tbuckley/cabot-search huggingface dataset:
Keeping track of AID
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

A DNA-mutating enzyme that fine-tunes B cell antibody specificity can become a dangerous liability if its activity is mistimed, misplaced, or left unchecked. Crouch et al. (page 1145) have now designed a mouse model to track the enzyme's activity in B cells during development and immunity. The model can now be used to determine how the enzyme's destructive force is controlled.






Figure 1

Permanently marking B cells that have AID activity with YFP (green) shows that AID is turned on upon B cell activation.




The enzyme in question is AID (activation-induced cytidine deaminase), which converts cytidines to uracils. AID activity within activated B cells allows them to better recognize a pathogen by creating mutations in the variable regions of their immunoglobulin (Ig) genes. AID-assisted recombination within Ig constant regions also allows B cells to generate different types of antibodies. Mismatch repair mechanisms then splice out the mutations, reseal the new ends, and thereby create new sequence variants at the Ig loci. But this AID clean-up machinery is itself error-prone and increases the likelihood of further mutations that make the animal vulnerable to diseases such as cancer.

To monitor the expression of AID in vivo, the team designed transgenic mice that express a fluorescent protein upon AID activation that then permanently marks all AID-expressing cells and their progeny. AID, the team found, was not expressed by developing B cells. It was first switched on in activated B cells that were beginning to proliferate in germinal centers (GC)—the hub of the B cell immune response.

The switch seems to be controlled by a short DNA sequence immediately downstream of the AID gene. This sequence had more histone acetylation (which marks transcriptionally active regions) in activated B cells. Deleting the sequence almost completely abolished AID expression.

AID expression was down-regulated as B cells differentiated into either memory cells or antibody-producing plasma cells and began to leave the GC. The exact mechanism that shuts off AID in exiting B cells remains to be worked out. Using this model to resolve this mechanism and understand how AID regulatory mechanisms get derailed in B cell cancers is the team's next step.
The Frey Procedure for Chronic Pancreatitis Secondary to Pancreas Divisum
Authors: Sam G. Pappas, Charles H. C. Pilgrim, Rebecca Keim, Rachel Harris, Stuart Wilson, Kiran Turaga, Susan Tsai, Kulwinder Dua, Abdul Khan, Young Oh, T. Clark Gamblin, Kathleen Christians
Journal: JAMA Surgery (2013)

Pancreas divisum is an uncommon congenital anomaly that may result in chronic pancreatitis (chronic pancreatitis secondary to pancreas divisum [CPPD]) and intractable pain. We evaluated the role of the Frey procedure in the management of patients with pain related to CPPD as compared with patients with chronic pancreatitis secondary to alcohol (CPA) or idiopathic causes (ICP).To review our experience with the Frey procedure for the management of chronic pancreatitis related to pancreas divisum.This was a 2-year institutional retrospective of patients undergoing the Frey procedure for chronic pancreatitis related-pain from April 2008 to June 2010.Academic tertiary care referral center.A consecutive sample of 14 patients undergoing the Frey procedure for chronic pancreatitis and disease-related intractable pain. We sought to examine the utility of the Frey procedure in patients with CPPD as compared with CPA and ICP.The Frey procedure.Perioperative outcomes and postoperative narcotic requirement were compared among patient groups.Fourteen patients underwent the Frey procedure. The etiology of the disease was pancreas divisum in 6 patients, alcohol in 5, and idiopathic in 3. The most common indication for surgery was intractable pain, and all patients had undergone endoscopic retrograde cholangiopancreatography for attempted relief in the past. There were no statistically significant differences in median operative time (263 minutes), intraoperative blood loss (425 mL), median length of stay (9.5 days), or rate of morbidity (21%) between the 3 etiologies. Two-thirds of patients required less or no opioid at follow-up, although follow-up was significantly longer for CPPD and ICP than CPA (median, 249, 259, and 42 days, respectively; P < .02).In this series, outcomes for patients with CPPD treated with the Frey procedure were equivalent to those treated for CPA. Patients with pancreas divisum and a dilated pancreatic duct may be ideally suited for this surgical strategy. The potential advantage of this approach over minor duct sphincteroplasty and lateral pancreaticojejunostomy is the removal of the fibrotic tissue of the head of the pancreas, thought to be the epicenter of pain in this condition. The benefits over resection alone include a more extensive ductal drainage procedure.
Mineralocorticoid Receptor Inhibition Ameliorates the Transition to Myocardial Failure and Decreases Oxidative Stress and Inflammation in Mice With Chronic Pressure Overload
Authors: Gabriela M. Kuster, Eugene Kotlyar, Mary K. Rude, Deborah A. Siwik, Ronglih Liao, Wilson S. Colucci, Flora Sam
Journal: Circulation (2005)

