tbuckley/cabot-search huggingface dataset:
Abstract A12: Regulation of ovarian cancer OVCAR-3 cell proliferation and viability by calcium/calmodulin-dependent protein kinase kinase 2
Authors: Angela M. Gocher, Gissou Azabdaftari, Arthur M. Edelman
Journal: Clinical Cancer Research (2013)

Abstract Protein kinases play crucial roles in cancer progression and are considered potential targets for novel anti-cancer therapeutics. Oncogenic kinases mediate a variety of events characteristic of the malignant phenotype including transcriptional activation, accelerated cell proliferation and enhanced cellular survival. Ca2+/Calmodulin-dependent Protein Kinase Kinase 2 (CaMKK2) has been implicated as a signaling mechanism in prostate and breast cancers, but has not been studied in ovarian cancer (OvCa). We report here the following. CaMKK2 expression is greatly increased in high grade serous papillary cystadenocarcinoma compared to benign tissue. Knockdown of CaMKK2 expression by RNA interference in OvCa OVCAR-3 cells resulted in slowing of cell growth and decreased number of cells entering S phase. At the molecular level, CaMKK2 knockdown led to significant decreases in cyclin D1 expression at both mRNA and protein levels and to a drop in phosphorylation of the retinoblastoma tumor suppressor (Rb) at Ser 807/811. These results indicate that CaMKK2 expression in OVCAR-3 OvCa cells is required for optimal G1/S phase cell cycle progression and proliferation. CaMKK2 knockdown also resulted in a significant decrease in OVCAR-3 cell survival and an increase in both Poly ADP Ribose Polymerase (PARP) cleavage (inactivation) and in the activity of executioner Caspases-3/7 indicating that CaMKK2 knockdown in OVCAR-3 cells results in apoptosis. Preliminary data showed a decrease in phosphorylation of the activation site of Akt (Thr 308) in CaMKK2 depleted cells suggesting that the G1/S phase cell cycle arrest and apoptosis in CaMKK2 silenced cells may occur either directly or indirectly through an Akt-dependent pathway. Altogether these data show that CaMKK2 is required for optimal growth and viability of OVCAR-3 cells and furthermore imply that CaMKK2 may be a promising and novel therapeutic target for OvCa. Citation Format: Angela M. Gocher, Gissou Azabdaftari, Arthur M. Edelman. Regulation of ovarian cancer OVCAR-3 cell proliferation and viability by calcium/calmodulin-dependent protein kinase kinase 2. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A12.
The Harvard Way
Authors: Raymond L. Singer
Journal: JAMA (1985)

<h3>To the Editor.—</h3> "The Harvard Way" is a telling description of how surgical residency programs are conducted at some "big-name" institutions. There are probably many other bright young men and women who bitterly drop out of surgical residencies because of the sort of inexcusable treatment Dr Walker experienced. One year ago, I was a medical student traveling around the country in search of a surgical residency. It appeared that the more prestigious the program, the more dissatisfied were the residents. The high-powered programs characteristically have steep pyramids, every-other-night on-call schedules, and top-heavy hands-on experience such that only the more senior residents are allowed to operate. After reading Dr Walker's essay, I became even more confident that I had made the right choice in selecting my surgical residency program. Thomas Jefferson University's program is well respected; at the same time, it is strictly nonpyramidal, the on-call schedule is, at most, every
Adverse effects of chronic cardiac denervation in conscious dogs with myocardial ischemia.
Authors: M Lavallee, J Amano, S F Vatner, W T Manders, W C Randall, J X Thomas
Journal: Circulation Research (1985)

