tbuckley/cabot-search huggingface dataset:
A link between c-Myc-mediated transcriptional repression and neoplastic transformation.
Authors: L A Lee, C Dolde, J Barrett, C S Wu, C V Dang
Journal: Journal of Clinical Investigation (1996)

Recent studies indicate that the transcription factor c-Myc contributes to oncogenesis by altering the expression of genes involved in cell proliferation, but its precise function in neoplasia remains ambiguous. The ability of c-Myc to bind the sequence CAC(G/A)TG and transactivate appears to be linked to its transforming activity; however, c-Myc also represses transcription in vitro through a pyrimidine-rich cis element termed the initiator (Inr). In transfection experiments using the adenoviral major late (adML) promoter, which contains two Myc binding sites and an Inr, we determined that c-Myc represses transcription through the initiator in vivo. This activity requires the dimerization domain and amino acids 106 to 143, which are located within the transactivation domain and are necessary for neoplastic transformation. We studied a lymphoma-derived c-Myc substitution mutation at 115-Phe, which is within the region required for transcriptional suppression, and found the mutant more effective than wild-type c-Myc in transforming rodent fibroblasts and in suppressing the adML promoter. Our studies of both loss-of-function and gain-of-function c-Myc mutations suggest a link between c-Myc-mediated neoplastic transformation and transcriptional repression through the Inr.
Clinical Efficacy and Predictive Molecular Markers of Neoadjuvant Gemcitabine and Pemetrexed in Resectable Non-small Cell Lung Cancer
Authors: Gerold Bepler, K Eric Sommers, Alan Cantor, Xueli Li, Anupama Sharma, Charles Williams, Alberto Chiappori, Eric Haura, Scott Antonia, Tawee Tanvetyanon, George Simon, Coleman Obasaju, Lary A. Robinson
Journal: Journal of Thoracic Oncology (2008)
Scintigraphy in Traumatic Lesions of Liver and Spleen
Authors: George W. Evans
Journal: JAMA (1972)

Simultaneous splenic and hepatic scintigrams were performed with technetium Tc 99m colloid on 19 patients who had sustained abdominal trauma. Five cases of splenic hematoma were diagnosed; all were confirmed and successfully treated. Three cases of liver hematoma were diagnosed; two were confirmed, and all were successfully managed. There is no evidence that the procedure failed to detect clinically significant lesions of the liver or the spleen.
HYGIENE OF THE EYE.
Authors: CLARENCE R. DUFOUR
Journal: JAMA (1896)

The many cases seen in private and hospital work, which earlier could have been more effectively treated, if not entirely cured or corrected, and the earnest desire to obtain the coöperation of the general physician is my only excuse for bringing this subject before this society. As a rule, healthy parents beget healthy offspring; therefore, that the eyes may be free from disease and have perfect vision, the parents should live such lives as will conduce to health, that their children may be perfect physically and mentally; there should be legislation preventing marriage and intermarriage between those suffering from disease that may be transmitted to their children. The disastrous effect upon the eyes by syphilitic heredity is well known, also that of consanguinous marriages; in the first class we find various inflammatory conditions of retina, choroid and cornea; in the latter class we frequently find retinitis pigmentosa and sequelæ. One
A comparison of the acute effects of radiation therapy, including or excluding the thymus, on the lymphocyte subpopulations of cancer patients.
Authors: J A Stratton, P E Byfield, J E Byfield, R C Small, J Benfield, Y Pilch
Journal: Journal of Clinical Investigation (1975)

Radiation therapy to either mediastinum or pelvis causes a rapid decrease in circulating lymphocytes of both B and T types and in addition an impairment in the function of the remaining lyphocytes, as measured by their ability to proliferate in response to mitogens. The acute depression is short-lived. Substantial recovery is apparent within 3 wk after cessation of therapy; however, most patients show a modest, chronic depression in both numbers and functional capacities of circulating lymphocytes. T cells are somewhat more sensitive than B cells, but both are affected. Irradiation of the thymus per se seems to have little influence on the acute changes which occur, as patients receiving pelvic and mediastinal (including thymic) radiotherapy show a similiar degree of lymphopenia and depression of lymphocyte responsiveness.
Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study)
Authors: Peter H. Whincup, Claire M. Nightingale, Christopher G. Owen, Alicja R. Rudnicka, Ian Gibb, Catherine M. McKay, Angela S. Donin, Naveed Sattar, K. George M. M. Alberti, Derek G. Cook
Journal: PLoS Medicine (2010)