Background— Although aldosterone, acting via mineralocorticoid receptors, causes left ventricular (LV) hypertrophy in experimental models of high-aldosterone hypertension, little is known about the role of aldosterone or mineralocorticoid receptors in mediating adverse remodeling in response to chronic pressure overload. Methods and Results— We used the mineralocorticoid receptor–selective antagonist eplerenone (EPL) to test the role of mineralocorticoid receptors in mediating the transition from hypertrophy to failure in mice with chronic pressure overload caused by ascending aortic constriction (AAC). One week after AAC, mice were randomized to regular chow or chow containing EPL (200 mg/kg per day) for an additional 7 weeks. EPL had no significant effect on systolic blood pressure after AAC. Eight weeks after AAC, EPL treatment improved survival (94% versus 65%), attenuated the increases in LV end-diastolic (3.4±0.1 versus 3.7±0.1 mm) and end-systolic (2.0±0.1 versus 2.5±0.2 mm) dimensions, and ameliorated the decrease in fractional shortening (42±2% versus 34±4%). EPL also decreased myocardial fibrosis, myocyte apoptosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2. These beneficial effects of EPL were associated with less myocardial oxidative stress, as assessed by 3-nitrotyrosine staining, reduced expression of the adhesion molecule intercellular adhesion molecule-1, and reduced infiltration by macrophages. Conclusions— Mineralocorticoid receptors play an important role in mediating the transition from LV hypertrophy to failure with chronic pressure overload. The effects of mineralocorticoid receptor stimulation are associated with alterations in the interstitial matrix and myocyte apoptosis and may be mediated, at least in part, by oxidative stress and inflammation.
THE THERAPEUTIC PROPERTIES OF THE SUPRARENAL CAPSULE.
Authors: W. H. BATES
Journal: JAMA (1900)

The curative action of the suprarenal extract, dealing with all inflammations of the body and with those diseases which are affected by changes in blood-pressure, covers a wide area of therapeutic application. If we are to use this drug, which is so rapid that its maximum effect is reached in less than one minute, and so potent that some obstinate cases of chronic keratitis have been cured in one treatment, it is imperative that we should know what effect the suprarenal extract, absorbed from its local use in the eye or ear, will have on other organs, since the patient may also have serious lesions of the heart, kidneys or other tissue. To obtain this necessary knowledge, I had at my command my own clinical observations, my laboratory experiments, and the experiences of physicians whose work lies in other fields. The conclusion drawn from these data is that no condition
348 HOMODIMERIZATION OF THE HEPATITIS C VIRUS NON-STRUCTURAL 4B PROTEIN REQUIRES AN INTACT BASIC LEUCINE ZIPPER
Authors: M.W. Welker, C. Welsch, A.K. Meyer, N. Forestier, B. Kronenberger, T. Lengauer, A. Piiper, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2009)
Cancer of the Oesophagus - Palliation - Laser Treatment and Combined Procedures
Authors: R. R. Sander, H. Poesl
Journal: Endoscopy (1993)