The extent to which total chronic cardiac denervation protects the ischemic myocardium was investigated in conscious dogs. The major hemodynamic difference after coronary artery occlusion was that left ventricular end-diastolic pressure rose significantly more, P less than 0.01, in the denervated group (12 +/- 1.5 mm Hg) than in the normal group (4.4 +/- 1.4 mm Hg). Blood flow (radioactive microspheres) in the ischemic endo- and epicardium fell to similar levels at 3-5 minutes after coronary occlusion, but was significantly less (P less than 0.01) in denervated dogs at 3 hours after occlusion in the endo- (0.05 +/- 0.01) and epicardium (0.30 +/- 0.02 ml/min per g), than in the endo- (0.13 +/- 0.03) and epicardium (0.42 +/- 0.05 ml/min per g) in the normal group. A subgroup of normal dogs was also studied, with left ventricular end-diastolic pressure increased by volume loading to levels similar to those observed in the denervated group after coronary occlusion; in these dogs, blood flow was similar to that in the other two groups 3-5 minutes after coronary artery occlusion, but, at 3 hours, was significantly more depressed (P less than 0.01) than that observed in normal dogs without volume loading in both endo- (0.03 +/- 0.01) and epicardial (0.25 +/- 0.03 ml/min per g) layers. Infarct size, as a fraction of the area at risk, was significantly greater (P less than 0.05) in the denervated group (60 +/- 4.3%) and in the subgroup of normal dogs with elevated left ventricular end-diastolic pressure (73 +/- 5.8%), compared with the normal group without volume loading (37 +/- 8.1%). Thus, in conscious dogs, total chronic cardiac denervation exerts an adverse effect on infarct size which may be related to the sustained elevation in left ventricular end-diastolic pressure and consequent impairment of collateral perfusion.
In Vivo Gram Staining of Tinea Versicolor
Authors: Allyson Spence-Shishido, Christopher Carr, Michael Y. Bonner, Jack L. Arbiser
Journal: JAMA Dermatology (2013)

In this report, we demonstrate that tinea versicolor retains topical gentian violet. We did not observe this phenomenon in other hypopigmenting disorders, and thus this observation could be used as a simple bedside test. We call this phenomenon in vivo Gram staining.
Emergency Abdominal Surgery in Infancy, Childhood and Adult Life
Authors: Alvin M. Cotlar
Journal: JAMA (1974)

<i>Emergency Abdominal Surgery</i>extensively reviews the management of all types of abdominal catastrophes. The book, unfortunately sparsely illustrated, nevertheless is an invaluable handbook for the student and surgical house staff. The early chapters dealing with preoperative and postoperative care present practical recommendations. This early portion of the book also includes abdominal emergencies in the newborn, apparently a favorite subject of the author, a consultant in pediatric surgery at the University of Aberdeen. The text discusses the usual abdominal emergencies, such as appendicitis, intestinal obstruction, perforated ulcer, hematemesis, and melana, as well as unusual subjects of specialized interest (gynecologic, urologic, and others). The author approaches these conditions from the standpoint of etiology, incidence, diagnosis, and management. Numerous references from the world surgical bibliography are sometimes as recent as within one year of the book's publication. Dr. Jones, in presenting various techniques of management, offers his personal preference but at all times
The Contrasting Effects of Dopamine and Norepinephrine on Systemic and Splanchnic Oxygen Utilization in Hyperdynamic Sepsis
Authors: Paul E. Marik
Journal: JAMA (1994)

<h3>Objective.</h3> —To compare the effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in patients with hyperdynamic sepsis. <h3>Design.</h3> —A randomized short-term, interventional study. <h3>Setting.</h3> —An intensive care unit of a university hospital. <h3>Patients.</h3> —Twenty septic patients with a cardiac index greater than 3.2 L.min<sup>-1</sup>.m<sup>-2</sup>and either a mean arterial pressure (MAP) less than 60 mm Hg or a systemic vascular resistance index less than 1200 dyne.s.cm<sup>-5</sup>.m<sup>-2</sup>. <h3>Methods and Interventions.</h3> —Patients were randomized to receive an infusion of either dopamine or norepinephrine titrated to increase the MAP to greater than 75 mm Hg. The hemodynamic profile, oxygen delivery, oxygen consumption (determined by indirect calorimetry), and gastric intramucosal pH (pHi) (determined by gastric tonometry) were determined at baseline and after 3 hours of achieving the target MAP. <h3>Results.</h3> —Dopamine increased the MAP largely by increasing the cardiac index whereas norepinephrine increased the MAP by increasing the systemic vascular resistance index while maintaining the cardiac index. Although oxygen delivery and oxygen consumption increased in both groups of patients, the pHi increased significantly in those patients treated with norepinephrine whereas the pHi decreased significantly in those patients receiving dopamine (<i>P</i>&lt;.001, for corrected 3-hour value). <h3>Conclusions.</h3> —This study suggests that dopamine may cause an uncompensated increase in splanchnic oxygen requirements in septic patients. Norepinephrine, however, may have a more favorable hemodynamic profile and improve splanchnic tissue oxygen utilization in sepsis. (<i>JAMA</i>. 1994;272:1354-1357)
Progressive shortness of breath
Authors: K Guha, S Piper, P D Collins
Journal: BMJ (2009)

