tbuckley/cabot-search huggingface dataset:
Characterization of a Novel PERK Kinase Inhibitor with Antitumor and Antiangiogenic Activity
Authors: Charity Atkins, Qi Liu, Elisabeth Minthorn, Shu-Yun Zhang, David J. Figueroa, Katherine Moss, Thomas B. Stanley, Brent Sanders, Aaron Goetz, Nathan Gaul, Anthony E. Choudhry, Hasan Alsaid, Beat M. Jucker, Jeffrey M. Axten, Rakesh Kumar
Journal: Cancer Research (2013)

The unfolded protein response (UPR) is a signal transduction pathway that coordinates cellular adaptation to microenvironmental stresses that include hypoxia, nutrient deprivation, and change in redox status. These stress stimuli are common in many tumors and thus targeting components of the UPR signaling is an attractive therapeutic approach. We have identified a first-in-class, small molecule inhibitor of the eukaryotic initiation factor 2-alpha kinase 3 (EIF2AK3) or PERK, one of the three mediators of UPR signaling. GSK2656157 is an ATP-competitive inhibitor of PERK enzyme activity with an IC(50) of 0.9 nmol/L. It is highly selective for PERK with IC(50) values >100 nmol/L against a panel of 300 kinases. GSK2656157 inhibits PERK activity in cells with an IC(50) in the range of 10-30 nmol/L as shown by inhibition of stress-induced PERK autophosphorylation, eIF2α substrate phosphorylation, together with corresponding decreases in ATF4 and CAAT/enhancer binding protein homologous protein (CHOP) in multiple cell lines. Oral administration of GSK2656157 to mice shows a dose- and time-dependent pharmacodynamic response in pancreas as measured by PERK autophosphorylation. Twice daily dosing of GSK2656157 results in dose-dependent inhibition of multiple human tumor xenografts growth in mice. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect. However, despite its antitumor activity, given the on-target pharmacologic effects of PERK inhibition on pancreatic function, development of any PERK inhibitor in human subjects would need to be cautiously pursued in cancer patients.
Prospective cohort study of factors influencing the relative weights of the placenta and the newborn infant
Authors: L. A Williams, S. F Evans, J. P Newnham
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To determine the demographic, environmental, and medical factors that influence the relative weights of the newborn infant and the placenta and compare this ratio with other factors known to predispose to adult ill health. <b>Design:</b> Prospective cohort study. <b>Setting:</b> The tertiary referral centre for perinatal care in Perth, Western Australia. <b>Subjects:</b> 2507 pregnant women who delivered a single live infant at term. <b>Main outcome measures:</b> Placental weight, birth weight, and the ratio of placental weight to birth weight. <b>Results:</b> By multiple regression analysis the placental weight to birthweight ratio was significantly and positively associated with gestational age, female sex, Asian parentage, increasing maternal body mass index, increased maternal weight at booking, lower socioeconomic status, maternal anaemia, and increasing number of cigarettes smoked daily. There were no consistent relations between the placental weight to birthweight ratio and measures of newborn size. <b>Conclusions:</b> The ratio of placental weight to birth weight is not an accurate marker of fetal growth. In its role as a predictor of adult disease the ratio may be acting as a surrogate for other factors which are already known to influence health and may act before or after birth. Determining the role that relative growth rates of the fetus and placenta have in predisposing to adult disease requires prospective study to account for the many confounding variables which complicate this hypothesis. <h3>Key messages</h3> Retrospective analyses have identified an association between a raised placental weight to birthweight ratio and hypertension in adulthood Accurate estimation of gestational age is crucial when interpreting the placental weight to birthweight ratio Environmental factors associated with alterations in the placental weight to birthweight ratio may not exert their effects exclusively in the antenatal period As a marker of fetal growth the potential usefulness of the placental weight to birthweight ratio is diminished because the ratio is influenced by a multiplicity of factors Prospective study is required to clarify the role of intrauterine programming in the genesis of adult disease
Longitudinal Assessment of Glycosylated Blood Protein Concentrations in Normal Pregnancy and Gestational Diabetes
Authors: Mary Ann Morris, Arnold S Grandis, Jean C Litton
Journal: Diabetes Care (1986)