Today, laser photodestruction is a low-risk, easily applied standard procedure for the palliation of malignant stenoses of the oesophagus, the aim of which is to recanalize the stenosis and improve the patient's quality of life. This is confirmed by our own experience in 130 patients, in 96% of whom recanalization proved successful and reproducible at any time. Complications requiring treatment were seen in less than 10% of the cases, and all responded to conservative therapy; only one patient died. In patients with squamous cell carcinoma, the use of complementary measures possibly results in a limited prolongation of survival. Photodynamic therapy offers further possibilities, although its clinical use in gastroenterology is presently restricted to early superficial tumours.
Pheochromocytoma Without Hypertension
Authors: Marcel T. Kahn, David A. Mullon
Journal: JAMA (1964)

IN 1950, almost 30 years after the first description of pheochromocytoma, Smithwick<sup>1</sup>was able to collect only 270 cases from the literature. Since then an ever increasing number of cases has been reported, indicating a growing awareness of this disease. Many excellent reviews have pointed out the diagnostic difficulties so frequently encountered. A case of pheochromocytoma recently observed in a patient with chronic acromegaly should serve to demonstrate a few of these diagnostic difficulties. In addition, the combination of pheochromocytoma with chronic pituitary adenoma may stimulate some etiological considerations. <h3>Report of a Case</h3> In 1944, a 23-year-old white male developed signs and symptoms of acromegaly. In 1945, enlargement and erosion of the sella turcica were noted on x-rays, characteristic visual field defects were found, and the patient received radiation therapy for a pituitary adenoma. Thirteen years later, in April and in June, 1960, he had two brief episodes of
Genomic analysis of the role of transcription factor C/EBPδ in the regulation of cell behaviour on nanometric grooves
Authors: Jolanta Wiejak, Penelope M. Tsimbouri, Pawel Herzyk, Matthew J. Dalby, Graham Hamilton, Stephen J. Yarwood
Journal: Biomaterials (2012)

C/EBPδ is a tumour suppressor transcription factor that induces gene expression involved in suppressing cell migration. Here we investigate whether C/EBPδ-dependent gene expression also affects cell responses to nanometric topology. We found that ablation of the C/EBPδ gene in mouse embryonal fibroblasts (MEFs) decreased cell size, adhesion and cytoskeleton spreading on 240 nm and 540 nm nanometric grooves. ChIP-SEQ and cDNA microarray analyses demonstrated that many binding sites for C/EBPδ, and the closely related C/EBPβ, exist throughout the mouse genome and control the upregulation or downregulation of many adjacent genes. We also identified a group of C/EBPδ-dependent, trans-regulated genes, whose promoters contained no C/EBPδ binding sites and yet their activity was regulated in a C/EBPδ-dependent manner. These genes include signalling molecules (e.g. SOCS3), cytoskeletal components (Tubb2, Krt16 and Krt20) and cytoskeletal regulators (ArhGEF33 and Rnd3) and are possibly regulated by cis-regulated diffusible mediators, such as IL6. Of particular note, SOCS3 was shown to be absolutely required for efficient cell spreading and contact guidance on 240 nm and 540 nm nanometric grooves. C/EBPδ is therefore involved in the complex regulation of multiple genes, including cytoskeletal components and signalling mediators, which influence the nature of cell interactions with nanometric topology.
Bilateral Retinoblastoma: A Dominantly Inherited Affection
Authors: A. Sorsby
Journal: BMJ (1972)

Ten survivors of sporadic bilateral retinoblastoma had 14 offspring, of whom eight were affected, seven of them in both eyes. Other reports from the literature raise the total of similar unselected cases to 19 survivors with a total of 39 offspring, of whom 17 were affected in both eyes and three in one eye.The high incidence of the bilateral affection in dominantly inherited retinoblastoma-as recorded in the literature-and in the offspring of survivors from sporadic bilateral retinoblastoma, as reported in the present study, establish all cases of bilateral retinoblastoma as a dominant disorder either in transmission or as a new mutation. This disorder, though fully or almost fully penetrant, is not always fully expressed. A small proportion, probably about 5 to 10% of all cases of the much more common sporadic unilateral affection, are in fact incompletely expressed germinal mutations for bilateral retinoblastoma. There is some evidence that histological appearances may distinguish these potentially transmissible unilateral tumours from the mass of unilateral retinoblastoma which have no genetic significance.
High Court rejects overseas doctors' challenge of UK work restrictions
Authors: Clare Dyer
Journal: BMJ (2007)

Doctors from other countries who challenged the UK government in the High Court over new rules restricting their right to work in Britain lost their case last week.

