tbuckley/cabot-search huggingface dataset:
Abstract 8912: Pinch Proteins Are Essential for Cardiac Protein Kinase B Signaling
Authors: Karen S Frese, Benjamin Meder, Farbod Sedaghat-Hamedani, Inken G Huttner, Hugo A Katus, Wolfgang Rottbauer
Journal: Circulation (2011)

Integrin-linked kinase (ILK) is essential for cell maturation, migration and proper adhesion of the cardiac intercalated disks and costameres. It furthermore is as an essential component of the cardiac mechanical stretch sensor. Until now, the precise molecular function of ILK and its associated interaction partners are still unknown. To assess the cardiac function of ILK interacting PINCH proteins, we used a reverse genetics approach in zebrafish to identify and deplete the orthologs PINCH1 and PINCH2 by injection of morpholino antisense oligonucleotides. Depletion of either PINCH isoforms independently leads to instability of the ILK-PINCH-Parvin complex, loss of stretch-responsive gene expression and progressive heart failure. The impaired cardiac function in PINCH-deficient embryos can be explained by loss of Protein kinase B activity, since Akt/PKB phosphorylation at Serine 473 is significantly reduced in PINCH-morphants and overexpression of constitutively active PKB reconstitutes their cardiac function to almost normal values. Our data demonstrate an important role of PINCH proteins in maintaining cardiac contractility by stabilizing the IPP complex and thereby regulating Akt/PKB activity in the vertebrate heart.
Abstract 4429: Toxicology and drug delivery by novel cucurbit[n]uril-type nanocontainers
Authors: Gaya Hettiarachchi, Da Ma, Duc Nguyen, Lyle Isaacs, Volker Briken
Journal: Cancer Research (2011)

Abstract Many drug delivery systems are based on the ability of certain macrocyclic compounds – such as cyclodextrins – to act as molecular containers for pharmaceutical agents in water. Cucurbit[n]urils (CB[n]) are a class of molecular containers that bind to a variety of cationic and neutral species with high affinity and therefore show great promise as a drug delivery system. We hypothesized that these nanocontainers can be used to increase solubility of hydrophobic small chemical compound drugs. In this study we investigated the toxicology, uptake, and bioactivity of two cucurbit[n]urils CB[n]-type containers (named Motor1 and Motor2). Both containers induced no toxicity at concentrations of up to 1 mM in human cell lines originating from kidney, liver or blood tissue using assays for metabolic activity and cytotoxicity. Furthermore, the Motor1 container was tolerated in mice without any toxicity after intravenous dosing of up to 1.5g/kg bodyweight. Interestingly, Motor1 was able to bind the cancer drug paclitaxel and increase its solubility in water by a factor of 2000. Motor2 demonstrated an increase of water solubility of camptothecin by 500fold. Finally, bioactivity assays showed that the increase in solubility by paclitaxel via Motor1 led to a more efficient killing of the ovarian cancer cell line SKOV-3. In conclusion, our study reveals very low toxicity of two novel members of the cucurbit[n]uril family of nanocontainers. It demonstrates the increase in solubility of two important cancer drugs by the containers which led to increased killing of cancer cells in vitro. These results provide initial proof-of-concept towards the use of CB[n] molecular containers as an advanced drug delivery system. 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 4429. doi:10.1158/1538-7445.AM2011-4429
Abstract 1620: Deregulation of cohesion establishment factor DCC1 promotes colorectal cancer cell growth
Authors: Kiyoshi Yamaguchi, Yusuke Nakamura, Yoichi Furukawa
Journal: Cancer Research (2010)

