tbuckley/cabot-search huggingface dataset:
AZ703, an Imidazo[1,2-<i>a</i>]Pyridine Inhibitor of Cyclin-Dependent Kinases 1 and 2, Induces E2F-1-Dependent Apoptosis Enhanced by Depletion of Cyclin-Dependent Kinase 9
Authors: Dongpo Cai, Kate F. Byth, Geoffrey I. Shapiro
Journal: Cancer Research (2006)

Abstract Preclinical studies were performed of a novel selective imidazopyridine cyclin-dependent kinase (cdk) inhibitor, AZ703. In vitro kinase assays showed that IC50 values for AZ703 against purified cyclin E/cdk2 and cyclin B/cdk1 were 34 and 29 nmol/L, respectively. In contrast, the IC50 against cdk4 was &amp;gt;10 μmol/L. AZ703 also inhibited cdk7 and cdk9 with IC50 values of 2.1 μmol/L and 521 nmol/L, respectively. Treatment of U2OS, NCI-H1299, and A549 cells for 24 hours resulted in growth arrest involving multiple cell cycle phases. At low drug concentrations (&amp;lt;2 μmol/L), G2 arrest predominated, whereas at higher concentrations (≥2 μmol/L), S-G2 arrest was observed. When cells were synchronized in G1 by starvation and released into AZ703, a block in G1 occurred that was not evident in exponentially growing cells. Cell cycle arrest was associated with reduced phosphorylation of the retinoblastoma protein and p27Kip1 at cdk2 phospho-sites. Following longer exposures, apoptosis was evident. Cells were further sensitized to AZ703 following recruitment to S phase by synchronization. Consistent with the inhibition of cdks during S and G2 that modulate the activity and stability of E2F-1, AZ703 treatment induced E2F-1 expression. In U2OS and NCI-H1299 cells engineered to inducibly express the dominant-negative mutant E2F-1 (1-374), expression of the mutant decreased AZ703-mediated apoptosis, indicating dependence on E2F-1 transcriptional targets. AZ703-induced apoptosis in NCI-H1299 cells was enhanced by small interfering RNA–mediated depletion of cdk9, which caused reduced levels of Mcl-1 and XIAP, suggesting that cdk2, cdk1, and cdk9 represent a rational subset of family members for drug targeting. (Cancer Res 2006; 66(1): 435-44)
Evaluation and Management of the Patient With Syncope
Authors: Wishwa N. Kapoor
Journal: JAMA (1992)

To review the studies on diagnostic evaluation of syncope and to provide an approach to the diagnostic testing and management of this condition.Published studies on the evaluation of syncope in the English language.Cohort studies and case series of patients presenting with syncope and focused studies of various diagnostic tests such as prolonged electrocardiographic monitoring, electrophysiologic studies, and upright tilt testing. Specific selection criteria were used in the case of prolonged electrocardiographic monitoring, in which all studies had to have performed at least 12 hours of monitoring.Studies reviewed by the author.Studies in the 1980s have shown that a cause of syncope is not diagnosed in as many as 47% of the patients presenting with this symptom. When a cause of syncope is established, a history and physical examination lead to the identification of 56% to 85% of the causes. In the remaining patients, arrhythmia detection is a central issue. A major problem with the use of ambulatory electrocardiographic (Holter) monitoring in the diagnosis of arrhythmias is that symptomatic correlation with arrhythmias is rarely found (only 4% of patients). Increasing the duration of monitoring from 24 to 72 hours does not lead to increased yield of symptomatic arrhythmias. Patient-activated intermittent loop recorders that can be worn for several weeks may occasionally show a symptomatic correlation, but they are most useful in patients with multiple recurrences of syncope. Electrophysiologic studies are more likely to be abnormal in patients with underlying heart disease or those who have abnormalities on surface electrocardiogram. The most common abnormality found on electrophysiologic studies is inducible ventricular tachycardia. Upright tilt testing has been used to induce vasovagal syncope in patients with syncope of unknown cause. A positive response has been found in 26% to 87% of patients undergoing this type of testing. The specificity of this test needs to be further investigated. In patients with recurrent syncope of unknown cause, psychiatric evaluation should also be pursued for illnesses such as generalized anxiety disorder, panic disorder, somatization, and major depression.A directed approach to the evaluation is possible using the studies on diagnostic testing of syncope.
An insulin-induced DNA-binding protein for the human growth hormone gene.
Authors: D Prager, S Gebremedhin, S Melmed
Journal: Journal of Clinical Investigation (1990)