A 74 year old man reported increasing shortness of breath, which had progressed over the previous 18 months. He had three pillow orthopnoea and increasing peripheral oedema. The history indicated episodic minute haemoptysis. These symptoms were accompanied by intermittent fast palpitations. His medical history was unremarkable except for childhood rheumatic fever. He denied weight loss and smoking.

Examination showed NYHA II functional status. He was in a hypervolaemic state with a venous pressure at 4 cm, bibasal crackles, and pitting oedema bilaterally to mid-shin. On cardiovascular examination he had a pulse radially of 88 beats per minute irregularly irregular, and a pronounced mid-diastolic murmur associated with an opening snap heard loudest at the apex.⇓ 





### Short answers



Transthoracic echocardiogram, with colour Doppler (right). Ao=aorta, LA=left atrium, LV=left ventricle, MV=mitral valve, RA=right atrium, RV=right ventricle; arrow shows classic doming of mitral valve leaflet



### Discussion

Rheumatic fever, and subsequent rheumatic heart disease, was once the most common cause of mitral valve disease in both the West and worldwide. Due to the increasing availability and use of antibiotics, together with improved housing and social conditions, the incidence of rheumatic heart disease has steadily declined in Western populations, with an …
Mechanisms for Absence of Inverse Relationship Between Coupling Intervals of Premature Impulses Initiating Reentrant Ventricular Tachycardia and Intervals Between Premature and First Tachycardia Impulses
Authors: Candido Cabo, Bernard Deruyter, James Coromilas, Andrew L. Wit
Journal: Circulation (1997)

Background During initiation of tachycardias by programmed stimulation (PES), an inverse relationship between the coupling interval of the premature impulse (V 1 V 2 ) and the interval between the premature impulse and the first impulse of tachycardia (V 2 T 1 ) has been proposed to be a specific indicator of reentry. However, an inverse relationship has not always been observed during initiation of clinical reentrant ventricular tachycardias (VTs). Methods and Results Reentrant VT was initiated by PES in twelve 4-day-old infarcted dog hearts. The relationship between V 1 V 2 and V 2 T 1 was always direct. Mapping of the epicardial border zone (EBZ) indicated that initiation of VT was secondary to functional orthodromic block of V 2 , propagation of V 2 around the line of block, and antidromic propagation through the original location of the block. In 7 dogs, the line of orthodromic block and the pathway of orthodromic propagation were similar for different V 1 V 2 coupling intervals. Orthodromic conduction time around the line to its distal side was longer at shorter V 1 V 2 intervals, but a shorter antidromic delay in the area of unidirectional block for shorter V 1 V 2 intervals, possibly reflecting small changes in the conduction pathway involving deeper layers of the EBZ, resulted in shorter V 2 T 1 intervals. In the other 5 dogs, the orthodromic conduction pathway of V 2 around the line of block changed markedly, with a shorter pathway for shorter V 1 V 2 intervals resulting in shorter V 2 T 1 intervals. Conclusions An inverse relationship between V 1 V 2 and V 2 T 1 is not a specific indicator of functional reentry.
THE REMOVAL OF STAINS FROM THE TEETH CAUSED BY THE ADMINISTRATION OF MEDICINAL AGENTS AND THE BLEACHING OF PULPLESS TEETH.
Authors: A. W. HARLAN
Journal: JAMA (1885)

