tbuckley/cabot-search huggingface dataset:
Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages.
Authors: S J Lolait, J A Clements, A J Markwick, C Cheng, M McNally, A I Smith, J W Funder
Journal: Journal of Clinical Investigation (1986)

We have previously demonstrated low levels of immunoreactive (ir)-beta-endorphin (beta-EP) and ir-ACTH in a subpopulation of mouse spleen macrophages, which is consistent with an involvement of opioid peptides in modulation of immune responses. Gel chromatography studies suggested the presence of an approximately 3.5,000-molecular weight (mol wt) species, putatively beta-EP, an approximately 11.5,000-mol-wt species, putatively beta-lipotropin, and a higher molecular weight species (putative beta-EP precursor, pro-opiomelanocortin (POMC). In this study we have extended our original findings by demonstrating the presence of messenger RNA for POMC by the use of a complementary DNA probe and Northern blot analysis of extracts of mouse and rat spleen. In addition, using high performance liquid chromatography (HPLC), we have shown that the major endorphin species in mouse spleen macrophages is beta-EP1-31, and that there are smaller amounts of each of the acetylated forms, N-acetyl-beta-EP1-16 (alpha-endorphin), N-acetyl-beta-EP1-17 (gamma-endorphin), N-acetyl-beta-EP1-27, and N-acetyl-beta-EP1-31. We interpret these studies as showing that (a) the spleen is an organ of POMC synthesis and that (b) the predominant COOH-terminal product of macrophage POMC is the opiate-receptor active species beta-EP1-31.
Disease progression into adulthood and predictors of long-term active disease in juvenile idiopathic arthritis
Authors: Anne M Selvaag, Hanne A Aulie, Vibke Lilleby, Berit Flatø
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To describe disease activity 30 years after disease onset in a previously studied cohort of patients with juvenile idiopathic arthritis (JIA) and reveal predictors of long-term active disease. <h3>Methods</h3> Patients with JIA, first referred 1980–1985 and re-examined 15 and 23 years after onset, were invited to attend. All 176 patients were assessed by questionnaires. Patients with signs of active disease at 15 years or later also came to a clinical re-examination (n=90). Disease activity was assessed by the clinical juvenile arthritis disease activity score (JADAS3) and by the criteria for remission in JIA, and health status by Health Assessment Questionnaire (HAQ) and Medical Outcome Study 36-item Short Form Health Survey (SF-36). <h3>Results</h3> At 30-year follow-up, 59% of the patients were in clinical remission off medication, 7% were in remission on medication and 34% had active disease. 70% of the patients were in the same category of disease activity at 15 and 30 years. The JADAS3 was ≤2.0 in 54%, 2.1–4.5 in 18% and &gt;4.5 in 28%. HLA-DRB1*01, physician9s global assessment and a short total time in remission at 15 years, predicted active disease. Physician9s global assessment also predicted a JADAS3 &gt;4.5. From 15 to 30 years (n=90), physician9s global assessment, number of active joints, erythrocyte sedimentation rate and C reactive protein improved significantly, but patient9s global assessment, HAQ and SF-36 did not. <h3>Conclusions</h3> 41% of the patients with JIA had active disease or were on medication after 30 years and 28% had a high symptom state. Remission rates and patient-reported health status at 15 years were comparable with rates at 30 years.
Social inequalities in non-small cell lung cancer management and survival: a population-based study in central Sweden
Authors: A. Berglund, L. Holmberg, C. Tishelman, G. Wagenius, S. Eaker, M. Lambe
Journal: Thorax (2010)

<h3>Objectives</h3> To examine possible associations between socioeconomic status, management and survival of patients with non-small cell lung cancer (NSCLC). <h3>Methods</h3> In a population-based cohort study, information was retrieved from the Regional Lung Cancer Register in central Sweden, the Cause of Death Register and a social database. ORs and HRs were compared to assess associations between educational level and management and survival. <h3>Results</h3> 3370 eligible patients with an NSCLC diagnosis between 1996 and 2004 were identified. There were no differences in stage at diagnosis between educational groups. A higher diagnostic intensity was observed in patients with high compared with low education. There were also social gradients in time between referral and diagnosis in early stage disease (median time: low, 32 days; high, 17 days). Social differences in treatment remained following adjustment for prognostic factors (surgery in early stage disease, high vs low OR 2.84; CI 1.40 to 5.79). Following adjustment for prognostic factors and treatment, the risk of death in early stage disease was lower in women with a high education (high vs low HR 0.33; CI 0.14 to 0.77). <h3>Conclusion</h3> The results of this study indicate that socioeconomically disadvantaged groups with NSCLC receive less intensive care. Low education remained an independent predictor of poor survival only in women with early stage disease. The exact underlying mechanisms of these social inequalities are unknown, but differences in access to care, co-morbidity and lifestyle factors may all contribute.
Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer
Authors: P. Dhawan
Journal: Journal of Clinical Investigation (2005)

Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer cell invasion and metastasis. The role of adherent junction proteins has been studied extensively in cancer, but the roles of tight junction (TJ) proteins are less well understood. Claudins are recently identified members of the tetraspanin family of proteins, which are integral to the structure and function of TJs. Recent studies show changes in expression/cellular localization of claudins during tumorigenesis; however, a causal relationship between claudin expression/localization and cancer has not been established. Here, we report an increased expression of claudin-1 in human primary colon carcinoma and metastasis and in cell lines derived from primary and metastatic tumors. We also report frequent nuclear localization of claudin-1 in these samples. Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition. Furthermore, we demonstrate that changes in claudin-1 expression have significant effects on growth of xenografted tumors and metastasis in athymic mice. We further provide data suggesting that the regulation of E-cadherin expression and beta-catenin/Tcf signaling is a possible mechanism underlying claudin-1-dependent changes.
Pholcodine exposure raises serum IgE in patients with previous anaphylaxis to neuromuscular blocking agents
Authors: T. Harboe, S. G. O. Johansson, E. Florvaag, H. Öman
Journal: Allergy (2007)

Background: Neuromuscular blocking agents (NMBAs) can cause anaphylaxis through immunoglobulin E (IgE) antibodies that bind quaternary ammonium ion epitopes. These epitopes are present in numerous common chemicals and drugs, exposure to which, theoretically, could be of importance in the development and maintenance of the IgE sensitization promoting allergic reactions. Pholcodine is one such drug, which in a recent pilot study was shown to induce a remarkable increase in serum IgE levels in two IgE‐sensitized individuals. The present study explores the effect of pholcodine exposure on IgE in a population with previously diagnosed IgE‐mediated anaphylaxis towards NMBAs. Methods: Seventeen patients were randomized to 1 week’s exposure with cough syrup containing either pholcodine or guaifenesin. The primary variables serum IgE and IgE antibodies towards pholcodine, morphine and suxamethonium were measured before and 4 and 8 weeks after start of exposure. Results: Patients exposed to pholcodine had a sharp rise in levels of IgE antibodies towards pholcodine, morphine and suxamethonium, the median proportional increases 4 weeks after exposure reaching 39.0, 38.6 and 93.0 times that of the base levels respectively. Median proportional increase of IgE was 19.0. No changes were observed in the guaifenesin group. Conclusion: Serum levels of IgE antibodies associated with allergy towards NMBAs increase significantly in sensitized patients after exposure to cough syrup containing pholcodine. Availability of pholcodine should be restricted by medical authorities because of the potential risk of future allergic reactions to muscle relaxants.
Role of Persistent, Non-Genotoxic Tissue Damage in Rodent Cancer and Relevance to Humans
Authors: P Grasso, M Sharratt, A J Cohen
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
A pilot trial of mobile, patient-performed teledermoscopy
Authors: M.N. Manahan, H.P. Soyer, L.J. Loescher, C. Horsham, D. Vagenas, D.C. Whiteman, C.M. Olsen, M. Janda
Journal: British Journal of Dermatology (2014)

Early detection by skin self-examination (SSE) could improve outcomes for melanoma. Mobile teledermoscopy may aid this process.To establish the clinical accuracy of SSE plus mobile teledermoscopy vs. clinical skin examination (CSE) and to test whether providing people with detailed SSE instructions improves accuracy.Men and women aged 50-64 years (n = 58) performed SSE plus mobile teledermoscopy in their homes between May and November 2013 and were given technical instructions plus detailed SSE instructions (intervention) or technical instructions only (control). Within 3 months, they underwent a CSE. Outcome measures included (i) body sites examined, lesions photographed, and missed; (ii) sensitivity of SSE plus mobile teledermoscopy vs. in-person CSE using either patients or lesions as denominator; and (iii) concordance of telediagnosis with CSE.Overall 49 of 58 randomized participants completed the study, and submitted 309 lesions to the teledermatologist. Intervention-group participants were more likely to submit lesions from their legs compared with controls (P = 0·03), with no other differences. Eleven participants (22%) did not photograph 14 pigmented lesions that the dermatologist considered worthwhile photographing or monitoring. The sensitivity of SSE plus mobile teledermoscopy was 82% using the patient as denominator and 42% using the lesion as denominator. There was substantial agreement between telediagnosis and CSE (κ = 0·90), accounting for differential diagnoses.SSE plus mobile teledermoscopy is promising for surveillance of particular lesions even without detailed SSE instructions. However, in the format tested in this study, consumers may overlook lesions and send many nonpigmented lesions. This investigation demonstrates that high-quality dermoscopic images can be taken by patients at home with high accuracy.
Interstitial pulmonary disorders in indium-processing workers
Authors: T. Chonan, O. Taguchi, K. Omae
Journal: European Respiratory Journal (2006)

