergency there is no pretence. The team's rapport is instinctive. They read one another's body language. They tolerate foibles and feeble wisecracks but not indecision. And when the worst is over, they become phlegmatic.

The worst? That is when you have done everything and someone says, “She's bleeding again.” At this moment, I recommend the Tarrant manoeuvre—phone a friend. On call or not, colleagues won't mind. They will offer to come in but all you want is a reassuring voice. Believe me, it helps. Take the word of an old prof.
Sex Differences in Renal Proximal Tubular Cell Homeostasis
Authors: Thomas Seppi, Sinikka Prajczer, Maria-Magdalena Dörler, Oliver Eiter, Daniel Hekl, Meinhard Nevinny-Stickel, Iraida Skvortsova, Gerhard Gstraunthaler, Peter Lukas, Judith Lechner
Journal: Journal of the American Society of Nephrology (2016)

Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione- S -transferase– α . Additionally, we quantified urinary excretion of blood plasma proteins α 1–microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione- S -transferase– α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α 1–microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ–derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.
CD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling
Authors: Yongkang Qiao, John Kit Chung Tam, Sheryl S.L. Tan, Yee Kit Tai, Chin Yein Chin, Alastair G. Stewart, Leonie Ashman, Kiyotoshi Sekiguchi, Shenna Y. Langenbach, Gerald Stelmack, Andrew J. Halayko, Thai Tran
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 5025: Immune expression profiling of MAPK inhibitor resistant tumors based upon mechanisms of resistance
Authors: James S. Wilmott, Hojabr Kakavand, Alexander M. Menzies, Ricardo Vilain, Gulietta M. Pupo, John F. Thompson, Richard F. Kefford, Matteo S. Carlino, Helen Rizos, Georgina V. Long, Richard A. Scolyer
Journal: Cancer Research (2015)

Abstract Purpose: To evaluate the association between the immunoreactivity of the immune inhibitory ligand PD-L1 with tumour infiltrating lymphocytes (TILs) and known mechanisms of MAPK inhibitor (MAPKi) resistance in tumor biopsies resected at the time of MAPKi disease progression. Experimental Design: 23 patients with disease progression on MAPKi (vemurafenib, dabrafenib, and combination dabrafenib and trametinib) each had a progressing tumor biospied. All tumors underwent MAPKi resistance screening including RNA expression profiling. Morphological features, PD-L1 immunohistochemical immunoreactivity, and RNA expression profile were correlated with mechanisms of resistance (including mutations in NRAS and MEK, and amplification and aberrant splicing of BRAF). Results: PD-L1 immunoreactivity was significantly higher in tumors that harbored an aberrant BRAF splicing variant (n = 8) or MEK mutations (n = 5) than those with BRAF amplification (n = 4), NRAS mutations (n = 2) or those with unknown resistance mechanisms (n = 4) (mean 27% vs 1%, p = 0.049). Additionally, the PD-L1 immunoreactivity in tumors with known MAPK-reactivating mechanisms (n = 19) tended to be higher than those with unknown resistance mechanisms (n = 4) (mean 17% vs 0%, p = 0.283). The immunoreactivity of PDL1 in progressed lesions was independent of BRAFV600 genotype, RECIST response and type of MAPK inhibitor. Correlations with TIL subsets, RNA expression, and response to subsequent anti-PD-1 therapy are underway. Conclusions: The induction of PD-L1 immunoreactivity following MAPKi treatment in human melanoma is variable, however specific mechanisms of MAPKi resistance may confer increased expression of the inhibitory ligand. Further study is underway examining the association of the above with TIL infiltration, the RNA expression profile, and the response to subsequent anti-PD1 therapy. Citation Format: James S. Wilmott, Hojabr Kakavand, Alexander M. Menzies, Ricardo Vilain, Gulietta M. Pupo, John F. Thompson, Richard F. Kefford, Matteo S. Carlino, Helen Rizos, Georgina V. Long, Richard A. Scolyer. Immune expression profiling of MAPK inhibitor resistant tumors based upon mechanisms of resistance. [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 5025. doi:10.1158/1538-7445.AM2015-5025
Abstract 17609: Comparison of All-cause and Bleeding-related Hospitalizations Among Non-valvular Atrial Fibrillation Patients Receiving Oral Anticoagulants
Authors: Steve Deitelzweig, Amanda Bruno, Kiran Gupta, Jeffrey Trocio, Natalie Tate
Journal: Circulation (2015)