Background Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood. Methods and Findings We performed a cross-sectional survey of 4,796 children aged 9–10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference −2.9, 95% CI −4.5 to −1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased. Conclusions Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention. Please see later in the article for the Editors' Summary
Best research: New strategy is warmly welcomed
Authors: Robert Boyd, Mike Burrows
Journal: BMJ (2006)

Case reports of suspected adverse drug reactions Case reports were dismissed too quicklyEditor-The main difference between the replications by Loke et al of Venning's studies from the 1980s and the original is the evidence that is accepted as further follow-up. 1 Loke et al mention that 56 of 63 case reports on adverse reactions were cited at least once but accept only nine instances as valid follow-up: attempts at proof of mechanisms or controlled studies.However, unexpected adverse effects are by definition due to an unknown mechanism, and many established adverse effects still escape elucidation after years.Moreover, further accumulation of anecdotal reports can be sufficient evidence.A 10 year tally of 22 drugs that were withdrawn from the market showed that 18 were prompted by case reports and only four by a controlled study; for at least 13 the case reports proved sufficient reason for withdrawal. 2 A highly unusual event that is repeatedly reported in a recently marketed drug, in the absence of publicity, points to an exceedingly high relative risk, a good argument for cause and effect. 3 Moreover, these risks will be picked up spontaneously. 4 5 Apart from the nine instances of follow-up that were accepted by Loke et al, 15 datasheets were amended and seven BNP drug monographs changed.So, even with some overlap, close to half of the case reports were somehow sufficiently noteworthy to have had consequences.Given the small sample size, this is not far from Venning's original.It is a pity that Loke et al do not make all follow-up more explicit for all 56 instances that followed the 63 reports.Their overall conclusion that lack of follow-up means that case reports are of limited value is a non-sequitur.It shows that a more consistent scheme of hypothesistesting studies by industry, government, or third parties is needed instead of the current haphazard approach to drug safety.Such publications may alert and help clinicians in recognising potential adverse events in their patients.Often there is no other way of discovering something unusual.The record of systematic-that is, controlledpostmarketing surveillance in detecting unexpected adverse effects remains surprisingly poor.
Treatment of HCV infection in patients with advanced cirrhosis
Authors: Xavier Forns, Miquel Navasa, Juan Rodés
Journal: Hepatology (2004)

To the Editor: The recent AASLD Practice Guideline on Diagnosis, Management, and Treatment of Hepatitis C dealt with the topic of antiviral therapy in patients with decompensated cirrhosis. In their recommendations, Strader et al.1 suggest that antiviral therapy might be initiated at low dose in hepatitis C virus (HCV)-infected patients with mild degrees of hepatic compromise, preferably in patients who have been accepted as candidates for liver transplantation. This recommendation is essentially based on the data reported by Everson et al. after treatment of 102 cirrhotic patients awaiting liver transplantation.2 We recently analyzed the safety and efficacy of antiviral treatment in a cohort of 30 HCV-infected patients awaiting liver transplantation.3 Half of these patients had compensated cirrhosis and hepatocellular carcinoma, whereas the other half had Child-Pugh B or C cirrhosis. Our approach was completely different from that of Everson et al.: We initiated treatment (interferon alfa-2b, 3 MU/day; ribavirin, 800 mg/day) when the expected time for liver transplantation was around 4 months. Our rationale to initiate treatment when patients approached transplantation was the assumption that most virological responders would achieve HCV-RNA negativization by week 12. This strategy might be sufficient to prevent infection of the graft in these patients, since the main source of virions (the liver) will be removed. In addition, this strategy would avoid a long treatment course in patients prone to develop severe side effects. Interferon was administered daily to avoid peaks and valleys of serum interferon concentrations, which might be crucial at the time of liver transplantation. Although pegylated interferon would have been an alternative, we were afraid of a longer duration of hematological side effects in patients waiting for a major surgical procedure. After a median treatment duration of 12 weeks, 9 (30%) of 30 patients achieved on-treatment virological response, which persisted in 6 (20%) after transplantation. Although based on a small number of patients, our results are comparable to those obtained by Everson et al. In fact, we believe that a short course of antiviral therapy might be a good alternative to treat HCV-infected patients with advanced cirrhosis when the date of transplantation is known (living donor liver transplantation), or in transplant programs where the waiting time can be predicted with reasonable accuracy. Xavier Forns M.D.*, Miquel Navasa M.D.*, Juan Rodés M.D.*, * Liver Unit, Hospital Clínic, Barcelona, Spain.
Pocket Proteins Suppress Head and Neck Cancer
Authors: Myeong-Kyun Shin, Henry C. Pitot, Paul F. Lambert
Journal: Cancer Research (2012)

