tbuckley/cabot-search huggingface dataset:
Synthetic Lethality — A New Direction in Cancer-Drug Development
Authors: J. Dirk Iglehart, Daniel P. Silver
Journal: New England Journal of Medicine (2009)

In this issue of the Journal, Fong et al. report the results of a phase 1 trial of a new cancer therapy involving 60 patients (ClinicalTrials.gov number, NCT00516373).1 Readers may be surprised by the editors' decision to publish a small early-stage trial, but this trial not only reports important results — it also points to a new direction in the development of anticancer drugs. Modern cancer-drug discovery focuses on finding new therapies with few side effects by leveraging advances in the understanding of cancer biology, but barriers to success are substantial. The story behind the report by Fong et al. . . .
Safety and activity of trastuzumab-containing therapies for the treatment of metastatic breast cancer: our long-term clinical experience (GOIM study)
Authors: V. Adamo, T. Franchina, B. Adamo, G. Ferraro, R. Rossello, M. Maugeri Saccà, C. Scibilia, M.R. Valerio, A. Russo
Journal: Annals of Oncology (2007)
Opportunities for Providing Web-Based Interventions to Prevent Sexually Transmitted Infections in Peru
Authors: Walter H Curioso, Magaly M Blas, Bobbi Nodell, Isaac E Alva, Ann E Kurth
Journal: PLoS Medicine (2007)

HIV is one of the biggest infectious killers worldwide, causing 8,000 deaths a day in 2005 [1]. In Latin America, an estimated 1.8 million people are living with HIV [1], and in 2005, about 66,000 people died of AIDS and 200,000 were newly infected with HIV [1].

In Peru, the HIV/AIDS epidemic has largely been concentrated among men who have sex with men (MSM) and female sex workers [2,3]. The seroprevalence rate for MSM is 10%–22% [3–5], compared to 0.1%–0.4% for the general population [6]. The prevalence of other sexually transmitted infections (STIs) among the MSM population is also high: 13.4% for syphilis and 46.3% for herpes simplex virus type 2 [3].

Even though the HIV/AIDS epidemic is confined to high-risk groups, there is significant risk for a wider HIV spread. A 2005 study in young males from socioeconomically disadvantaged populations showed that at least 14.2% of them had a male sexual partner in the last six months, and 86.3% of those who had a male sexual partner also had female partners in the same period [7]. Most of these young men's sexual encounters with male partners (56.9%) and female partners (84.2%) were unprotected [7].
Myocardin Functions as an Effective Inducer of Growth Arrest and Differentiation in Human Uterine Leiomyosarcoma Cells
Authors: Yasunori Kimura, Tsuyoshi Morita, Ken'ichiro Hayashi, Tsuneharu Miki, Kenji Sobue
Journal: Cancer Research (2010)

Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. We noticed that the expression of myocardin was markedly downregulated in human uterine leiomyosarcoma cells. Restoration of myocardin expression induced the reexpression of smooth muscle marker proteins and the formation of well-developed actin fibers. A concomitant increase in the expression of a cyclin-dependent kinase inhibitor, p21, led to significantly reduced cell proliferation, via p21's inhibition of the G(1)-S transition. A p21 promoter-reporter assay showed that myocardin markedly increased p21's promoter activity. Furthermore, a serum response factor (SRF)-binding cis-element CArG box in the p21 promoter region was required for this myocardin effect. Chromatin immunoprecipitation and DNA-protein binding assays showed that myocardin indirectly bound to the CArG box in the p21 promoter through the interaction with SRF. Furthermore, immunohistochemistry revealed that the levels of myocardin and p21 were both lower in leiomyosarcoma samples than in normal smooth muscle tissue. Taken together, our results indicate that the downregulation of myocardin expression facilitates cell cycle progression via the reduction of p21 expression in human leimyosarcomas and suggest that myocardin could be a useful therapeutic target for this disease.
Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003
Authors: Pardeep S. Jhund, Kate MacIntyre, Colin R. Simpson, James D. Lewsey, Simon Stewart, Adam Redpath, James W.T. Chalmers, Simon Capewell, John J.V. McMurray
Journal: Circulation (2009)

We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF.All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, beta-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend).After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.
Small-Molecule RA-9 Inhibits Proteasome-Associated DUBs and Ovarian Cancer <i>In Vitro</i> and <i>In Vivo</i> via Exacerbating Unfolded Protein Responses
Authors: Kathleen Coughlin, Ravi Anchoori, Yoshie Iizuka, Joyce Meints, Lauren MacNeill, Rachel Isaksson Vogel, Robert Z. Orlowski, Michael K. Lee, Richard B.S. Roden, Martina Bazzaro
Journal: Clinical Cancer Research (2014)