The control of gene transcription is usually mediated by transacting transcriptional factors that bind to upstream regulatory elements. As insulin regulates transcription of the growth hormone (GH) gene, we tested nuclear extracts from unstimulated and insulin-stimulated Chinese hamster ovarian (CHO) cells for binding to four human GH (hGH) gene promoter oligonucleotide fragments identified as target-binding sequences by DNAse I footprinting. Using a mobility shift assay, an insulin-induced DNA-binding protein was identified. This protein binds to two upstream overlapping oligonucleotide sequences. Binding activity is present at low levels in unstimulated CHO cells and is stimulated by insulin treatment with a time course suggesting that protein synthesis is required. Incubation of the cells with cycloheximide and puromycin confirmed that de novo protein synthesis is necessary for the increased binding activity. Competition with excess unlabeled specific competitor oligonucleotides prevented binding, while unrelated similar-sized oligonucleotides failed to compete for binding, indicating that the observed DNA-protein complex formation is specific. A protein of approximately 70-80 kD was detected by gradient gel electrophoresis. In conclusion, insulin-mediated DNA-protein binding has been identified on the upstream hGH promoter, suggesting a trans-active role for insulin in mediating polypeptide hormone gene expression.
Changes in Regional Brain Glucose Metabolism Measured With Positron Emission Tomography After Paroxetine Treatment of Major Depression
Authors: Sidney H. Kennedy, Kenneth R. Evans, Stephanie Krüger, Helen S. Mayberg, Jeffrey H. Meyer, Sonia McCann, Andrew I. Arifuzzman, Sylvain Houle, Franco J. Vaccarino
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Depression is commonly associated with frontal hypometabolic activity accompanied by hypermetabolism in certain limbic regions. It is unclear whether successful antidepressant treatments reverse these abnormalities or create new resting levels of metabolism. The aim of the present study was to assess the effects of successful paroxetine treatment on regional glucose metabolism in patients with major depression. METHOD: Positron emission tomography with [18F]fluorodeoxyglucose was performed on 13 male patients before and after 6 weeks of paroxetine therapy. Resting state scans were also acquired under similar conditions in 24 healthy male subjects for comparison. RESULTS: After successful paroxetine therapy, increased glucose metabolism occurred in dorsolateral, ventrolateral, and medial aspects of the prefrontal cortex (left greater than right), parietal cortex, and dorsal anterior cingulate. Areas of decreased metabolism were noted in both anterior and posterior insular regions (left) as well as right hippocampal and parahippocampal regions. In comparison to metabolism levels in a group of healthy volunteers, the increase in prefrontal metabolic activity represented a normalization of previously reduced metabolic activity, whereas the reduction in pregenual anterior cingulate activity represented a decrease from previously elevated metabolic levels. CONCLUSIONS: These results provide further support for a dysfunction in cortical-limbic circuitry in depression, which is at least partly reversed after successful paroxetine treatment.
Lineage-Specific Modulation of Interleukin 4 Signaling by Interferon Regulatory Factor 4
Authors: Sanjay Gupta, Man Jiang, Alissa Anthony, Alessandra B. Pernis
Journal: The Journal of Experimental Medicine (1999)

Interleukin (IL)-4 is an immunoregulatory cytokine that exerts distinct biological activities on different cell types. Our studies indicate that interferon regulatory factor (IRF)-4 is both a target and a modulator of the IL-4 signaling cascade. IRF-4 expression is strongly upregulated upon costimulation of B cells with CD40 and IL-4. Furthermore, we find that IRF-4 can interact with signal transducer and activator of transcription (Stat)6 and drive the expression of IL-4–inducible genes. The transactivating ability of IRF-4 is blocked by the repressor factor BCL-6. Since expression of IRF-4 is mostly confined to lymphoid cells, these data provide a potential mechanism by which IL-4–inducible genes can be regulated in a lineage-specific manner.
Shyness, Social Anxiety, and Impaired Self-esteem in Turner Syndrome and Premature Ovarian Failure
Authors: Peter J. Schmidt, Graca M. P. Cardoso, Judith L. Ross, Nazli Haq, David R. Rubinow, Carolyn A. Bondy
Journal: JAMA (2006)

