tbuckley/cabot-search huggingface dataset:
1229 GENOTYPIC AND PHENOTYPIC CHARACTERIZATION OF NS3 VARIANTS SELECTED IN HCV-INFECTED PATIENTS TREATED WITH ABT-450
Authors: T. Pilot-Matias, R. Tripathi, T. Dekhtyar, R. Menon, I. Gaultier, D. Cohen, T. Podsadecki, B. Bernstein, C. Collins
Journal: Journal of Hepatology (2011)
HEMATOGENOUS INFECTIONS OF THE SEMINAL DUCT
Authors: WILLIAM T. BELFIELD
Journal: JAMA (1925)

The frequency of gonococcus infections of the seminal duct has long dominated our conception of epididymitis and vesiculitis, which are commonly assumed to arise by invasion from the urethra only, and to interest merely urologists. That these organs are infected by parasites floating in the blood also has in recent years attained an importance demanding recognition by clinicians in general. Three items in the physiology of the seminal ducts are recalled: 1. The epididymis, which is by derivation the kidney of the cold-blooded animals (Fig. 1), may, like its successor the mammalian kidney, excrete the virus of the blood infections; epididymitis is a known feature of tuberculosis, syphilis, typhoid fever, malaria and influenza; and in the inflamed epididymis have been identified all the pathogenic organisms known to be excreted by the kidney. 2. The contents of the epididymis, abnormal as well as normal, pass through the vas deferens and accumulate
Natural autoantibodies reactive to glycosaminoglycans are disease state markers in rheumatoid arthritis and are associated with HLA
Authors: B Gyorgy, L Tothfalusi, G Nagy, M Pasztoi, P Geher, A Polgar, B Rojkovich, I Ujfalussy, P Misjak, A Koncz, E Pozsonyi, G Fust, A Falus, E I Buzas
Journal: Annals of the Rheumatic Diseases (2010)

Although natural autoantibodies make up the majority of circulating immunoglobulins, they have received little attention lately. This study examined systematic antibodies (Abs) reactive to glycosaminoglycans (GAGs), the carbohydrate components of proteoglycans that are released in large amounts from degrading cartilage.

To measure Abs reactive to six different types of GAGs, a specialised ELISA was used in which the carbohydrates were covalently linked to the plastic surface through a 2 nm spacer. Sera from rheumatoid arthritis patients (n=6), …
Abstract 2786: Potent inhibition of human liposarcoma cell growth and survival by novel modulators of the MDM2-p53 interaction
Authors: Yixiang Zhang, Stephen P. Remillard, George D. Demetri, Shaomeng Wang, Laurent Debussche, Andrew J. Wagner
Journal: Cancer Research (2012)

Abstract The tumor suppressor p53 is commonly inactivated in human malignancies. One mechanism is by genomic amplification and consequent overexpression of the ubiquitin E3 ligase MDM2, which targets p53 for proteosome-mediated degradation. The MDM2 gene is amplified in &amp;gt;95% of human liposarcomas, a disease for which the efficacy of systemic therapies is limited. Here, we compared the effects of two novel highly potent and selective inhibitors of the MDM2-p53 interaction, with the classic MDM2 inhibitor Nutlin-3 on the expression and activity of p53 and the resulting changes in human liposarcoma cell proliferation and survival. We determined MDM2 copy number, p53 mutational status, and relative expression levels of MDM2 and p53 proteins in 8 human liposarcoma cell lines and normal human preadipocytes/adipocytes. TP53 status was wild type in 7 of 8 liposarcoma cell lines, which also had genomic amplification of MDM2. MDM2 protein expression correlated with the degree of amplification and was highly expressed in comparison to normal preadipocytes/adipocytes. The two spiro-oxindole derivatives - Compounds A and B- (1) and Nutlin-3 were applied to liposarcoma cell lines with or without p53 siRNA and the biological consequences were determined by immunoblot, cell viability, cell cycle and apoptosis assays. Treatment with MDM2 inhibitors led to increased p53 protein levels and induction of its transcriptional targets MDM2 and p21. Cell viability was markedly decreased in a dose-dependent manner in liposarcoma cells with wild-type p53, with IC50 values of 0.40-4.23 μM, 0.37-1.88 μM and 2.72-9.83 μM for Compound A, Compound B, and Nutlin-3, respectively. These effects were markedly abrogated by siRNA-mediated p53 knockdown and in a cell line harboring a de novo p53 mutation. Compound A and Compound B also induced cell cycle arrest and apoptosis at approximately 5 fold lower concentrations than Nutlin-3. At low concentrations, G0/G1 cell arrest occurred, whereas higher concentrations resulted in G2/M arrest and induction of apoptosis. Cell line and tumor xenograft experiments are ongoing. These data demonstrate that Compounds A and B are highly potent and specific inhibitors of MDM2 with activity in genetically characterized liposarcoma cells. Further study and clinical development in this disease is warranted. 1. Wang S. et al., AACR, Orlando FL, 2011, Abstract LB-204 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2786. doi:1538-7445.AM2012-2786
Helicobacter pylori induces human dendritic cell maturation and duodenal ulcer promoting gene a (dupA) enhances dendritic cell cytokine expression
Authors: M. Z. Cader, C. Marx, E. Staples, K. Robinson, J. Atherton
Journal: Gut (2011)