Mr Justice Stanley Burnton ruled that the government had acted lawfully when it abolished the permit free training scheme, which allowed graduates of foreign medical schools outside the European Union to take up training posts in the United Kingdom without a work permit.

He also upheld guidance from the Department of Health that has made it much harder for doctors on the highly skilled migrant programme to obtain appointments in the NHS.

The British Association of Physicians of Indian Origin, which brought the challenge, was given permission to now take its case to the Court of Appeal. Ramesh Mehta, …
Abstract S4-9: Comparing the Prediction of Chemotherapy Benefit in Patients with Node-Negative, ER-Positive Breast Cancer Using the Recurrence Score and a New Measure That Integrates Clinical and Pathologic Factors with the Recurrence Score
Authors: G Tang, JP Costantino, M Crager, S Shak, N. Wolmark
Journal: Cancer Research (2010)

Abstract Background: The 21-gene Oncotype DX® Recurrence Score® (RS) is widely used for assessment of recurrence risk and prediction of chemotherapy benefit in patients with early stage ER-positive breast cancer. Through a meta-analysis on the NSABP B-14 study and the ATAC study, the Recurrence Score-Pathology-Clinical (RSPC) risk assessment has been developed as an integration of RS and clinico-pathologic factors (including tumor size, tumor grade and age) for assessment of recurrence risk in early stage ER-positive, node-negative breast cancer. The value of RSPC in prediction of chemotherapy benefit needs to be evaluated. Methods: In the NSABP trial B-20, patients were node-negative and ERpositive by the ligand binding assay, and were randomized to tamoxifen with or without adjuvant chemotherapy (MF or CMF). B-20 patients who had successful Oncotype DX RS assay and ER score ≥6.5 were included in this study. Cox proportional hazards models with interaction terms were used to evaluate RS and RSPC in prediction of chemotherapy benefit in reducing risk of distant recurrence. Results: The analysis included 625 patients among whom 60 distant recurrence events occurred. RS showed a significant interaction with chemotherapy treatment (p=0.037), as found previously, with a standardized hazard ratio (HR) of 0.836. The interaction of RSPC with treatment was not significant (p=0.10), although the trend was in the same direction as RS (standardized HR 0.833). Conclusions: RS used alone remains the best predictor of chemotherapy benefit in ER-positive, node-negative breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-9.
Acute-Onset Floaters and Flashes and Risk for Retinal Detachment
Authors: Joel Porter
Journal: JAMA (2010)

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
Colorectal Cancer Screening
Authors: S. Bharath
Journal: JAMA (1979)

To the Editor.—  In a recent letter M. J. Goodman, MD (240:2733, 1978), reported 6.8% positive tests for occult blood, using the mail-in Hemoccult (HO) II slides rehydrated before adding the testing reagent, in his colorectal cancer screening study of patients older than 45 years. Winawer et al have presented the following facts in Progress Report on Controlled Trial of Fecal Occult Blood Testing for the Detection of Colorectal Neoplasia at the recent American College of Gastroenterology 43rd Annual Convention: The initial HO slide resulted in a 1% positive rate, with a 50% predictive value for neoplastic lesions in patients screened positive and a false-positivity of 0.5%. The new HO II slide was more sensitive, with a positive rate of 3.7% having a predictive value of 44% and a false-positivity of 2.1%. The HO II slide with rehydration resulted in a positive rate of 5.3%, having a predictive value of
Hospitals' star ratings and clinical outcomes: ecological study
Authors: Kathy Rowan, David Harrison, Anthony Brady, Nick Black
Journal: BMJ (2004)

The English Department of Health is developing global measures of the performance of all NHS bodies, including 166 acute hospital trusts. Since 2000-1, the trusts get zero, one, two, or three stars to indicate performance.1 This rating may not reflect the effectiveness of clinical care measured in patient outcomes because of the lack of accurate routine data.2 One exception is in adult critical care3; we checked whether a hospital's rating provided an indication of its clinical outcomes.