The production of indium-tin oxide has increased, owing to the increased manufacture of liquid-crystal panels. It has been reported that interstitial pneumonia occurred in two indium-processing workers; therefore, the present study aimed to evaluate whether interstitial pulmonary disorders were prevalent among indium workers. The study was carried out in 108 male workers in the indium plant where the two interstitial pneumonia patients mentioned above were employed, and included high-resolution computed tomography (HRCT) of the lungs, pulmonary function tests and analysis of serum sialylated carbohydrate antigen KL-6 and the serum indium concentration. Significant interstitial changes were observed in 23 indium workers on HRCT and serum KL-6 was abnormally high (&gt;500 U·mL -1 ) in 40 workers. Workers with serum indium concentrations in the highest quartile had significantly longer exposure periods, greater HRCT changes, lower diffusing capacity of the lung for carbon monoxide and higher KL-6 levels compared with those in the lowest quartile. The serum indium concentration was positively correlated with the KL-6 level and with the degree of HRCT changes. In conclusion, the results of the present study indicated that serum KL-6 and high-resolution computed tomography abnormalities were prevalent among indium workers and that these abnormalities increased with the indium burden, suggesting that inhaled indium could be a potential cause of occupational lung disease.
In vitro and in vivo myelotoxicity of CAI to human and murine hematopoietic progenitor cells
Authors: Donna A. Volpe, Kristina Cole, Mary Ann Sandeen, Elise C. Kohn
Journal: American Journal of Hematology (1995)

Carboxyamido-triazole (CAI), an agent that targets calcium-sensitive signal transduction pathways, has both antiproliferative and antimetastatic properties. The objective of this study was to evaluate the myelotoxicity of CAI to normal human and murine hematopoietic cells. In vitro toxicity of CAI was determined by inhibition of myeloid [colony-forming unit-granulocyte/macrophage (CFU-gm)] and erythroid [burst-forming unit-erythroid (BFU-e)] colony formation in clonal assays. The effects of oral CAI on CD2F1 mouse marrow and splenic cellularity, marrow progenitor content, and peripheral blood cell counts were assessed in relation to plasma CAI levels. In vitro, CAI caused a concentration-dependent inhibition of CFU-gm and BFU-e colonies following continuous drug exposure. Murine CFU-gm and BFU-e were inhibited > 90% by 10 and 15 micrograms/mL CAI, respectively. However, suppression of human CFU-gm and BFU-e did not exceed 65% at the same concentrations. In vivo, CAI reduced the number of CFU-gm and BFU-e per femur after the initial dose and through day 4. Variations in colony inhibition paralleled changes in CAI plasma concentrations. While colony inhibition increased in vitro with escalating drug concentrations, this was not observed in vivo with additional CAI doses. The low toxicity of CAI in vivo combined with the significant difference between toxicity for human and mouse progenitors in vitro suggests a relatively low adverse potential to the bone marrow for this new signal transduction inhibitory agent.
Transmission of Pneumocystis carinii from patients to hospital staff
Authors: B. Lundgren, K. Elvin, L. P. Rothman, I. Ljungstrom, C. Lidman, J. D. Lundgren
Journal: Thorax (1997)