Longitudinal changes in glycosylated hemoglobin concentration (GlyHb) and glycosylated serum protein concentration (GSP) in both normal pregnancy and pregnancy complicated by gestational diabetes were determined using affinity chromatography, a method in which nonenzymatically glycosylated proteins are specifically measured. At 7–10 wk gestation, GlyHb in women who developed diabetes (N = 21) was higher than GlyHb in normal women (N = 49) (6.7 ± 0.2% versus 5.7 ± 0.2%, respectively, P &amp;lt; 0.001) and remained elevated throughout gestation. In normal pregnancy, GlyHb decreased to a nadir at 23–26 wk and returned to baseline concentration by 31–34 wk. In gestational diabetes, there was an initial increase in GlyHb to 7.1 ± 0.5% at 11–14 wk followed by a steady decrease. At 7–10 wk, GSP in women who developed diabetes was not elevated compared with normal concentration, although at 11–14 wk there was significant difference between the two groups (P &amp;lt; 0.02). In normal women, GSP remained constant throughout gestation. In gestational diabetes, GSP decreased to early pregnancy values (P &amp;lt; 0.02). Glycosylated blood proteins were elevated in early gestation in women who developed gestational diabetes and may have predictive value in identifying women who will develop diabetes in pregnancy.
The Disinfection of Phthisical Sputum
Authors: H. Handford
Journal: BMJ (1886)

descending from his warehouse, fell off the ladder astride the iron handle of a truck standing vertically.Shortly after the accident, in trying to relieve the desire for micturition, he noticed a stream of blood coming from his meatus, followed with difficulty in the passage of urine.He lost about two ounces of blood.October 5th, 1885.He at once sent for me, and on examination the perinnum was found to be slightly swollen, excessively tender, with a small skin-abrasion in the centre.He was ordered a hip-bath, and sent to bed.A few hours later, with the assistance of my father, all our attempts to pass a catheter failed, a quantity of blood followed these attempts.Warm fomentations were applied to the perinaum, which somewhat relieved the pain.October 6th.Micturition was difficult and painful; the urine was pre- cededby afew drops of blood, and followed by a "peculiar creeping, smart- ing sensation," referred by the patient to the perinneum.The swelling in the perinseum had increased, and become harder.There was no oozing from the skin-abrasion.Temperature 1000 Fahr.For the next three days, his temperature ranged between 100°Fahr.and 1010 Fahr.
Hypertriglyceridemic Waist
Authors: Isabelle Lemieux, Agnès Pascot, Charles Couillard, Benoı̂t Lamarche, André Tchernof, Natalie Alméras, Jean Bergeron, Daniel Gaudet, Gérald Tremblay, Denis Prud’homme, André Nadeau, Jean-Pierre Després
Journal: Circulation (2000)

Background —The present study tested the hypothesis that simple variables, such as waist circumference and fasting plasma triglyceride (TG) concentrations, could be used as screening tools for the identification of men characterized by a metabolic triad of nontraditional risk factors (elevated insulin and apolipoprotein [apo] B and small, dense LDL particles). Methods and Results —Results of the metabolic study (study 1) conducted on 185 healthy men indicate that a large proportion (&gt;80%) of men with waist circumference values ≥90 cm and with elevated TG levels (≥2.0 mmol/L) were characterized by the atherogenic metabolic triad. Validation of the model in an angiographic study (study 2) on a sample of 287 men with and without coronary artery disease (CAD) revealed that only men with both elevated waist and TG levels were at increased risk of CAD (odds ratio of 3.6, P &lt;0.03) compared with men with low waist and TG levels. Conclusions —It is suggested that the simultaneous measurement and interpretation of waist circumference and fasting TG could be used as inexpensive screening tools to identify men characterized by the atherogenic metabolic triad (hyperinsulinemia, elevated apo B, small, dense LDL) and at high risk for CAD.
Determinants of Compliance With a National Smoke-Free Hospital Standard
Authors: Anne M. Joseph
Journal: JAMA (1995)