Abstract Defective in sister chromatid cohesion 1 homolog (dcc1) was identified as a member of alternative replication factor C complex in yeast. Dcc1 has been known to play a crucial role in chromatid cohesion together with other subunits (ctf18 and ctf8), and that it is essential for DNA replication in yeast. We previously carried out genome-wide expression profile analysis of human colorectal tumors using cDNA microarray, and identified a set of genes whose expression was deregulated in tumor cells. In this study, we focused on human DCC1, because its expression was frequently up-regulated in the majority of colorectal cancer tissues. Quantitative PCR analysis corroborated its elevated expression in 12 of additional 20 colorectal tumors compared to their matched non-cancerous colonic mucosa. To examine whether DCC1 is involved in proliferation of cancer cells, we generated small interfering RNAs (siRNAs) targeting human DCC1. Notably, treatment of colorectal cancer cells with DCC1-specific siRNAs significantly suppressed their proliferation, suggesting that its elevated expression is essential for the growth of colorectal cancer cells. To clarify the mechanism of its overexpression, we carried out a reporter assay using 1-kb of its 5’-flanking region and 5’-UTR. As a result, we found that a region between −10 and +70 of transcription starting site was responsible for the activity, and identified three putative E2F1-binding sequences within this region. Further analysis revealed that the three motifs regulate the promoter activity. These data suggests that deregulated E2F1-signaling may play a role in the proliferation of cancer cells in part through the increased DCC1 expression, and that DCC1 may serve a target molecule for the development of new anti-cancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1620.
The Influence of Cholestyramine on Thyroxine Absorption
Authors: Robert C. Northcutt
Journal: JAMA (1969)

Cholestyramine resin, an anionic exchange resin, currently being investigated as an agent for lowering serum cholesterol levels, has been shown to interfere with the absorption of ingested thyroid hormone. A small quantity of the resin is capable of binding thyroxine under the conditions encountered in the gastrointestinal tract. Interference with thyroid hormone absorption by cholestyramine can be minimized by allowing a time interval of at least four hours between the ingestion of the two agents. Hypothyroid patients receiving cholestyramine should be examined periodically for evidence of hypothyroidism, and adjustments in dose and time interval between the two agents should be made if malabsorption of thyroid hormone is significant.
Increase in Suicidal Thoughts and Tendencies
Authors: Hewitt F. Ryan
Journal: JAMA (1968)

Seven cases occurred in which there was an association in time between the institution of diazepam therapy and the onset of suicidal thoughts and tendencies, which tended to be concealed by patients who were at the time receiving psychiatric treatment. An additional patient demonstrated deepening of depression while receiving diazepam. Physicians should consider the possible adverse depressive effect of diazepam when prescribing it as an antianxiety agent.
DIRECTIONS FOR USING DRIED MILK
Authors: H. Leader
Journal: BMJ (1920)

<h3>ABSTRACT</h3> Biomarkers to assess the severity of acute respiratory syncytial virus (RSV) infection are needed. We conducted a meta-analysis of 490 unique profiles from six public RSV blood transcriptome datasets. A repertoire of 382 well-characterized transcriptional modules was used to define dominant host responses to RSV infection. The consolidated RSV cohort was stratified according to four traits: “interferon response” (IFN), “neutrophil-driven inflammation” (Infl), “cell cycle” (CC), and “erythrocytes” (Ery). Eight prevalent blood transcriptome phenotypes were thus identified. Among those three Ery+ phenotypes comprised higher proportions of patients requiring intensive care. We posit that the erythrocyte module is linked to an overabundance of immunosuppressive erythroid cells that might underlie progression to severe RSV infection. These findings outline potential priority areas for biomarker development and investigations into the immune biology of RSV infection. The approach that was employed here will also permit to delineate prevalent blood transcriptome phenotypes in other settings.
Treatment of hypercalcaemia in sarcoidosis with flurbiprofen.
Authors: T Littlewood, A Hunter, P Beck, P J Heyburn, R C Brown
Journal: BMJ (1983)

Accuracy of insulin injection in elderly patientsGood control of diabetes depends on the patient being capable of consistently injecting accurate amounts of insulin.Problems with self administration of insulin might be expected in patients suffering from confusion or impaired vision or coordination.Thus older diabetic patients might be at particular risk from errors in the amounts of insulin injected.We investigated this hypothesis and the possible merits of different insulin syringes.
Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P2 and PtdIns(3,4,5)P3 promotes immunity to mycobacteria
Authors: Sangeeta Tiwari, Han-Pil Choi, Takeshi Matsuzawa, Marc Pypaert, John D MacMicking
Journal: Nature Immunology (2009)
Ecologists and ecologians
Authors: S. Vaisrub
Journal: JAMA (1971)