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
Control of the Hydrogen Ion
Authors: Halvor N. Christensen
Journal: New England Journal of Medicine (1952)

SOME unfortunate awkwardness of terminology has been associated with the heritage of information and ideas in the field of physiologic neutrality regulation. One relatively simple misconception seems to lie behind most of the trouble: when a weak acid HA dissociates, this has been interpreted erroneously as a combining of A- with a cation B+, rather than the breaking of the combination between H+ and A-. Almost everyone is familiar with the difference in the relations that sodium and hydrogen bear to the rest of the molecule in simple structures like NaHCO3 and H2CO3; . . .
A TONSIL EXPRESSOR
Authors: Julius H. Hess
Journal: JAMA (1918)

Examination of the teeth and tonsils in a large series of cases of endocarditis, rheumatism and chorea has demonstrated that many of the patients are suffering from alveolar abscesses and infected tonsils. The removal of such teeth is a simple matter even during the course of the disease, but only a few men have had the temerity to advise tonsillectomy at the height of the infection in acute cardiac conditions. Believing that much could be accomplished by evacuating the pus which has accumulated in the tonsils in many of these cases by expression and massage of the tonsils, I have devised an instrument which has been found of practical value in our cardiovascular and rheumatic wards for diagnostic purposes and frequently for treatment. Set at right angles to a 7½-inch steel handle is a cross-piece of steel three-quarters inch in length and three-sixteenths inch in diameter, well rounded on all
Pertussis Vaccine Encephalopathy-Reply
Authors: James D. Cherry
Journal: JAMA (1990)

In Reply.—  The letters of Lewis, Menkes, Garbitelli, and Tilelli and Manniello all contain errors of fact and reasoning and seem to be aimed at preserving the myth of pertussis vaccine encephalopathy. Dr Menkes implies that in my assessment of the National Childhood Encephalopathy Study I focused on one set of biases. This is not true. Even though there clearly were biases that tended to exaggerate the calculated risks, the original data alone do not indicate a cause-and-effect relationship but only the redistribution of events over time. 1 If you believe that the increased number of vaccinations in cases during the 0- to 3-day period indicates a causative effect of vaccine, then by the same reasoning you must believe that the increased number of vaccinations in the controls during the rest of the observation period was protective against disease.  Since after considerable study there is no epidemiologic evidence that supports
Trends in prenatal screening for and diagnosis of Down's syndrome: England and Wales, 1989-97
Authors: D. Mutton, R. G Ide, E. Alberman
Journal: BMJ (1998)

The National Down Syndrome Cytogenetic Register holds data on 10651 cases of prenatally or postnatally diagnosed Down's syndrome occurring in England and Wales from 1 January 1989 to 31 December 1997 (93% of all eligible cases) (J Morris, personal communication). We used these data to investigate the trends in prenatal diagnosis of Down's syndrome between 1989 and 1997.

All clinical cytogenetic laboratories in England and Wales notify the register anonymously of trisomy 21 or related karyotypes, together with the date, place of and indications for referral, parental age, and family history. Most send a copy of the notification to the referring physician for confirmation and completion.1 The outcome of the pregnancy is requested for all cases diagnosed prenatally (but may not be known for several months) and is known for 91% of registered prenatal diagnoses overall.