To determine the extent of compliance with the new Joint Commission on Accreditation of Healthcare Organizations (JCAHO) standard requiring acute care hospitals to be smoke-free, and to identify predictors of adoption of smoke-free hospital policies.We conducted a survey of a national sample of acute care hospitals and developed a predictive model for implementation of smoke-free policies during multiple logistic regression. We examined numerous factors that might predict adoption of smoke-free policies, such as hospital characteristics, patient care services, and experience with smoke-free initiatives.A systematic 20% sample of JCAHO-accredited hospitals in the United States (n = 1278). Military, Department of Veterans Affairs, Indian Health Service, psychiatric, substance abuse treatment, and children's hospitals were excluded.Compliance with the JCAHO standard.The response rate was 85%. Six-five percent of hospitals were in compliance with the standard 16 months after it was introduced. Factors that were independently and positively associated with implementation of smoke-free policies were administrative support (odds ratio [OR], 7.82; 95% confidence interval [Cl], 2.05 to 29.65) and inpatient smoking cessation services (OR, 1.24; 95% Cl, 1.02 to 1.52). Factors negatively associated with implementation of smoke-free policy were the number of psychiatric treatment beds (OR, 0.57; 95% Cl, 0.14 to 0.81), number of substance abuse treatment beds (OR, 0.17; 95% Cl, 0.11 to 0.26), and presence of an active task force to address smoking policy (OR, 0.56; 95% Cl, 0.40 to 0.77).The majority of acute care hospitals are in compliance with the JCAHO national smoke-free policy initiative. The standard is well accepted by most patients and employees. It is critical to address the challenges presented by special populations, such as psychiatry patients, to accomplish the goal of completely smoke-free hospitals.
Determination of the Percentage of Free Prostate&amp;ndash;Specific Antigen Helps to Avoid Unnecessary Biopsies in Men with Normal Rectal Examinations and Total Prostate&amp;ndash;Specific Antigen of 4&amp;ndash;10 ng&amp;sol;ml
Authors: L. Mart&iacute;nez-Pi&ntilde;eiro, A. Tabernero, T. Contreras, R. Madero, D. Lozano, J. L&oacute;pez-Tello, J.M. Alonso-Dorrego, M.L. Picazo, P. Gonz&aacute;lez Gancedo, J.A. Mart&iacute;nez-Pi&ntilde;eiro, J.J. de la Pe&ntilde;a
Journal: European Urology (2000)
Vitamin D deficiency and deafness.
Authors: E B Brookes, A W Morrison
Journal: BMJ (1981)

Chloramphenicol -resistant Salmonella typhimurium meningitis in an adultSalm?onella tvphimuiruoiz meningitis is virtually unknown in adults.'We report such a case, complicated by chloramphenicol resistance of the organism and a preterminal cerebellar abscess. Case reportA 65-yvear-old wonman with maturity-onset diabetes and a history of cholecystectomlly was admittcd to the infection unit with a three-day history of diarrhoea and vomiting.She was feverish (39 C), had a headache, and was confused, dehydrated, and semiconscious Xwith pronounccd ncekstiffncss.Tlhcre was nystagmus oII horizontal and vertical gaze and mild left Horner's syndrome.Lumbar puncture produced turbid cerebrospinal fluid with distinct polymorph pleocytosis (4-6 10'/1and a protcin concentration of over 10 gIl.Ccrcbrospinal fluid glucose concentration was 18-8 mmol/l (339 mg, 100 ml) and plasma glucosc 33-8 mmol/l (609 mg/100 ml).No organisms were seen on microscopy, but bacterial meningitis was diagnosed clinically and anti- microbial treatment started 'with high-dosage intravenous bolus benzylpcnicillin, gcntamicin, and metronidazole to cover a range of possibilitics.Peripheral wlhite cell count was 12-3 109/1 with 800,, neutrophils.Radio-
Consent for Analgesia
Authors: H. Close Hesseltine
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In your Questions and Answers section (<i>JAMA</i><b>180</b>:181 [April 14] 1962), under the question about consent for analgesia, Dr. Richard P. Bergen offers this one-sentence statement: "The patient is legally entitled to decide whether or not to receive anesthetics and to specify the type of anesthetic, if he chooses." The first part of this sentence is correct. The patient has the legal right to decide whether he or she will submit to operations and will submit to a type of anesthesia. The patient may have a preference, but the doctor must make the medical decision and so recommend. The physician, either the anesthetist or the surgeon or both, must make the medical recommendation. The patient is not qualified medically to decide. The patient is entitled to express a preference. If those responsible cannot convince the patient of the proper course, they must not let the patient
Swine flu website inundated as cases in England double in a week
Authors: N. Siva
Journal: BMJ (2009)