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
Effect of food intake during labour on obstetric outcome: randomised controlled trial
Authors: G. O'Sullivan, B. Liu, D. Hart, P. Seed, A. Shennan
Journal: BMJ (2009)

<b>Objective</b> To investigate the effect of feeding during labour on obstetric and neonatal outcomes. <b>Design</b> Prospective randomised controlled trial. <b>Setting</b> Birth centre in London teaching hospital. <b>Participants</b> 2426 nulliparous, non-diabetic women at term, with a singleton cephalic presenting fetus and in labour with a cervical dilatation of less than 6 cm. <b>Intervention</b> Consumption of a light diet or water during labour. <b>Main outcome measures</b> The primary outcome measure was spontaneous vaginal delivery rate. Other outcomes measured included duration of labour, need for augmentation of labour, instrumental and caesarean delivery rates, incidence of vomiting, and neonatal outcome. <b>Results</b> The spontaneous vaginal delivery rate was the same in both groups (44%; relative risk 0.99, 95% confidence interval 0.90 to 1.08). No clinically important differences were found in the duration of labour (geometric mean: eating, 597 min <i>v</i> water, 612 min; ratio of geometric means 0.98, 95% confidence interval 0.93 to 1.03), the caesarean delivery rate (30% <i>v</i> 30%; relative risk 0.99, 0.87 to 1.12), or the incidence of vomiting (35% <i>v</i> 34%; relative risk 1.05, 0.9 to 1.2). Neonatal outcomes were also similar. <b>Conclusions</b> Consumption of a light diet during labour did not influence obstetric or neonatal outcomes in participants, nor did it increase the incidence of vomiting. Women who are allowed to eat in labour have similar lengths of labour and operative delivery rates to those allowed water only. <b>Trial registration</b> Current Controlled Trials ISRCTN33298015.
Choice of Opportunities in Medicine
Authors: James Howard Means
Journal: New England Journal of Medicine (1954)

To the young man or woman who has just earned the degree of doctor of medicine a rich spectrum of opportunity presents itself. As some years earlier the choice of medicine as a career had to be made, so now again a choice has to be made—this time that of what area of medicine the young doctor shall enter. No longer can anyone encompass it all. Some may select a relatively wide portion of the spectrum, others may focus sharply on one of its narrower bands, but never should any of them let the light of the whole fade entirely . . .
RETRO-PHARYNGEAL ABSCESS—-WITH REPORT OF CASE.
Authors: REVERE H. HERROLD
Journal: JAMA (1894)

Miss T; age, 22; native of Sweden; occupation, clerk; left the land of her nativity in August, 1893, in good health as far as can be discovered. August 29 I saw her for the first time, and received a history of previous good health, except that a week before, she was seized with choking andpharyngeal spasms. These symptoms passed away and none appeared again until the day of my visit, when I found the spasms and choking present, with cyanosis, greatly increased during the pharyngeal spasms. Examination of the throat with the finger revealed no pathologic condition, leaving thus a doubt as to what caused the spasms and choking. Anti-spasmodics were administered, which only partially relieved. The patient having stated that no passage from the bowels had occurred for several days, a cathartic was prescribed and the patient left for a time. In less than an hour I was again
Intramyocardial pressure and distribution of coronary blood flow during systole and diastole in the horse
Authors: R. L HAMLIN, M. J LEVESQUE, M. D KITTLESON
Journal: Cardiovascular Research (1982)