Read in the Section of Oral and Dental Surgery of the American Medical Association, May, 1884. Gentlemen:—A large number of remedial agents administered by physicians temporarily stain the teeth, but in looking over the list I find there are but few which may be said to permanently stain them. The mineral acids—nitric, sulphuric, hydrochloric, and other acids of this nature, if used for any length of time, may discolor the teeth and likewise have a deleterious effect on them; yet it cannot be said that such agents stain the teeth so that any particular method should be desired for restoring their natural appearance. The vegetable series may likewise be dismissed. The tannates and astringents generally do not permanently stain the teeth. The muriated tincture of iron, and in fact all of the ferrum preparations, with the single exception of ferrum dialystum, do stain the teeth; yet it is comparatively easy
Dr Alexis Carrel and Tissue Culture
Authors: J. A. Witkowski
Journal: JAMA (1984)

<h3>To the Editor.—</h3> The LANDMARK PERSPECTIVES that accompany the LANDMARK ARTICLES column in<i>JAMA</i>are presumably intended to give a historical perspective to the work reported in each LANDMARK ARTICLE. Such articles cannot be expected to be rigorous in their treatment of each topic, but this can be no excuse for the article by H. Najafi<sup>1</sup>commenting on the paper by Alexis Carrel. Najafi's article is an uncritical hagiography and perpetuates a view of Carrel's tissue culture studies that is not borne out by a close examination of Carrel's work. It is clear that while the work of Carrel's laboratory established tissue culture as a research technique of wide applicability, his writings on the difficulties of the method deterred others from following suit. A case can be argued that Carrel had an<i>adverse effect</i>on the development of tissue culture.<sup>2-4</sup> I have made a detailed study
Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes
Authors: Thati Madhusudhan, Hongjie Wang, Beate K. Straub, Elisabeth Gröne, Qianxing Zhou, Khurrum Shahzad, Sandra Müller-Krebs, Vedat Schwenger, Bruce Gerlitz, Brian W. Grinnell, John H. Griffin, Jochen Reiser, Hermann-Josef Gröne, Charles T. Esmon, Peter P. Nawroth, Berend Isermann
Journal: Blood (2011)
Infected appendiceal mucocele presenting as pyrexia of unknown origin
Authors: H. Udawat, A. Sharma, U. Dutta, T. Yadav, K. Vaiphei, S. Singh, R. Kochhar
Journal: Endoscopy (2008)

A mucocele of the appendix is defined as dilatation of the appendiceal lumen secondary to a variety of underlying pathological processes. Its presentation as pyrexia of unknown origin (PUO) has not been reported before. A 65-year-old man presented with a 3-month history of high-grade fever. Clinical examination and initial work-up for PUO was unremarkable. Contrast-enhanced abdominal computed tomography detected a well-defined, smooth, hypodense lesion at the base of the cecum ([Fig. 1]). A smooth filling defect, 1.5 cm × 1.5 cm in size, was seen on barium meal and follow through ([Fig. 2]). At colonoscopy, a smooth, indentable bulge (1.5 cm × 1.5 cm) was seen in the base of cecum with normal overlying mucosa ([Fig. 3]); the appendiceal opening was not visualized. When we took a biopsy from the lesion there was a gush of mucopurulent fluid. Culture of this fluid yielded growth of Gram-negative bacteria and anaerobes. The lesion collapsed and the appendiceal opening was then visible and found to be normal ([Fig. 4]). Biopsies of the lesion showed chronic inflammation. After drainage of the fluid and treatment with appropriate antibiotics the patient showed a dramatic reduction in his fever. Histopathological examination of tissue obtained from the appendectomy that was performed 2 weeks later was reported as suggestive of mucocele ([Fig. 5]).
Lymphocyte Stimulation in Malignant Melanoma
Authors: Herbert L. Cooper
Journal: New England Journal of Medicine (1970)

The notion that the body may attempt the immunologic rejection of neoplasms by reacting against antigens unique to the tumor has received increasing attention in recent years. It has been suggested that such activity occurs continuously, and that the growth of a tumor may signify a failure of this protective or "surveillance" mechanism.1 The nature of the immunologic response is thought to be the same as that responsible for the rejection of homografts. This involves a complex interaction among lymphocytes, macrophages and antigens, with the resultant infiltration of the offending tissue by activated lymphoid and phagocytic cells. These are thought . . .
Kidney donor is awarded 6.74m after "negligent and reckless" operation
Authors: C. Dyer
Journal: BMJ (2011)