Ovarian cancer is the deadliest of the gynecologic malignancies. Carcinogenic progression is accompanied by upregulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUB) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer.The potency and selectivity of RA-9 inhibitor for proteasome-associated DUBs was determined in ovarian cancer cell lines and primary cells. The anticancer activity of RA-9 and its mechanism of action were evaluated in multiple cancer cell lines in vitro and in vivo in immunodeficient mice bearing an intraperitoneal ES-2 xenograft model of human ovarian cancer.Here, we report the characterization of RA-9 as a small-molecule inhibitor of proteasome-associated DUBs. Treatment with RA-9 selectively induces onset of apoptosis in ovarian cancer cell lines and primary cultures derived from donors. Loss of cell viability following RA-9 exposure is associated with an unfolded protein response as mechanism to compensate for unsustainable levels of proteotoxic stress. In vivo treatment with RA-9 retards tumor growth, increases overall survival, and was well tolerated by the host.Our preclinical studies support further evaluation of RA-9 as an ovarian cancer therapeutic.
Mutational and Radiographic Analysis of Pulmonary Disease Consistent with Lymphangioleiomyomatosis and Micronodular Pneumocyte Hyperplasia in Women with Tuberous Sclerosis
Authors: DAVID NEAL FRANZ, ALAN BRODY, CRISTOPHER MEYER, JENNIFER LEONARD, GAIL CHUCK, SANDRA DABORA, GOPALAN SETHURAMAN, THOMAS V. COLBY, DAVID J. KWIATKOWSKI, FRANCIS X. Mc CORMACK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH) produce cystic and nodular disease, respectively, in the lungs of patients with tuberous sclerosis. The objective of this study was to prospectively characterize the prevalence, clinical presentation, and genetic basis of lung disease in TSC. We performed genotyping and computerized tomographic (CT) scanning of the chest on 23 asymptomatic women with tuberous sclerosis complex (TSC). Cystic pulmonary parenchymal changes consistent with LAM were found in nine patients (39%). These patients tended to be older than cyst-negative patients (31.9 +/- 7.6 yr versus 24.8 +/- 11.6 yr, p = 0.09). There was no correlation between presence of cysts and tobacco use, age at menarche, history of pregnancy, or estrogen-containing medications. Three of the cyst-positive patients had a prior history of pneumothorax. Pulmonary function studies revealed evidence of gas trapping but normal spirometric indices in the cyst-positive group. All nine cyst-positive patients had angiomyolipomas (AML), which were larger (p < 0.05) and more frequently required intervention (p = 0.08) than cyst-negative patients (8 of 14 with AMLs, p < 0.05). Ten patients (43%) had pulmonary parenchymal nodules. Pulmonary nodules were more common in women with cysts (78% versus 21%, p < 0.05), and 52% of all patients had either cystic or nodular changes. TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease. Correlation of the mutational and radiographic data revealed one pair of sisters who were discordant for cystic disease, two mother- daughter pairs who were discordant for nodular disease, and no clear association between cyst development and a specific mutational type. This prospective analysis demonstrates that cystic and nodular pulmonary changes consistent with LAM and MMPH are common in women with TSC.
COMPARISON OF TRANSRADIAL CORONARY INTERVENTION BETWEEN RIGHT AND LEFT RADIAL APPROACH
Authors: Young Jin Youn, Junghan Yoon, Sang Woo Han, Jun-Won Lee, Joong Kyung Sung, Nam Seok Lee, Jang-Young Kim, Seung Hwan Lee, Kyung-Hoon Choe
Journal: Journal of the American College of Cardiology (2010)
ARTERIOLES OF THE RETINA IN TOXEMIA OF PREGNANCY
Authors: HENRY P. WAGENER
Journal: JAMA (1933)

That retinitis occurs with some forms of toxemia of pregnancy is recognized. However, the clinical significance of such retinitis is not well understood. There have been two main sources of difficulty in the interpretation of its relation to the underlying disease: (1) the varying terminology used by ophthalmologists to describe and designate the retinitis, and (2) the varying classifications of toxemia by obstetricians and clinicians. Although greater uniformity is being gradually attained in both of these phases, it is still hard to avoid the rather meaningless term albuminuric retinitis, and it is still difficult immediately to classify individual cases of toxemia with absolute accuracy. It does not seem feasible at the present time to attempt to prove that retinal lesions occur exclusively in any one type of toxemia of pregnancy. It does seem, however, that the changes seen in the retinas of patients with toxemia are sufficiently constant to furnish,
Survey of treatment of primary breast cancer in Great Britain.
Authors: J C Gazet, R M Rainsbury, H T Ford, T J Powles, R C Coombes
Journal: BMJ (1985)