The Department of Health for England said that the number of cases of influenza A/H1N1 has almost doubled, increasing to 100 000, from about 55 000 a week ago.

The rise in cases led to an unprecedented number of people trying to access the government’s new online diagnosis service when it was launched at 3 pm on 23 July. 

The site was designed to handle 1200 hits a second but had to be suspended within four minutes of launching when 2600 people tried to access it every second, equivalent to 9.3 million hits per hour. The department denied that the site had crashed and …
Extraosseous Skin and Subcutaneous Tissue Uptake of Tc-99m HMDP in a Surgical Scar After Laparotomy
Authors: Tsuyoshi Hashimoto, Kiyoshi Koizumi, Noboru Hanawa, Kimihiko Abe
Journal: Clinical Nuclear Medicine (2003)

A 76-year-old man showed extraosseous accumulation of Tc-99m HMDP in a surgical scar after laparotomy. A surgical scar is one of the major causes of extraosseous skin and subcutaneous uptake of bone-imaging agents. However, it might be difficult to diagnose if this fact is not known. If such an accumulation is suspected during the study, additional appropriate views (such as oblique or lateral views) are required in addition to routine anterior and posterior views to prove that this accumulation really exists on the body surface.
Preventing Bone Loss During Androgen Deprivation Therapy for Prostate Cancer: Early Experience with Neridronate
Authors: Carlo Magno, Giuseppina Anastasi, Nunziata Morabito, Agostino Gaudio, Domenica Maisano, Fabio Franchina, Alessandro Galì, Nicola Frisina, Darwin Melloni
Journal: European Urology (2005)
The 2013 American Association of Clinical Endocrinologists’ Diabetes Mellitus Management Recommendations
Authors: Michael R. Gionfriddo, Rozalina G. McCoy, Kasia J. Lipska
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Alpha beta but not gamma delta T cell clones in synovial fluids of patients with reactive arthritis show active transcription of tumour necrosis factor and interferon 
Authors: M Rihl
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To compare the cytokine expression profile of three CD8+, three CD4+, and three γδ+ T cell clones all derived from the synovial fluids of three patients with reactive arthritis (ReA). <b>Methods:</b> Complementary DNA based microarrays containing the specific sequence of 56 cytokine transcripts were used for screening. Selected genes were confirmed by reverse transcriptase-polymerase chain reaction assay. <b>Results:</b> Microarray showed that transcripts encoding for interferon γ and tumour necrosis factor α were expressed by all CD8+ and CD4+ T cell clones. However, γδ+ T cells predominantly expressed transforming growth factor β2 and granulocyte monocyte-colony stimulating factor. <b>Conclusion:</b> T lymphocyte clones from the joint of patients with ReA exhibit differential cytokine expression profiles. CD8+ and CD4+ T cells demonstrate a Th1 mediated profile, whereas γδ+ T cells show a more heterogeneous and less proinflammatory Th3 driven pattern.
Acupuncture and possible hepatitis B infection
Authors: F. P. Li
Journal: JAMA (1980)

To the Editor.—  During a recent three-month stay in China under a research program sponsored by the US National Academy of Sciences, we noted considerable diversity in methods of disinfection of soiled acupuncture needles. Despite increased popularity of the treatment in the United States, little attention has been given to the adequacy of disinfection of acupuncture needles by physicians and other practitioners.  In hospitals and urban clinics in China, contaminated acupuncture needles are usually disinfected in the same manner as other needles and surgical instruments. However, barefoot doctors in several rural areas reported that they cleanse acupuncture needles solely by soaking or wiping with alcohol. The procedure does not meet generally recommended standards for protection against transmission of hepatitis B infection. 1 Chinese scientists are aware of the problem and recognize that hepatitis is prevalent in China. Transmission of the disease via acupuncture needles can be studied through assays for
Effective Tobacco Dependence Treatment
Authors: Michael C. Fiore
Journal: JAMA (2002)