<h3>Introduction</h3> <i>Helicobacter pylori</i> is the leading cause of peptic ulceration worldwide and possession of duodenal ulcer promoting gene A (<i>dupA</i>) increases ulcer risk. In vitro, <i>dupA</i> increases production of pro-inflammatory cytokines by monocytes, but these cells are not present in gastric mucosal tissue. However, isolation and characterisation of immune cells from human gastric biopsy samples has shown the presence of myeloid dendritic cells. Dendritic cells are antigen-presenting cells with a unique ability to initiate a primary immune response from naïve T-cells. We therefore investigated whether <i>Helicobacter pylori</i> is able to induce dendritic cell maturation and pro-inflammatory cytokine expression and whether this is influenced by the <i>dupA</i> gene. <h3>Methods</h3> Human dendritic cells were derived from circulating monocytes from healthy donors. These cells were co-cultured with <i>H pylori</i> strains AB21 and AB31 and their isogenic <i>dupA</i> knockout mutants. The activation status of dendritic cells was assessed by flow cytometry; cytokine production was quantified by ELISA. <h3>Results</h3> In their resting state the monocyte derived dendritic cells expressed MHC class II, but very low levels of co-stimulatory molecules CD80, CD83 and CD86. Upon culture with <i>H. pylori</i>, the cells expressed significantly higher levels of these co-stimulatory molecules, demonstrating maturation (&gt;25 fold increase in percentage of positive events for CD80, CD83, CD86 on flow cytometry; p&lt;0.01). There were no differences between the responses to wild type and <i>dupA</i> knockout mutant strains, or following stimulation with lipopolysaccharide (LPS). The <i>H. pylori-</i>matured dendritic cells secreted high levels of IL-12p40, IL-12p70, IL-10 and IL-23. The concentrations induced by the <i>dupA</i>+ strains were significantly higher than those induced by the <i>dupA</i> mutants (1.5 fold increase in IL-12p40 production, p&lt;0.05; 1.4 fold increase in IL-12p70, p&lt;0.05). <h3>Conclusion</h3> <i>H pylori</i> induces dendritic cell maturation and secretion of pro-inflammatory cytokines. <i>dupA</i> increases IL-12 production from these dendritic cells. This may explain the enhanced antral gastritis and ulcer risk associated with <i>dupA</i> + <i>H pylori</i> strains.
&lt;emph type="ital"&gt;Mayan Ruins, Yucatan&lt;/emph&gt;
Authors: Janet M. Torpy
Journal: JAMA (2009)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The semi-individual study in air pollution epidemiology: a valid design as compared to ecologic studies.
Authors: N Künzli, I B Tager
Journal: Environmental Health Perspectives (1997)