A postal survey of current management of breast cancer among surgeons in Great Britain was carried out. The results showed that there is no consensus among surgeons about the treatment of primary breast cancer. Many different types of primary surgery are practised, and patterns of referral for postoperative radiotherapy vary widely. Adjuvant systemic treatment is given often by some surgeons and not at all by others. Few patients are entered into controlled randomised trials.
Approval Expected for `Prelude' to Gene Therapy
Authors: Charles Marwick
Journal: JAMA (1989)

AUTHORIZATION TO INSERT a gene into humans is imminent. It only remains for James B. Wyngaarden, MD, National Institutes of Health (NIH) director, and Frank E. Young, MD, Food and Drug Administration (FDA) commissioner, to give approval, which they are expected to do this month. The numerous reviews are an indication of the care with which this proposal was considered (<i>JAMA</i>1988;260:2783). Even though "it does not constitute gene therapy<i>per se</i>, it must be regarded as a prelude to such experiments," Wyngaarden has noted. The work involves placing the gene for neomycin resistance into tumorinfiltrating lymphocytes as a marker for following the fate of these cells when they are injected into cancer patients. The use of the gene is not directly therapeutic, although the goal is an improved antitumor regimen. The tumor-infiltrating lymphocytes are cultures of cells obtained from the patient's tumor and subsequently injected back into the patient.
HELLP Syndrome: Hemolysis, Elevated Liver Enzymes, and Low Platelets
Authors: John H. Stone
Journal: JAMA (1998)

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
European Union leads way on e-health, but obstacles remain
Authors: R. Watson
Journal: BMJ (2010)

The European Union is leading the world in the development of new technology in health care, such as electronic patient records and telemedicine, but serious political, legal, and practical obstacles to its wider use remain. This is among the preliminary findings of a study conducted for the European Commission.

The study, which is due to be formally launched next month, notes that overall there is strong momentum behind the planning and implementation of national and regional e-health infrastructure. But responsibility for e-health strategies in EU member states is not uniform. In most countries this responsibility lies largely …
Herpes Simplex Virus Type 1 DNA in Cerebrospinal Fluid of a Patient with Mollaret's Meningitis
Authors: Linda J. Yamamoto, Davol G. Tedder, Rhoda Ashley, Myron J. Levin
Journal: New England Journal of Medicine (1991)

MOLLARET'S meningitis is a rare disease characterized by recurrent, self-limited episodes of aseptic meningitis.1 Signs and symptoms of meningeal irritation appear acutely, in association with fever and pleocytosis of mononuclear cells. These episodes last two to five days or occasionally longer and remit spontaneously.2–6 Five to 15 attacks may occur, separated by symptom-free intervals of weeks to months. Transient neurologic abnormalities may be present during the attacks, but they disappear after the acute illness. The diagnosis of Mollaret's meningitis is made only after other recognized causes of recurrent lymphocytic meningitis have been excluded.2 Numerous attempts to establish a microbiologic cause . . .
Occupational hazard of infection in the operating theatre
Authors: J McKie, A Shaw
Journal: BMJ (1981)

in temperature and blood pressure with paracetamol is interesting and must be kept in mind when treating patients with Hodgkin's disease who might require antipyretic drugs.My patient developed hypothermia and hypotension which seemed to be unrelated, as I mentioned, to any drug ingestion.The patient did not receive paracetamol, salicylate, or any similar drug prior to the drop of temperature and blood pressure, though 10 days earlier he had received a five-day course of ethambutol and isoniazid because a provisional diagnosis of sarcoidosis had been made.To my knowledge those two drugs have no thermoregulatory side effect, either alone or when given in combination.
Late Post-traumatic Headache
Authors: J. Cyriax
Journal: BMJ (1966)