MORE THAN AT ANY TIME IN the past, clinicians, public health professionals, and policy makers now possess sufficient evidence to implement effective tobacco dependence treatment programs and policies. We review key findings of great relevance to treating tobacco dependence: clinical, health system, and community interventions can each independently foster tobacco cessation. A transdisciplinary approach that incorporates all of these components holds the greatest promise for reducing population-based rates of tobacco use. If these interventions are implemented broadly, a larger proportion of the 46 million US adult smokers will try to quit. Among those who do try, the likelihood of successful cessation will increase substantially.
Genome-Wide Analysis of Survival in Early-Stage Non–Small-Cell Lung Cancer
Authors: Yen-Tsung Huang, Rebecca S. Heist, Lucian R. Chirieac, Xihong Lin, Vidar Skaug, Shanbeh Zienolddiny, Aage Haugen, Michael C. Wu, Zhaoxi Wang, Li Su, Kofi Asomaning, David C. Christiani
Journal: Journal of Clinical Oncology (2009)

Lung cancer, of which 85% is non-small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC.
Is it time for medicine to update its Facebook status?
Authors: A. Osman, A. Wardle
Journal: BMJ (2011)

Facebook focuses on, “Giving people control over their experience so they can express themselves freely while knowing that their information is being shared in the way they intend.”1 This ethos relies on members having the correct perception of how their information is shared, as is shown by the privacy problems experienced by practising doctors.2 …
Striving to recruit: the difficulties of conducting clinical research on elderly care home residents
Authors: A. G Zermansky, D. P Alldred, D. R Petty, D. K Raynor
Journal: Journal of the Royal Society of Medicine (2007)

Elderly care home residents are a distinct group of over 440 000 people in over 18 000 homes in England.1 Their mortality,2 health status and needs3,4 are different from those of people of the same age living in their own homes. Indeed, their physical and/or mental frailty and multiple pathology is usually the reason why they live in a residential setting. They are so different in almost every way from people of the same age in their own homes that research outcomes on the latter are simply not valid for them and it is important to conduct research specifically on care home residents.

Conducting research on care home residents is beset with constraints and complexities that can impair progress. Careful planning and an extraordinary amount of time and resources are needed to overcome them. We recently completed a large randomized controlled trial of clinical medication review by a pharmacist of elderly residents of care homes.5 In the process we encountered and struggled with many these problems. We hope that, by highlighting the issues and pitfalls, we can help future researchers plan projects involving care home residents.
Scalene-Lymph-Node Biopsy
Authors: David B. Skinner
Journal: New England Journal of Medicine (1963)

SHOULD scalene-lymph-node biopsy be performed routinely in patients suspected of having lung cancer? What are the risks of the operation and the expected yield of positive results in various clinical syndromes? Reports of series of biopsies provide little information to assist the physician in deciding when a biopsy is indicated. This is a report of five years' experience with scalene-lymph-node biopsy at the Massachusetts General Hospital undertaken to assess the clinical value and risk, and to determine specific indications for this procedure.Materials and MethodsIn this hospital, from 1957 through 1961, 260 biopsies were performed through supraclavicular incisions. The . . .
IDENTIFICATION OF SALIVARY BIOMARKERS OF ACUTE MYOCARDIAL INFARCTION USING CLASSIFICATION AND REGRESSION TREE ANALYSIS
Authors: Joseph D. Foley, Charles L. Campbell, Craig S. Miller, J. Darrell Sneed, Alison L. Bailey, Dawn G. Dawson, Pierre N. Floriano, Nicolaos Christodoulides, Beate G. Rose, Jackie Singleton, Jeffrey L. Ebersole, Steven Steinhubl, Denis F. Kinane, Richard J. Kryscio, M. John Novak, John T. McDevitt
Journal: Journal of the American College of Cardiology (2010)