The assessment of long-term effects of air pollution in humans relies on epidemiologic studies. A widely used design consists of cross-sectional or cohort studies in which ecologic assignment of exposure, based on a fixed-site ambient monitor, is employed. Although health outcome and usually a large number of covariates are measured in individuals, these studies are often called ecological. We will introduce the term semi-individual design for these studies. We review the major properties and limitations with regard to causal inference of truly ecologic studies, in which outcome, exposure, and covariates are available on an aggregate level only. Misclassification problems and issues related to confounding and model specification in truly ecologic studies limit etiologic inference to individuals. In contrast, the semi-individual study shares its methodological and inferential properties with typical individual-level study designs. The major caveat relates to the case where too few study areas, e.g., two or three, are used, which render control of aggregate level confounding impossible. The issue of exposure misclassification is of general concern in epidemiology and not an exclusive problem of the semi-individual design. In a multicenter setting, the semi-individual study is a valuable tool to approach long-term effects of air pollution. Knowledge about the error structure of the ecologically assigned exposure allows consideration of the impact of ecologically assigned exposure on effect estimation. Semi-individual studies, i.e., individual level air pollution studies with ecologic exposure assignment, more readily permit valid inference to individuals and should not be labeled as ecologic studies.
Abstract 3253: Id4 and FKBP52 interaction regulates androgen receptor activity in normal prostate and prostate cancer
Authors: Jugal B. Joshi
Journal: Cancer Research (2014)

Abstract The androgen receptor (AR) is a ligand activated transcription factor and important member of the steroid hormone nuclear receptors. Androgen signaling through AR plays a critical role in prostate tumorigenesis. AR transcriptional enhancement normally requires FKBP52 mediated peptidyl-prolyl cis-trans isomerase (PPIase) activity as well as HSP90-binding ability. FK506 binding protein 4 (FKBP52) is an AR folding factor that has critically important physiological roles in male reproductive tissues. Despite several experimental evidences, the molecular mechanism by which FKBP52 promotes AR signaling in prostate cancer still remains to be investigated. Our previous lab studies have demonstrated that Id4 is regulated by androgens in normal prostate epithelial and LNCaP cells. However, the interaction of Id4 and with the androgen receptor pathway in regulating the development and function of the normal prostate still remains elusive. Here we demonstrate that Id4 (inhibitor of differentiation-4) a dominant negative regulator of bHLH transcription factors can physically interact with AR, FKBP52 and HSP90 in early stage prostate cancer LNCaP cells and thereby selectively regulating AR transcriptional activity. Id4 is highly expressed in the normal prostate and decreased in prostate cancer due to promoter hypermethylation. Loss of Id4 in LNCaP cells resulted in ligand independent AR activation characterized by increased AR nuclear translocation and expression of PSA, FKBP51, FKBP52 and ARD1, the transcriptional targets of AR. Differential protein expression between LNCaP and LNCaP-Id4 demonstrated that loss of Id4 cells significantly elevated the levels of FBKP52 and Hsp27, the two known transcriptional regulators and nuclear transporters of AR. More importantly, LNCaP-Id4 cells were able to synthesize significantly higher levels of testosterone as compared to the androgen-dependent LNCaP cells. In conclusion, we demonstrate that loss of Id4 in LNCaP cells elevates FKBP52 levels, transcriptionally potentiates AR activity which in turn then leads to progression of androgen-independent prostate cancer. NIH grant #R01CA128914 Citation Format: Jugal B. Joshi. Id4 and FKBP52 interaction regulates androgen receptor activity in normal prostate and prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3253. doi:10.1158/1538-7445.AM2014-3253
Decision of the Appellate Court in the Case of Edward C. Sims vs. Andrew H. Parker, M.D.
Authors: Thomas G. McElligott
Journal: JAMA (1891)