In 1989 registrations numbered 1081; in 1993, 1144; and in 1997, 1336 (table). In contrast, …
Abstract 4808: Detection of aberrant DNA methylation in saliva samples as a predictor of recurrence in head and neck squamous cell carcinoma patients
Authors: Ana Carolina de Carvalho, Marianna M. Rettori, Danielle C. C. Maia, Andre L. Carvalho, Luiz P. Kowalski, Andre L. Vettore
Journal: Cancer Research (2011)

Abstract Aberrant DNA methylation (hypermethylation) at CpG islands within promoter regions is an epigenetic mechanism involved in the transcriptional silencing of several tumor suppressor genes. The presence of hypermethylation is commonly reported in different human cancers and might be useful as a molecular marker for tumor cell detection and for early detection of tumor recurrence. Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer and the lack of early detection and the high incidence of locoregional recurrence lead to high mortality rates. Therefore, the identification of new molecular markers to be used as diagnostic and prognostic indicators is of paramount importance in reducing these recurrence rates. The aim of this study was to evaluate promoter hypermethylation of tumor suppressor genes using Quantitative Methylation-Specific PCR (Q-MSP) in tumor and salivary rinse samples as a mean to detect epigenetic alterations specific to HNSCC. Tumor samples were collected from 150 patients at the time of surgery while salivary rinses were collected before and after the last curative treatment and during the follow up (every 6 months for 2 years). The hypermethylation profile of 24 genes was analyzed and allowed the selection of a panel of 5 specific and sensitive genes. At least one of these genes was found methylated in 61% of the salivary rinse samples collected before treatment, suggesting that this panel could be useful as a diagnostic tool. Patients harboring aberrant DNA methylation of these genes in the post-treatment salivary rinse showed worse 3-year overall survival (p=0.035) and 3-year free from local recurrence survival (p=0.043). Thus, our results support the idea that the evaluation of gene methylation profile in saliva, a non-invasive method of sample collection, could be a good prognostic indicator of HNSCC recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4808. doi:10.1158/1538-7445.AM2011-4808
Nation's Expenditures for Alcohol, Other Drugs, in Terms of Therapy, Prevention, Now Exceed $1.6 Billion
Authors: Phil Gunby
Journal: JAMA (1987)

ONE-YEAR EXPENDITURES in the United States for alcohol and other drug abuse treatment and prevention services total more than $1.6 billion.  That is the figure cited in the annual report (for the 1986 bookkeeping year) of the National Association of State Alcohol and Drug Abuse Directors, Inc. This is a not-for-profit organization, located in Washington, DC, whose members are officials designated by the state governors to administer publicly funded alcohol and other drug abuse treatment and prevention systems.  Since September 1984, the association has held a contract with the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism to provide data to the Alcohol, Drug Abuse, and Mental Health Administration. (See From the Alcohol, Drug Abuse, and Mental Health Administration, p 2029.)  Information in the latest report is from all 50 states, the District of Columbia, American Samoa, Puerto Rico, and the Virgin Islands. Highlights include
Macrocytosis and Leukopenia in Down's Syndrome
Authors: Kathryn Akin
Journal: JAMA (1988)

<h3>To the Editor.</h3> —On routine screening, we found that our adult patients with Down's syndrome had increased mean corpuscular volumes (MCVs), with normal hemoglobin values and hematocrits. Although first described in 1965,<sup>1</sup>mention of the abnormality has been limited mostly to the European literature and has not been included in recent reviews.<sup>2</sup> <h3>Study.</h3> —Fifteen patients with clinically diagnosed Down's syndrome were eligible for study. A control population was composed of other mentally retarded participants who attended the same educational facility. Patients and control subjects were matched for institutionalized status, age, sex, race, and IQ. Each of the patients with Down's syndrome underwent a history and physical examination, a complete blood cell count, thyroid function tests, and measurement of serum B<sub>12</sub>and folate levels. Intelligence quotient, diagnoses, pertinent history, and a complete blood cell count were collected for control subjects. The study population had a mean MCV of
Stedman's Electronic Medical Dictionary
Authors: Eytan Z. Blumenthal
Journal: JAMA (1997)

We still remember our first encounter as medical students with the intimidating vocabulary of medicine—not only Latin words, which seemed incomprehensible, but, even worse, terms commemorating prominent past figures. (What, exactly, is "anti-Trendelenburg?") We also recall the sense of relief when, after some delay, we purchased our first medical dictionaries, which we still use to this very day. Stedman's Electronic Medical Dictionary contains the entire text of the 26th edition of<i>Stedman's Medical Dictionary</i>(book version). Unfortunately, the illustrations are omitted from the electronic version. After quick and simple installation of the software, one is presented with a self-explanatory search screen. Besides the straightforward word search, searching options also include Boolean operators (AND, OR, NOT), "Browse on index" (useful when looking up long terms or when the precise spelling is unknown), and "Previous" and "Next" entry. The useful "History" (log-file) feature brings up a list of all previously searched
Early Lyme Disease
Authors: Gary P. Wormser
Journal: New England Journal of Medicine (2006)