Sections 5 8 and 59 of the Act are con- veniently quoted by Mrs. Jenkins.'The word " unlawfully " occurs six times, and became the main issue in R. v. Bourne, 1938, which established that abortion can be lawful and unlawful, only the latter being felonious.3That the Act is capable of being misinterpreted by jurists of the eminence of Rupert Cross (in a broadcast talk) is sufficient reason for restating the law, but only increases the need to restate the law accurately.A myth has been created that every time a surgeon performs an abortion the police turn a blind eye, much as they are expected to if he has left his car in the wrong place during the operation.It ought to be under- stood, once and for all, that abortion is an operation like any other operation: the law can neither compel a surgeon to perform it nor, provided his position is ethical, punish him for performing it.What needs changing is not the law but the myth.-Iam, etc.,
Deficient ileal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in sitosterolemia: Sitosterol is not a feedback inhibitor of intestinal cholesterol biosynthesis
Authors: Lien B. Nguyen, Gerald Salen, Sarah Shefer, John Bullock, Thomas Chen, G.Stephen Tint, Indu R. Chowdhary, Susan Lerner
Journal: Metabolism (1994)
Hypersensitivity Pneumonitis in Peat Moss Processing Plant Workers
Authors: YVON CORMIER, EVELYNE ISRAËL-ASSAYAG, GAÉTANE BÉDARD, CAROLINE DUCHAINE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A nonsmoking 54-yr-old man, employed in a peat moss packaging plant, developed dyspnea and recurrent fever. The diagnosis of hypersensitivity pneumonitis (HP) was made. Thirteen of 14 coworkers and 13 nonexposed control subjects were studied. Five workers were nonsmokers, two were minimal smokers, and six were smokers. HP was found in another subject. Monocillium sp. and Penicillium citreonigrum, 4.6 × 107 CFU/g, were found in the peat moss. Three nonsmokers, the two minimal smokers (including the subject with HP), and the index case had antibodies to these microorganisms; none of the six heavy smokers had antibodies. Serum TNF- α was higher in the workers than in the control subjects (0.930 ± 0.177 versus 0.350 ± 0.076). Three of the four asymptomatic seropositive workers and two seronegative smokers were further evaluated. All three seropositive workers had normal lung functions and CT but they all had a lymphocytic alveolitis (30, 34, and 68% lymphocytes in their bronchoalveolar lavage [BAL]). The smokers had normal lung functions, CT, and percentage of BAL lymphocytes (3 and 13%). This study identified a previously unrecognized work environment that can lead to HP and documented a protective effect of smoking on the response to antigens.
Notch Signaling Regulates Platelet-Derived Growth Factor Receptor-β Expression in Vascular Smooth Muscle Cells
Authors: Shaobo Jin, Emil M. Hansson, Saara Tikka, Fredrik Lanner, Cecilia Sahlgren, Filip Farnebo, Marc Baumann, Hannu Kalimo, Urban Lendahl
Journal: Circulation Research (2008)

Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor ( PDGFR )-β is a novel immediate Notch target gene. PDGFR -β expression was upregulated by Notch ligand induction or by activated forms of the Notch receptor. Moreover, upregulation of PDGFR -β expression in response to Notch activation critically required the Notch signal integrator CSL. In primary VSMCs, PDGFR -β expression was robustly upregulated by Notch signaling, leading to an augmented intracellular response to PDGF stimulation. In newborn Notch3 -deficient mice, PDGFR-β expression was strongly reduced in the VSMCs that later develop an aberrant morphology. In keeping with this, PDGFR-β upregulation in response to Notch activation was reduced also in Notch3 -deficient embryonic stem cells. Finally, in VSMCs from a CADASIL patient carrying a NOTCH3 missense mutation, upregulation of PDGFR -β mRNA and protein in response to ligand-induced Notch activation was significantly reduced. In sum, these data reveal a hierarchy for 2 important signaling systems, Notch and PDGF, in the vasculature and provide insights into how dysregulated Notch signaling perturbs VSMC differentiation and function.
Availability of energetic substrates and exercise performance in heart failure with or without diabetes
Authors: Vojtech Melenovsky, Martin Kotrc, Jan Polak, Terezie Pelikanova, Bela Bendlova, Monika Cahova, Ivan Malek, Petr Jarolim, Ludmila Kazdova, Josef Kautzner
Journal: European Journal of Heart Failure (2012)
Reduced cardiovascular sympathetic excitatory responses during iloprost infusion in conscious dogs
Authors: O. Rimoldi, S. Pierini, M. R. Pagani, M. Pagani
Journal: Cardiovascular Research (1991)

Study objective — The aim was to determine the effects of the stable prostacyclin analogue iloprost (ZK 36374) on systemic haemodynamics and on cardiovascular neural control. Design — The buffering effect was examined of intravenous and intracoronary iloprost infusion on the excitatory sympathetic reflexes elicited from the heart by (1) intracoronary injections of bradykinin and (2) transient coronary artery occlusion. Subjects — 22 conscious mongrel dogs of either sex, weight 20-25 kg, were used. Measurements and main results — ECG, systemic arterial pressure, left atrial pressure, and left ventricular pressure and contractility (dP/dt) were continuously monitored for the duration of the experiments. Iloprost infusion reduced left ventricular pressure, mean arterial pressure, and dP/dt without causing significant changes in heart rate. Transient non-hypertensive coronary artery occlusion increased heart rate and depressed contractility. During intravenous iloprost infusion, coronary artery occlusion no longer elicited an increase in heart rate, while left ventricular dP/dt was more drastically reduced. This pattern of response was not substantially modified by β adrenergic blockade, whereas the blockade of muscarinic receptors with atropine was accompanied by hypotension and a greater reduction of dP/dt. The observation of a reduced pressor response to the intracoronary injections of bradykinin during iloprost administration further indicated a restraining effect of iloprost on the sympathetic reflexes elicited from the heart. Conclusions — The data suggest the hypothesis that the protective effects on the ischaemic myocardium observed with iloprost infusions may arise not only from its vasodilator and antiplatelet properties, but also from its capacity to blunt excitatory sympathetic reflexes.