To compare the risk of hospitalization among non-valvular atrial fibrillation (NVAF) patients newly initiated with an oral anticoagulant (OAC): apixaban, dabigatran, rivaroxaban, or warfarin. Retrospective cohort study using Humana Medicare Advantage data from 7/1/2009 - 9/30/2014. NVAF patients ≥18 years receiving one OAC on the index date with 6 months continuous enrollment prior to index prescription date and 3 months post-index were eligible. Hospitalizations were identified by standard codes for inpatient admission. Bleeding-related hospitalizations required an additional code for major/clinically relevant non-major (CRNM) bleeding. A cox proportional hazards model was used to estimate the hazard ratios (HR) of hospitalizations adjusted for age, sex, region, comorbidities and comedications. Adherence for each OAC was also calculated using a proportion of days covered approach to understand medication taking behaviors. Among the 53,168 patients initiated on an OAC, 2,028 (3.8%) apixaban, 5,644 (10.6%) dabigatran, 7,667 (14.4%) rivaroxaban and 37,829 (71.1%) warfarin. Patients in apixaban cohort were older (mean 75.5 years, P &lt;0.05) with higher mean CHA 2 DS 2- VASc score (P &lt;0.05). Abixaban patients had a higher mean HAS-BLED score vs. dabigatran (P &lt;0.0001), lower mean score vs. warfarin (P &lt;0.0001) and did not differ significantly vs. rivaroxaban (P =0.46). Patients receiving apixaban had a significantly lower risk for all-cause hospitalization across cohorts, and a sig. lower risk for bleeding-related hospitalization vs. patients receiving rivaroxaban or warfarin (Table). Adherence ranged from 87.8% to 90.4% across cohorts. In a real-world setting, initiation with apixaban was associated with a significantly lower risk for all-cause hospitalization, and a significantly lower risk of bleeding-related hospitalization compared to rivaroxaban or warfarin. Table: Adjusted Hazard Ratios of All-cause and Bleeding-related Hospitalizations
Soundings: Good doctors doing nothing
Authors: Liam Farrell
Journal: BMJ (1999)

Gaelic football is our national game, followed fanatically in every parish in the land. The climax of the year is in Croke Park in September, the All Ireland final, and exiles from all across the world tune in to feel the pulse of the heartland. The game is started by throwing in the ball; this function used to be performed by the Archbishop of Dublin, who would then have to hitch his skirts up and scurry off the field in case he interfered with play.

Though this farcical demonstration of ecclesiastical hegemony has disappeared, another reminder of its sinister consequences endures. The Artane Boys Band has long been a tradition of this great day, a jolly bunch of ostensibly happy, fresh faced urchins leading the teams round the field beforehand and entertaining the crowds at half time.

But a recent television documentary, States of Fear, has exposed how generations of vulnerable children have been ill treated and abused by the Catholic church and its institutions. These were not charitable institutions; the state paid the church well for this trust and then looked the other way as it was violated.

Artane was an industrial school, run by the Christian Brothers. One musical director of the band was much feted in his day, even to having a hagiographical television special programme made— compulsive if loathsome viewing. He has since been unveiled as a serial child molester.

Artane was not an isolated case. There are a myriad other stories, all of them distressing and many of them very recent. But where were the doctors when all this was happening? At some stage many doctors must have seen the damage: injuries, neglect, and sexual abuse; but the frightened children who needed help were betrayed, and when we hear more horror stories we should think of the many seemingly good doctors who stood idly by.