We compared the 2001-2 rating of 102 acute hospital trusts for which we had validated data for that year. We calculated each patient's predicted risk of death before discharge from hospital4 and compared it with actual mortality for all admissions in 2001-2 for each unit.

We compared rating with crude mortality at the patient level rather than aggregated by hospital; our sample …
Antiangiogenic-targeting drug-loaded microbubbles combined with focused ultrasound for glioma treatment
Authors: Ching-Hsiang Fan, Chien-Yu Ting, Hao-Li Liu, Chiung-Yin Huang, Han-Yi Hsieh, Tzu-Chen Yen, Kuo-Chen Wei, Chih-Kuang Yeh
Journal: Biomaterials (2012)
The Effect of Penicillin on Inoculation Malaria
Authors: J. A. Hindle, A. S. Rose, L. D. Trevett, C. Prout
Journal: New England Journal of Medicine (1945)

UNDER a well-organized national program, clinical and laboratory data showing the therapeutic effectiveness of penicillin in many disease conditions are rapidly accumulating. Recently penicillin has been made available for more widespread civilian use in certain specified infections. There are few factual data available concerning its efficacy in malaria.Relapsing tertian malaria in many of the returning troops is proving a definite problem. The chief concern is about the best method for the active treatment of these relapses and about the possibility that such malarial infestations will form a reservoir for a marked increase in cases among the general population. It . . .
INVOLUNTARY DYEING OF THE HAIR. CLINICAL NOTE. INVOLUNTARY DYEING OF THE HAIR
Authors: A. M. H. GRAY, ROBERT KLABER
Journal: British Journal of Dermatology (1936)

Journal Article INVOLUNTARY DYEING OF THE HAIR. CLINICAL NOTE. INVOLUNTARY DYEING OF THE HAIR Get access A. M. H. GRAY, M.D., F.R.C.P., A. M. H. GRAY, M.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar ROBERT KLABER, M.D., M.R.C.P. ROBERT KLABER, M.D., M.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 48, Issue 2, 1 February 1936, Pages 97–99, https://doi.org/10.1111/j.1365-2133.1936.tb10306.x Published: 01 February 1936
Obituaries: the future
Authors: S. Lock, R. Smith
Journal: BMJ (1995)

Developing by evolution not revolution

Obituaries are one of the most popular sections of the BMJ. The many letters that we received in response to our last editorial on obituaries and the high response rate to our questionnaire on the subject confirmed their popularity.1 2 The letters and the answers to the questionnaire have helped us consider how to respond to the central problem: how to publish rapidly in a limited number of pages an ever increasing number of obituaries, preserving their accuracy and usefulness and increasing their readability. We think that we can achieve this through evolution rather than revolution.

Many diverse opinions were expressed by our 110 correspondents and 646 respondents to our survey sent to 1070 doctors, but some things emerged very clearly: most readers want obituaries kept, almost all were keen that we keep space for “ordinary” doctors, and a third wanted more attention paid to the subjects' failings. Consistently respondents thought that shorter obituaries would be better, and they strongly preferred a single paragraph: many would also accept, however, that the …
New study reports that diet is critical to cancer prevention
Authors: C. White
Journal: BMJ (1997)

A predominantly plant based diet and maintenance of a healthy body weight could prevent four million cases of cancer worldwide, concludes a report by the World Cancer Research Fund. A separate British report, Nutritional Aspects of the Development of Cancer , to be published shortly by the Committee on the Medical Aspects of Food and Nutrition Policy, includes similar recommendations.

In 1996 the global incidence of cancer stood at 10.3 million cases; on the basis of current trends, this is expected to reach 14.7 million cases by 2020, says the fund's report, …