Edward C. Sims, Appellant, vs. Andrew H. Parker, Appellee. Appeal from the Circuit Court of Cook County. Moran, P. J. This action was brought to recover damages for an injury alleged by appellant to have been caused to him by a truss improperly applied and adjusted to him by appellee for the cure of hernia, when in fact, he had no hernia. At the close of the evidence at the trial, the Court directed the jury to find a verdict for the defendant. Plaintiff had for some years worn a truss on one side, and in March, 1888, feeling certain pains, he went to defendant's place of business, and told his symptoms, and afterwards was examined by defendant, who told him that he was ruptured. Thereupon plaintiff purchased a truss from defendant, and had him adjust it to his person. After the truss was put on plaintiff suffered great pain,
Bronchial Artery Embolization for the Treatment of Hemoptysis in Patients with Cystic Fibrosis
Authors: GEORGE M. BRINSON, PEADAR G. NOONE, MATTHEW A. MAURO, MICHAEL R. KNOWLES, JAMES R. YANKASKAS, JEET S. SANDHU, PAUL F. JAQUES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Hemoptysis is common in patients with cystic fibrosis (CF). Bleeding may vary in severity, ranging from minor blood-streaking of sputum to expectoration of significant quantities of blood. Major hemoptysis, defined as bleeding greater than 240 ml/24 h, represents a medical emergency. Bronchial artery embolization (BAE) is one of the treatment options for hemoptysis. We reviewed the 10-yr experience at the University of North Carolina Hospitals in the treatment of hemoptysis by BAE. Eighteen patients with CF were hospitalized on 29 occasions and underwent 36 BAE procedures for the control of hemoptysis. Most patients (n = 11) had very severe lung disease (FEV1 < 35%) with a high incidence (n = 9, 50%) of multi-drug-resistant bacteria. Fifteen patients (n = 33 procedures) were followed for a mean of ∼ 22 mo after BAE. The overall efficacy of BAE for initial control of hemoptysis was 75% (n = 22) after one session, 89% (n = 26) after two sessions, and 93% (n = 27) after three sessions. The overall recurrence rate per episode was 46% (12/26 presentations in four patients) with a mean time for recurrence of ∼ 12 mo. There was a high incidence (75%) of bleeding from nonbronchial systemic collateral vessels among patients (n = 7) who had undergone a previous BAE. There were two deaths associated with massive hemoptysis despite BAE. Three patients had transient neurologic deficits during BAE. We concluded that BAE is a relatively safe and effective means of treating significant hemoptysis in patients with CF.
THE PLASMA “AMMONIA” AND GLUTAMINE CONTENT IN PATIENTS WITH HEPATIC COMA 1
Authors: J. Edwin Seegmiller, Robert Schwartz, Charles S. Davidson
Journal: Journal of Clinical Investigation (1954)

Although the clinical state of hepatic coma is well recognized, it has not been associated with any consistent organic lesion of the central nervous system. This has led to the postulation of a biochemical defect to account for the impairment of the central nervous system observed in hepatic coma; however the biochemical nature and the ulti
Effect of a Perioperative, Cardiac Output–Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery
Authors: Rupert M. Pearse, David A. Harrison, Neil MacDonald, Michael A. Gillies, Mark Blunt, Gareth Ackland, Michael P. W. Grocott, Aoife Ahern, Kathryn Griggs, Rachael Scott, Charles Hinds, Kathryn Rowan
Journal: JAMA (2014)

Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.
The effect of diazepam on human gastric secretion
Authors: D. Birnbaum, F. Karmeli, M. Tefera
Journal: Gut (1971)

Human basal gastric secretion is markedly reduced after oral administration of 10 mg diazepam. This effect lasts for five hours.Gastric nocturnal secretion, collected five hours after the last meal, reveals a decline towards the morning hours with an average of 25% in placebo-treated patients. A comparison between placebo and diazepam reveals a significantly greater decrease of 47% in volume after giving parenterally 10 mg diazepam without noticeable side effects.
Green phlegm doesn't always warrant antibiotics, public is told
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Public Health England has issued guidance to the public on when green phlegm needs to be treated with antibiotics.

Research by the organisation’s primary care unit has found that 40% of people believe that antibiotics speed up recovery from a cough with green phlegm and that only 6% believe that antibiotics are beneficial when the phlegm is clear.1

Advice from the unit and the Royal College of General Practitioners says that in otherwise healthy people who don’t smoke and who have no underlying health problems an acute cough with phlegm of any colour is not necessarily a sign of infection and that any small possible benefit from …
A Small Versatile Centrifuge for Blood Banks and Clinical Laboratories
Authors: Alan Richardson Jones
Journal: New England Journal of Medicine (1954)

IN the performance of blood grouping and cross-matching tests a source of inconvenience, and of possible error, is the operation of transferring the tubes in which the reactions are performed from racks to water bath and thence to the centrifuge. In more than one blood bank it has been observed that the reactions between cells and serums were set up in tubes held in a wooden block. From this block the tubes were moved to a metal rack, which supported them in the 37°C. water bath. After incubation the tubes were transferred to the centrifuge, and after centrifugation they were . . .
Providing clean water: lessons from Bangladesh
Authors: R. MacDonald
Journal: BMJ (2001)