<h3>Objective</h3> The aim of this study was to determine the effect of intra-muscular benztropine on pain and range of motion in patients presenting to the emergency department with acute, non-traumatic neck pain (wry neck). <h3>Methods</h3> In this two-centre randomised, double-blind, placebo-controlled, parallel-group superiority trial, participants were allocated to receive 2 mg intramuscular benztropine or normal saline. Participants were aged 16–65 years, no history of neck disorders and no use of medication that cause dystonia. Randomisation was computer generated, with allocation concealment by opaque sequentially numbered sealed envelopes. Pain scores and neck range of motion were measured immediately before drug administration, and 30 min after. Pain scores, range of motion and adverse effects were compared between the groups. No funding was received. The trial was registered. <h3>Results</h3> Thirty participants were enrolled, 15 randomised to placebo and 15 to benztropine. Pain scores at 30 min were lower in those allocated to benztropine, but the difference was neither statistically nor clinically significant (0.6 points, 95% CI −0.8 to 1.8, p=0.40). The range of motion of the cervical spine was greater in those receiving benztropine, but the differences were very small and not statistically significant. Adverse events were more common in those receiving benztropine. <h3>Conclusions</h3> Benztropine was ineffective for reducing pain or improving range of motion of the cervical spine in patients suffering from acute, non-traumatic neck pain, but frequently caused anticholinergic side effects. However, as the CI for the primary outcome included the minimum difference considered clinically significant, an important effect of benztropine cannot be ruled out. <h3>Trial registration number</h3> ANZCTR#12612000354886
A Single Nucleotide Polymorphism in <i>STK11</i> Influences Insulin Sensitivity and Metformin Efficacy in Hyperinsulinemic Girls With Androgen Excess
Authors: Abel López-Bermejo, Marta Díaz, Erica Morán, Francis de Zegher, Lourdes Ibáñez
Journal: Diabetes Care (2010)

Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry.Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P < 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P < 0.005).In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.
Health repercussions of the Harman case
Authors: J. Warden
Journal: BMJ (1996)

Harriet Harman, the shadow health secretary, was asked recently if Labour's future health policy would come in one big bang or in a series of little bangs. Neatly she replied that it would be a series of big bangs. But not even she was prepared for the big bang that exploded a week later.

The detonator was Ms Harman's decision to enrol her 11 year old son at a grammar school which, although in the state sector, operates selective entry. For parents caught in the educational rat race of south east England a grammar school place is the next best thing to winning the lottery. But for a Labour party member it is also heresy to defy the …
Clinical trials update from the American Heart Association meeting 2009: HEAAL, FAIR‐HF, J‐CHF, HeartMate II, PACE and a meta‐analysis of dose‐ranging studies of beta‐blockers in heart failure
Authors: John G.F. Cleland, Alison P. Coletta, Nick Freemantle, Daniyal Ahmed, Pawel Rubis, Andrew L. Clark
Journal: European Journal of Heart Failure (2010)
Expect the Unexpected in Hepatitis
Authors: Samuel Vaisrub
Journal: JAMA (1974)

Even though it is known that the virus of hepatitis A may be transmitted by the parenteral route,<sup>1</sup>we hardly ever think of this possibility when hepatitis follows transfusion of blood or blood products. Almost invariably, we assume that the disease is hepatitis B. Meyers et al<sup>2</sup>remind us that this assumption can be misleading. They have investigated an outbreak of hepatitis in a bone marrow transplant unit. Overt disease developed within a period of three months in nine patients with a marrow transplant and in six donor-members of their families. Subclinical hepatitis, evidenced by increased serum glutamic oxalacetic transaminase concentrations, was detected in 21 additional cases among family members, staff members, and other donors, and 69% of patients receiving platelet transfusion during the period of risk. Unexpectedly, the short incubation period as well as the clinical and serological features of the illness were compatible with<i>hepatitis A</i>