Head and neck squamous cell carcinomas (HNSCC) is a common cancer in humans long known to be caused by tobacco and alcohol use, but now an increasing percentage of HNSCC is recognized to be caused by the same human papillomaviruses (HPV) that cause cervical and other anogenital cancers. HPV-positive HNSCCs differ remarkably from HPV-negative HNSCCs in their clinical response and molecular properties. From studies in mice, we know that E7 is the dominant HPV oncoprotein in head and neck cancer. E7 is best known for its ability to inactivate pRb, the product of the retinoblastoma tumor susceptibility gene. However, loss of pRb function does not fully account for potency of E7 in causing head and neck cancer. In this study, we characterized the cancer susceptibility of mice deficient in the expression of pRb and either of two related "pocket" proteins, p107 and p130, that are also inactivated by E7. pRb/p107-deficient mice developed head and neck cancer as frequently as do HPV-16 E7 transgenic mice. The head and neck epithelia of the pRb/p107-deficient mice also displayed the same acute phenotypes and biomarker readouts as observed in the epithelia of E7 transgenic mice. Mice deficient for pRb and p130 in their head and neck epithelia showed intermediate acute and tumor phenotypes. We conclude that pRb and p107 act together to efficiently suppress head and neck cancer and are, therefore, highly relevant targets of HPV-16 E7 in its contribution to HPV-positive HNSCC.
Angiogenesis in Hodgkin's lymphoma: a morphometric approach in 286 patients with prognostic implications
Authors: P Korkolopoulou, I Thymara, N Kavantzas, T P Vassilakopoulos, M K Angelopoulou, S I Kokoris, E M Dimitriadou, M P Siakantaris, K Anargyrou, P Panayiotidis, A Tsenga, A Androulaki, I A Doussis-Anagnostopoulou, E Patsouris, G A Pangalis
Journal: Leukemia (2005)
If belief is a behavior, what controls it?
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (1997)

“Self-deception” usually occurs when a false belief would be more rewarding than an objective belief in the short run, but less rewarding in the long run. Given hyperbolic discounting of delayed events, people will be motivated in their long-range interest to create self-enforcing rules for testing reality, and in their long-range interest to evade these rules. Self-deception, then, resembles interpersonal deception in being an evasion of rules, but differs in being a product of intertemporal conflict.
A review of general practice reports: the need for standardisation.
Authors: J Wilton
Journal: BMJ (1990)

Fifty general practice annual reports were reviewed with a checklist to determine how much information was commonly included and whether they described the patients, the practice, and practice activity. The reports varied widely: important information was sometimes missing, practice activity was measured in different ways, and terms were often not defined. About half the reports reviewed did not draw conclusions or suggest plans for the future. Annual reports should include comparable basic information about patients, the practice, and the practice activity to optimise their usefulness in evaluation, planning, and decision making. Many relevant data are available from family practitioner committees and district health authorities.
Opportunities for Medical Research in the 21st Century
Authors: David G. Nathan, Phil B. Fontanarosa, Jean D. Wilson
Journal: JAMA (2001)

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
Coexistence of Adolescent and Adult Hospital Units: Organizational Problems
Authors: IVAN FRAS, M. ROBERT WILSON
Journal: American Journal of Psychiatry (1968)

Weekly sessions with the chief resident in child and adolescent psychiatry provided direct communication between medical and paramedical staff in an adolescent psychiatric unit organized within the adult psychiatric ward of a general hospital. These sessions ameliorated problems arising from identification of the paramedical staff with the adolescents and the staff's reaction to threatened loss of fulfillment at work.
IL-7 promotes T cell proliferation through destabilization of p27Kip1
Authors: Wen Qing Li, Qiong Jiang, Eiman Aleem, Philipp Kaldis, Annette R. Khaled, Scott K. Durum
Journal: The Journal of Experimental Medicine (2006)

Interleukin (IL)-7 is required for survival and homeostatic proliferation of T lymphocytes. The survival effect of IL-7 is primarily through regulation of Bcl-2 family members; however, the proliferative mechanism is unclear. It has not been determined whether the IL-7 receptor actually delivers a proliferative signal or whether, by promoting survival, proliferation results from signals other than the IL-7 receptor. We show that in an IL-7–dependent T cell line, cells protected from apoptosis nevertheless underwent cell cycle arrest after IL-7 withdrawal. This arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitor p27Kip1 through a posttranslational mechanism. Overexpression of p27Kip1 induced G1 arrest in the presence of IL-7, whereas knockdown of p27Kip1 by small interfering RNA promoted S phase entry after IL-7 withdrawal. CD4 or CD8 T cells transferred into IL-7–deficient hosts underwent G1 arrest, whereas 27Kip1-deficient T cells underwent proliferation. We observed that IL-7 withdrawal activated protein kinase C (PKC)θ and that inhibition of PKCθ with a pharmacological inhibitor completely blocked the rise of p27Kip1 and rescued cells from G1 arrest. The conventional pathway to breakdown of p27Kip1 is mediated by S phase kinase-associated protein 2; however, our evidence suggests that PKCθ acts via a distinct, unknown pathway inducing G1 arrest after IL-7 withdrawal from T cells. Hence, IL-7 maintains T cell proliferation through a novel pathway of p27Kip1 regulation.
Manual of Endocrine Surgery
Authors: R. Dale Liechty
Journal: JAMA (1976)