A 26-year-old woman with a summer home on Long Island, New York, had a low-grade fever, malaise, arthralgias, headache, and neck pain one week after removing a tick from her thigh. Examination reveals a nontender oval (8 by 12 cm), homogeneously erythematous lesion at the site of the tick bite, consistent with erythema migrans. How should this case be managed? What if she had presented earlier, just after removing the tick?
Systematic Reviews of Diagnostic Test Accuracy
Authors: Mariska M.G. Leeflang, Jonathan J. Deeks, Constantine Gatsonis, Patrick M.M. Bossuyt
Journal: Annals of Internal Medicine (2008)

More and more systematic reviews of diagnostic test accuracy studies are being published, but they can be methodologically challenging. In this paper, the authors present some of the recent developments in the methodology for conducting systematic reviews of diagnostic test accuracy studies. Restrictive electronic search filters are discouraged, as is the use of summary quality scores. Methods for meta-analysis should take into account the paired nature of the estimates and their dependence on threshold. Authors of these reviews are advised to use the hierarchical summary receiver-operating characteristic or the bivariate model for the data analysis. Challenges that remain are the poor reporting of original diagnostic test accuracy studies and difficulties with the interpretation of the results of diagnostic test accuracy research.
Milestones in the discovery of antiviral agents: nucleosides and nucleotides
Authors: Erik de Clercq
Journal: Acta Pharmaceutica Sinica B (2012)

In this review article, a number of milestones in the antiviral research field on nucleosides and nucleotides are reviewed in which the author played a significant part, especially in the initial stages of their development. Highlighted are the amino acyl esters of acyclovir, particularly valacyclovir (VACV), brivudin (BVDU) and the valine ester of Cf1743 (FV-100), the 2′,3′-dideoxynucleosides (nucleoside reverse transcriptase inhibitors, NRTIs), the acyclic nucleoside phosphonates (S)-HPMPA, (S)-HPMPC (cidofovir) and alkoxyalkyl esters thereof (HDP-, ODE-CDV), adefovir and adefovir dipivoxil, tenofovir and tenofovir disoproxil fumarate (TDF), combinations containing TDF and emtricitabine, i.e., Truvada®, Atripla®, Complera®/Eviplera® and the Quad pill, and the phosphonoamidate derivatives GS-7340, GS-9131, GS-9191 and GS-9219.
Increased thrombosis incidence in a family with an inherited protein S deficiency and a high oxygen affinity hemoglobin variant
Authors: M. Berruyer, A. Francina, P. Ffrench, C. Negrier, B. Boneu, M. Dechavanne
Journal: American Journal of Hematology (1994)

Inherited protein S deficiency and the presence of a rare high oxygen affinity hemoglobin variant: Hb Rainier [beta 145 (HC2) Tyr-->Cys] were found in a family. Among 16 studied members, nine were found as carriers of protein S deficiency (type I with decrease of total, free, and activity levels). Six subjects carried the high-affinity hemoglobin variant, which displayed an increase of blood viscosity. Four members combined both abnormalities. Three had thrombotic accidents before the age of 30. We suggest the combination of protein S deficiency and the presence of this hemoglobin variant can lead to a severe primary hypercoagulable state with pathological consequences compared to each genetic defect alone.
The Physician and the Hospital
Authors: Ray E. Brown
Journal: New England Journal of Medicine (1971)

DR. Creditor's article, "If the Doctors Owned the Hospitals," accurately describes many of the inconsistencies in the governance of the hospital that are related to the place of the physician. Although the title to Dr. Creditor's article is tongue-in-cheek and not representative of the content, it does describe the sense of what many responsible leaders in the health field are advocating. This has to do with the advocacy of placing the doctor at risk through a capitation payment that includes hospitalization as well as the doctor's service. The notion is that the doctor would use less hospital care if he . . .