I am ashamed of the silence of my profession, but it must be hard to stand alone against the establishment, especially because as doctors we are a part of it, and perhaps we need some form of medical watchdog group to which we could confidentially report any suspicions. The potential for abuse of vulnerable children remains, and for evil to prosper, good men need only to continue to do nothing.
In-vitro effects of pemetrexed on bronchioloalveolar and adenocarcinoma of the lung
Authors: Sean Tracy, Bruce E. Johnson, Pasi A. Jänne
Journal: Cancer Research (2005)

5864  Pemetrexed disodium (ALIMTA®, LY231514; Eli Lilly & Company, Indianapolis, IN, USA) is an antimetabolite that targets folate-requiring enzymes in the pyrimidine and purine synthesis pathways. Pemetrexed is an effective drug against mesothelioma, a cancer characterized by high levels of mRNA expression and protein production of the alpha folate receptor. mRNA microarray expression results of different types of lung cancers were evaluated to determine which histological types had high levels of alpha folate receptor and similar expression patterns of folate metabolism genes as mesothelioma. The expression patterns were studied to attempt to identify subsets of lung cancers which might respond more frequently to pemetrexed. The expression of the alpha folate receptor is 2.0 times higher in bronchioloalveolar carcinomas than mesotheliomas (p = 0.002), and 2.6 times that of other adenocarcinomas (p
Allergic Bronchial Asthma and Pulmonary Infection Due to Aspergillus Fumigatus Treated by Injections of Emulsified Allergen
Authors: J W ARGABRITE, M B MORROW, G H MEYER
Journal: JAMA (1963)

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
Case 31-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, B.W. Levine, E.J. Mark
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 42-year-old woman was admitted to the hospital because of increasing dyspnea and a cough.The patient was a native of the Cape Verde Islands and spoke only Portuguese. Three months before admission she came to this country to visit relatives. Since that time she had been admitted on two occasions to the gynecology service of another hospital because of pelvic pain and weight loss; details of the findings and treatment at the other hospital were unobtainable. During the two or three months before entry she had a chronic cough. On the second entry to the other . . .
MENA Promotes Tumor-Intrinsic Metastasis through ECM Remodeling and Haptotaxis
Authors: Miguel Santiago-Medina, Jing Yang
Journal: Cancer Discovery (2016)

Oudin and colleagues report a novel and specific function of MENA in mediating directional migration of breast cancer cells toward a fibronectin gradient of increasing concentration. This MENA-mediated haptotactic response depends on the binding of MENA to the α5β1 integrin receptor, adhesion protein signaling, and fibronectin fibrillogenesis. Cancer Discov; 6(5); 474-6. ©2016 AACRSee related article by Oudin et al., p. 516.
Mediterranean diet reduces cardiovascular events in people with heart disease, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Although eating a Mediterranean diet high in vegetables, fruit, fish, and whole grains is associated with a lower risk of cardiovascular events in people with stable coronary heart disease, eating a Western-style diet does not increase this risk, a large follow-up study has shown.1

The study included 15 482 people (mean age 67) with stable coronary heart disease from 39 countries around the world. Participants completed a lifestyle questionnaire at baseline that included questions about the foods they …
Second Umbilical Cord Blood Transplant (UCBT2) In Adult Patients With Engraftment Failure Or Autologous Hematopoiesis After UCBT
Authors: Paolo F. Caimi, Ronald Sobecks, Pingfu Fu, Brenda W Cooper, Erica L. Campagnaro, Basem M. William, Rolla Abu-Arja, Merle J. Kolk, Richard J Creger, Hien Kim Duong, Brian T. Hill, Brian J. Bolwell, Matt Kalaycio, Marcos de Lima, Hillard M. Lazarus
Journal: Blood (2013)
Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain
Authors: Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, NiCole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray
Journal: Molecular Neurodegeneration (2016)

Biological pathways that significantly contribute to sporadic Alzheimer's disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes. To access this information we probed relative levels of close to 600 secreted signaling proteins from patients' blood samples using antibody microarrays and mapped disease-specific molecular networks. Using these networks as seeds we then employed independent genome and transcriptome data sets to corroborate potential pathogenic pathways. We identified Growth-Differentiation Factor (GDF) signaling as a novel Alzheimer's disease-relevant pathway supported by in vivo and in vitro follow-up experiments, demonstrating the existence of a highly informative link between cellular pathology and changes in circulatory signaling proteins.
Immune Reconstitution in Recipients of Living Donor Kidney/Hematopoietic Stem + Facilitating Cell Transplants
Authors: Joseph R. Leventhal, Mary J Elliott, Esma S. Yolcu, Larry D. Bozulic, David J Tollerud, James M Mathew, Iwona M Konieczna, Michael G Ison, Mark Badder, Michael M I Abecassis, Joshua Miller, Suzanne T. Ildstad
Journal: Blood (2014)