"We are particularly proud of the operative illustrations," the authors state in the introduction, and they have good right to be! With a color plate for almost every page, this manual pleasantly lives up to its intent: "... a comprehensive guide to the diagnosis and management of those endocrine diseases encountered by the general surgeon." Of course, a good surgical guide, like an authoritative travel guidebook, must include more than spectacular color pictures. It must point out the best and safest routes and warn us of dangers along the way. Again, this manual meets these objectives. To illustrate: the diagnosis of hyperparathyroidism depends on elevated serum calcium and parathormone levels in almost all patients. The authors highlight these two tests in large print and consign the others—determination of serum phosphorus level, tubular reabsorption of phosphate, the Dent test, and urinary excretion of calcium and cyclic adenosine monophosphate—to reduced type. Busy general
DNA microarray analysis of labial salivary glands of patients with Sjogren's syndrome
Authors: E. Wakamatsu, Y. Nakamura, I. Matsumoto, D. Goto, S. Ito, A. Tsutsumi, T. Sumida
Journal: Annals of the Rheumatic Diseases (2007)

Sjogren’s syndrome (SS) is a chronic autoimmune disease characterised by dry eyes, dry mouth and focal lymphocytic infiltration in lacrimal and salivary glands. The infiltrating lymphocytes are mainly CD4 α/β T cells,1 especially T helper 1 (Th1) type T cells, because they produce both interferon (IFN)γ and interleukin 2.2,3 To understand the pathogenesis of SS, several molecules in labial salivary glands (LSGs) have been screened by microarray analysis in human SS. Hjelmervik et al 4 and Gottenberg et al 5 reported that the upregulated genes in SS salivary glands were IFN-inducible genes, such as IFN-stimulated transcription factor 3, IFN-regulatory factor 1 and B cell-activation factor of the TNF family. …
Gilbert's syndrome
Authors: L. C. Claridge, M. J. Armstrong, C. Booth, P. S. Gill
Journal: BMJ (2011)

A 22 year old man presents with a resolving episode of mild jaundice after an influenza-like illness. He reports a previous episode after an appendicectomy, which also resolved spontaneously, but he is worried about the implications of this recurrence. Biochemical records from his surgical admission show a slightly raised bilirubin concentration of 48 µmol/l (normal < 22 µmol/l), but alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase and albumin were all within normal limits.

The history and biochemistry in this patient strongly suggest Gilbert’s syndrome, a hereditary (usually autosomal recessive) condition caused by impaired hepatic bilirubin clearance.1 Gilbert’s syndrome is present in 5-10% of Western European populations with 1 in 3 of those affected unaware that they have it.2 3 Diagnosis of the disorder is often made after an incidental finding of isolated hyperbilirubinaemia on routine liver biochemistry testing.

Bilirubin is the normal by-product of the breakdown of red blood cells (haemoglobin). Patients with Gilbert’s syndrome have a defect in the gene that encodes for glucuronyltransferase, which results in a 60-70% reduction in the liver’s ability to conjugate bilirubin. This subsequent increase …
A SPIRAL TROCAR AND ASPIRATING NEEDLE
Authors: Kelley Hale
Journal: JAMA (1927)

Several years ago I developed a small spiral trocar for introducing air into the abdominal cavity as a preliminary to celioscopy. I experimented on its introduction after making abdominal incisions. With the abdomen open, I found that, as the trocar was gently screwed through the abdominal wall, the point slowly and carefully passed through the peritoneum. In the closed abdomen, the moment of entrance of the point, air would rush in by aspiration through the hollow trocar. The danger of the patient jerking away from the instrument was eliminated, and it could be removed only by unscrewing in the opposite direction. The fear of having a hole punched into a bowel or lung by the use of the ordinary needle or trocar is greatly lessened by this spiral instrument. The sudden stab or punch by the present method is a thing of great dread to patients. Furthermore, the physician