BACKGROUND: An extrahuman reservoir of human pathogenic Pneumocystis carinii remains unknown. Host to host transmission has been described in animal studies and in cluster cases among immunodeficient patients. P carinii DNA has recently been detected in air filters from inpatient and outpatient rooms in departments of infectious diseases managing patients with P carinii pneumonia (PCP), suggesting the airborne route of transmission. Exposure of staff to P carinii may occur in hospital departments treating patients with PCP. METHODS: Exposure to P carinii was detected by serological responses to human P carinii by ELISA, Western blotting, and indirect immunofluorescence in 64 hospital staff with and 79 staff without exposure to patients with PCP from Denmark and Sweden. DNA amplification of oropharyngeal washings was performed on 20 Danish staff with and 20 staff without exposure to patients with PCP. RESULTS: There was no significant difference in the frequency or level of antibodies to P carinii between staff exposed and those unexposed to patients with PCP. None of the hospital staff had detectable P carinii DNA in oropharyngeal washings. CONCLUSIONS: There is no difference in antibodies and no detectable P carinii DNA in oropharyngeal washings, which suggests that immunocompetent staff treating patients with PCP are not a potentially infectious source of P carinii for immunocompromised patients.
Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex
Authors: A.G. Logan, R. Tkacova, S.M. Perlikowski, R.S. Leung, A. Tisler, J.S. Floras, T.D. Bradley
Journal: European Respiratory Journal (2003)

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night9s application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3±6.8 to 126.0±6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7±4.5 to 72.9±4.5). CPAP usage for 2 months was accompanied by an 11.0±4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4±4.4 and 9.3±3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8±3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.
Involvement of casein kinase Iϵ in cytokine-induced granulocytic differentiation
Authors: Atsuo Okamura, Nobuko Iwata, Aki Nagata, Akira Tamekane, Manabu Shimoyama, Hiroshi Gomyo, Kimikazu Yakushijin, Norinaga Urahama, Miyuki Hamaguchi, Chie Fukui, Kazuo Chihara, Mitsuhiro Ito, Toshimitsu Matsui
Journal: Blood (2004)
Duration of QRS Complex in Resting Electrocardiogram Is a Predictor of Sudden Cardiac Death in Men
Authors: Sudhir Kurl, Timo H. Mäkikallio, Pentti Rautaharju, Vesa Kiviniemi, Jari A. Laukkanen
Journal: Circulation (2012)

Previous studies indicate that increased QRS duration in ECG is related to the risk of all-cause death. However, the association of QRS duration with the risk of sudden cardiac death (SCD) is not well documented in large population-based studies. Our aim was to examine the relation of QRS duration with SCD in a population-based sample of men.This prospective study was based on a cohort of 2049 men aged 42 to 60 years at baseline with a 19-year follow-up, during which a total of 156 SCDs occurred. As a continuous variable, each 10-ms increase in QRS duration was associated with a 27% higher risk for SCD (relative risk, 1.27; 95% confidence interval, 1.14-1.40; P<0.001). Subjects with QRS duration of >110 ms (highest quintile) had a 2.50-fold risk for SCD (relative risk, 2.50; 95% confidence interval, 1.38-4.55; P=0.002) compared with those with QRS duration of <96 ms (lowest quintile), after adjustment for established key demographic and clinical risk factors (age, alcohol consumption, previous myocardial infarction, smoking, serum low- and high-density lipoprotein cholesterol, C-reactive protein, type 2 diabetes mellitus, body mass index, systolic blood pressure, and cardiorespiratory fitness). In addition to QRS duration, smoking, previous myocardial infarction, type 2 diabetes mellitus, cardiorespiratory fitness, body mass index, systolic blood pressure, and C-reactive protein were independently associated with the risk of SCD.QRS duration is an independent predictor of the risk of SCD and may have utility in estimating SCD risk in the general population.
On Perchloride of Mercury in the Diarrh a of Typhoid Fever
Authors: T. L. Walford
Journal: BMJ (1874)

came; and, at I I A. M., I got him to perform.He put a basin which I brought himii on the floor, inclined his body forward, and discharged easily, at one large mouthful, about three and a half ounces of healthy pure pus.He never has had a rigor or chill, or ague, nor sweats.XVhence can this pus come, with such regularity every day for four years, the patienit being without cough, or vomit, or wasting, but in the best of health?Can it be abscess in the oesopha-eal tube ?It is assuredly not in the bronchial tube, or any of its appendages, above or below.
Promise and Peril of e-Cigarettes
Authors: David B. Abrams
Journal: JAMA (2014)

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
CSN5 Isopeptidase Activity Links COP9 Signalosome Activation to Breast Cancer Progression
Authors: Adam S. Adler, Laurie E. Littlepage, Meihong Lin, Tiara L.A. Kawahara, David J. Wong, Zena Werb, Howard Y. Chang
Journal: Cancer Research (2008)

Abstract CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here, we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. [Cancer Res 2008;68(2):506–15]