The people of Bangladesh are being slowly poisoned. Although the world has known this since 1998, the full implications are only just being realised. Up to 57 million of Bangladesh's 130 million inhabitants are drinking water that contains harmful concentrations of arsenic.1 The tragedy is twofold: it was a well intentioned public health measure that caused the problem in the first place, and there are no easy solutions. Discussion at a meeting in January between the Department for International Development, the British Geological Survey, and non-governmental organisations emphasised the difficulties of reaching a workable long term solution.

The World Health Organization's provisional guideline is that drinking water should contain no more than 10 μg/l of arsenic,2 though the Bangladesh standard is 50 μg/l. Water samples from many Bangladeshi tubewells have concentrations exceeding these values, with extreme concentrations greater than 500 μg/l. 1 3

Chronic arsenic ingestion has many health consequences, ranging from skin disorders to cancer, diabetes, and cardiovascular, respiratory, and peripheral vascular …
A COMPARISON OF THE LONG-TERM SURVIVAL OF 306,868 PATIENTS WITH MULTIVESSEL CORONARY ARTERY DISEASE UNDERGOING CABG AND PCI: A META-ANALYSIS OF RETROSPECTIVE STUDIES
Authors: Stephen W. Davies, Wesley T. O'Neal, Robert G. Sawyer, Jimmy T. Efird, T. Ferguson
Journal: Journal of the American College of Cardiology (2013)
DYSLIPIDEMIC THERAPY AND PLATELET REACTIVITY IN OPTIMALLY TREATED STABLE ISCHEMIC HEART DISEASE PATIENTS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION
Authors: Evgenia Granina, Santosh Padala, Ashraf Seedhom, Mandeep Sidhu, Mikhail Torosoff, William Boden
Journal: Journal of the American College of Cardiology (2014)
Local Dystrophin Restoration with Antisense Oligonucleotide PRO051
Authors: Judith C. van Deutekom, Anneke A. Janson, Ieke B. Ginjaar, Wendy S. Frankhuizen, Annemieke Aartsma-Rus, Mattie Bremmer-Bout, Johan T. den Dunnen, Klaas Koop, Anneke J. van der Kooi, Nathalie M. Goemans, Sjef J. de Kimpe, Peter F. Ekhart, Edna H. Venneker, Gerard J. Platenburg, Jan J. Verschuuren, Gert-Jan B. van Ommen
Journal: New England Journal of Medicine (2007)

Duchenne's muscular dystrophy is associated with severe, progressive muscle weakness and typically leads to death between the ages of 20 and 35 years. By inducing specific exon skipping during messenger RNA (mRNA) splicing, antisense compounds were recently shown to correct the open reading frame of the DMD gene and thus to restore dystrophin expression in vitro and in animal models in vivo. We explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease.Four patients, who were selected on the basis of their mutational status, muscle condition, and positive exon-skipping response to PRO051 in vitro, received a dose of 0.8 mg of PRO051 injected into the tibialis anterior muscle. A biopsy was performed 28 days later. Safety measures, composition of mRNA, and dystrophin expression were assessed.PRO051 injection was not associated with clinically apparent adverse events. Each patient showed specific skipping of exon 51 and sarcolemmal dystrophin in 64 to 97% of myofibers. The amount of dystrophin in total protein extracts ranged from 3 to 12% of that found in the control specimen and from 17 to 35% of that of the control specimen in the quantitative ratio of dystrophin to laminin alpha2.Intramuscular injection of antisense oligonucleotide PRO051 induced dystrophin synthesis in four patients with Duchenne's muscular dystrophy who had suitable mutations, suggesting that further studies might be feasible.
Corrigendum to: “Prevalence of Hypospadias in Danish Boys: A Longitudinal Study, 1977–2005” [Eur Urol 2009;55:1022–26]
Authors: Lars Lund, Malene C. Engebjerg, Lars Pedersen, Vera Ehrenstein, Mette Nørgaard, Henrik Toft Sørensen
Journal: European Urology (2009)