Transmural myocardial blood flow was measured with microspheres in systole and in diastole, along with intramyocardial pressure, in seven anaesthetised horses. Intramyocardial pressures were measured with a miniature manometer implanted in the tip of a 16-gauge needle. Peak systolic intramyocardial pressure decreased from subendocardium to subepicardium and never exceeded intraventricular pressure. Systolic blood flow decreased from epicardium to endocardium where it did not differ from zero. Diastolic blood flow increased from epicardium to subendocardium, but then decreased in the most endocardial layer to a level not different from the immediate subepicardial layer. The horse was a useful model for studying these parameters because the ventricular walls are so thick and the heart rate is so slow that injections may be made during various phases of the cardiac cycle. These results of transmural myocardial blood flow and intramyocardial pressure measured in the same animal are identical with those of others, except for the reduction in subendocardial blood flow compared with the layers just epicardial to that.
Abnormal serum free light chain ratio in patients with multiple myeloma in complete remission has strong association with the presence of oligoclonal bands: implications for stringent complete remission definition
Authors: Carlos Fernández de Larrea, María Teresa Cibeira, Montserrat Elena, Juan Ignacio Arostegui, Laura Rosiñol, Montserrat Rovira, Xavier Filella, Jordi Yagüe, Joan Bladé
Journal: Blood (2009)
Aspirin and Reye's Syndrome-Reply
Authors: Thomas J. Halpin
Journal: JAMA (1983)

In Reply.—  The Ohio Department of Health received only two reports of Reye's syndrome cases from the Cleveland Clinic during the study period (December 1978 through March 1980). The first of the two cases reported to us was not included in the study because our nurse coordinator could not get timely access to the child's record to verify fulfillment of the case definition. This child was reported by Dr Orlowski to have received aspirin. The other patient who was included in our study did not have a history of aspirin ingestion.  Thirty-three hospitals reported cases to the Ohio Department of Health. With the exception of Dr Orlowski, there is no evidence of similar reporting problems at the other 32 hospitals. The vast majority of cases (85% ) of the 227 cases were reported from the state's six major pediatric referral centers. In Cleveland, this was Rainbow Babies and Children's Hospital (affiliated
Transforming growth factor β<sub>1</sub>induces the expression of α1(i) procollagen mRNA by a hydrogen peroxide-C/EBPβ-dependent mechanism in rat hepatic stellate cells
Authors: Elena R. García-Trevijano, María J. Iraburu, Luis Fontana, José A. Domínguez-Rosales, Anitra Auster, Amador Covarrubias-Pinedo, Marcos Rojkind
Journal: Hepatology (1999)

Oxidative stress plays a key role in liver fibrosis. Both inflammatory cells and activated Kupffer cells produce H2O2, an oxidant involved in the activation of hepatic stellate cells (HSC). Increased production of reactive oxygen intermediates (ROIs) in fibrotic livers is associated in part with the up-regulation of transforming growth factor beta (TGF-beta), and this cytokine enhances collagen production by cultured HSC. However, the possible link between oxidative stress and the molecular mechanisms by which TGF-beta induces collagen gene expression in HSC remains to be elucidated. To address this question, we investigated whether H2O2 is a mediator of TGF-beta-elicited alpha1(I) collagen gene (col1a1) up-regulation. We demonstrated that TGF-beta induces the accumulation of H2O2, and that this oxidant is, in turn, directly involved in up-regulating the expression of the col1a1 gene. While the addition of H2O2 to HSC induced the expression of alpha1(I) procollagen mRNA, catalase, an H2O2 enzyme scavenger, abrogated TGF-beta-mediated col1a1 gene up-regulation. We transfected HSC with chimeric plasmids driven by different segments of the mouse col1a1 promoter and mapped a cis-acting element (-370 to -344) essential for TGF-beta responsiveness. We further showed that TGF-beta induced the activation and binding of a C/EBPbeta-containing transcriptional complex to this sequence, an effect that was also mimicked by the addition of H2O2. Taken together, these data demonstrate a direct connection between TGF-beta-mediated accumulation of H2O2 and the up-regulation of col1a1 gene in HSC.
SOME EXPERIMENTS ON THE RELATION BETWEEN AUDITION AND THE CIRCULATION OF THE BLOOD IN THE HEAD.
Authors: HAMILTON STILLSON
Journal: JAMA (1900)

A year ago the writer had a period of fortunate misfortune. His left ear had for a time a slight tinnitus with slight lowering of hearing acuity. It enabled him to institute a series of simultaneous experiments on a normal and on an abnormal ear. He thus has been enabled on his own person to confirm or refute statements made by others concerning tinnitus and its allied states and to institute comparison between effects of similar causes in healthy and in unhealthy ears. This tinnitus, it should be stated, was caused by tubal edema. This is known not only by self-inspection of the pharyngeal orifice of the tubes, but by palpation, so to speak, of the tube by means of the tongue thrust into the post-nasal space. The writer is able to insert the tip of his tongue into the nasopharynx even to the vault of that cavity, and so
Improved Survival with T Cell Clonotype Stability After Anti–CTLA-4 Treatment in Cancer Patients
Authors: Edward Cha, Mark Klinger, Yafei Hou, Craig Cummings, Antoni Ribas, Malek Faham, Lawrence Fong
Journal: Science Translational Medicine (2014)

CTLA-4 blockade induces T cell repertoire turnover, but high-frequency clonotypes are maintained in patients with favorable outcomes.
Rontgen retrospective. One hundred years of a revolutionary technology
Authors: R. G. Evens
Journal: JAMA (1995)

ONE HUNDRED YEARS ago, on November 8, 1895, Wilhelm Conrad Rontgen made a startling discovery in his laboratory in Wurzburg, Germany. The physics professor was experimenting with the action of electric energy in partially evacuated glass tubes—a popular scientific activity in the last quarter of the 19th century. Meticulously laboring in a darkened laboratory with the electrically charged tube, he noticed a glow from the far corner of the room. This observation led to a series of experiments, and while passing his hand between a fluorescing screen and the tube, he was astonished to see what appeared to be the shadows of his bones.  It is impossible to know exactly what Rontgen thought at that moment. Most of the great technological inventions have been foreseen by dreamers who anticipated the discovery by prediction or fantasy. For example, people have always thought about flying—the airplane made these dreams reality. Physicians had
Hypertension: The Diverse Role of Electrolyte Intake
Authors: F C Luft, D A McCarron
Journal: Annual Review of Medicine (1991)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Targeting of the CNS in MPS-IH Using a Nonviral Transferrin-α-l-iduronidase Fusion Gene Product
Authors: Mark J Osborn, Ron T McElmurry, Brandon Peacock, Jakub Tolar, Bruce R Blazar
Journal: Molecular Therapy (2008)

Mucopolysaccharidosis type I (Hurler syndrome) is caused by a deficiency of the enzyme α-l-iduronidase (IDUA), and is characterized by widespread lysosomal glycosaminoglycan (GAG) accumulation. Successful treatment of central nervous system (CNS) diseases is limited by the presence of the blood-brain barrier, which prevents penetration of the therapeutic enzyme. Given that the brain capillary endothelial cells that form this barrier express high levels of the transferrin receptor (TfR), we hypothesized that the coupling of IDUA to transferrin (Tf) would facilitate IDUA delivery to the CNS. A plasmid bearing a fusion gene consisting of Tf and IDUA was constructed which, when delivered in vivo, resulted in the production of high levels of an enzymatically active protein that was transported into the CNS by TfR-mediated endocytosis. Short-term treatment resulted in a decrease in GAGs in the cerebellum of mucopolysaccharidosis type I (MPS I) mice. This approach, therefore, represents a potential strategy for the delivery of therapeutic enzyme to the CNS.
Disseminated epidermolytic acanthoma probably related to trauma
Authors: None Sánchez-Carpintero, None España, None Idoate
Journal: British Journal of Dermatology (1999)

Epidermolytic acanthoma is a rare benign tumour, which may occur in both isolated and disseminated forms. Only seven cases of disseminated epidermolytic acanthoma (DEA) have been described. This entity should be distinguished from other hereditary or acquired conditions which involve epidermolytic hyperkeratosis and other benign acanthomas. On the basis of the clinical history and the histological findings, we diagnosed a case of DEA which was probably secondary to repeated trauma.
Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment
Authors: V. Lokesh Battula, Ye Chen, Maria da Graca Cabreira, Vivian Ruvolo, Zhiqiang Wang, Wencai Ma, Sergej Konoplev, Elizabeth Shpall, Karen Lyons, Dirk Strunk, Carlos Bueso-Ramos, Richard Eric Davis, Marina Konopleva, Michael Andreeff
Journal: Blood (2013)