tbuckley/cabot-search huggingface dataset:
Enhancing Effect of Excess Topical Vitamin A on Rous Sarcomas in Chickens<xref ref-type="fn" rid="FN2">2</xref>
Authors: Aaron Polliack, M.D., Zalman Ben Sasson, M.Sc.
Journal: JNCI Journal of the National Cancer Institute (1972)

The right and left wing webs of 36 White Leghorn chickens were inoculated with varying amounts of Rous sarcoma virus (RSV), ranging from 5000–100,000 focus-forming units (FFU) per injection. Thereafter, the right wing webs were painted daily with topical 20% vitamin A palmitate in paraffin oil for 3 weeks. The contralateral wing web was left untreated for a similar period, and 22.2% of the birds developed fibrosarcomas measuring 1–2 cm in diameter and weighing from 6–30 g. On the side treated with vitamin A, 52.8% of the webs had large tumors weighing up to 240 g and measuring from 6–13 cm in diameter. Tumors developed in 50% of the webs given smaller doses of RSV (5000–20,000 FFU) followed by topical vitamin A, as opposed to 15% in webs given similar small doses of RSV alone. The tumors developing after topical vitamin A were more aggressive both macroscopicaily and histologically. They infiltrated muscle and bone and even metastasized. They also had large amounts of muco-polysaccharides in the stroma. When the wings of 10 chickens were treated with topical vitamin A palmitate before injection of RSV, tumors weighing from 6–20 g developed in all treated webs, whereas tumors weighing from 1–5 g developed in 6 of the 10 wing webs not treated with vitamin A. The results are attributed to the established membrane-labilizing qualities of the vitamin which probably enhance tumorigenesis, either by facilitating more effective entry of the virus into the tissues or by altering the structure and function of the virus and target cell in a manner more amenable to malignant transformation.
Hypercalcaemia in Cleveland: A Hospital-Based Survey
Authors: A Rajathurai, R Cove-Smith
Journal: Journal of the Royal Society of Medicine (1984)

Over a period of six months all reports in the South Tees Health District of serum calcium levels greater than 2.70 mmol/1 were extracted and patient records examined to establish the associated diseases and patterns of management. A total of 235 reports were evaluated, and after exclusion of doubtful cases 196 patients were included in the study. No cause had been identified in 57 (29%). Many of these were elderly females in whom hypercalcaemia may have been due to primary hyperparathyroidism, but parathyroid hormone levels had not been measured. Of those in whom a diagnosis had been made, 62 (45%) were associated with malignancy and 50 (36%) with chronic renal failure. 72% of cases of hypercalcaemia reported to general practitioners and 13% of those reported to hospital doctors were not investigated further. Despite the inclusion of serum calcium estimation on routine biochemical profiles, many cases of hypercalcaemia are being ignored or not investigated further. The study emphasizes the need for a reliable screening test for primary hyperparathyroidism.
Adult thoracic empyema: A comparative analysis of tuberculous and nontuberculous etiology in 75 patients
Authors: Somenath Kundu, Subhra Mitra, Subhasis Mukherjee, Soumya Das
Journal: European Respiratory Journal (2011)

Background:  Thoracic empyema is a disease of significant morbidity and mortality in the developing world where tuberculosis is a common cause. Clinical outcomes in tuberculous empyema are complicated by fibrocavitary disease and bronchopleural fistulae. A prospective study to compare the clinical profiles and outcomes of patients with tuberculous and nontuberculous empyema was performed.   Materials and methods:  A prospective study of adult nonsurgical thoracic empyema cases admitted in a teaching hospital in India was performed over a period of 18 months. A comparative analysis of clinical characteristics, treatment modalities, and outcomes of patients with tuberculous and nontuberculous empyema was carried out.   Results:  75 cases of empyema were seen during the study period, of which 46 (61.3%) were of nontuberculous etiology while tuberculosis constituted 29 (38.7%) cases. Among the nontuberculous empyema patients, Staphylococcus aureus (11, 23.93%) was the most frequent pathogen isolated. Tuberculous empyema was more frequent in younger population compared to nontuberculous empyema (mean age of 32.7 years vs. 46.5 years). Duration of illness and mean duration of chest tube drainage were longer (48.7 vs. 23.2 days) in patients with tuberculous empyema. Also the presence of parenchymal lesions and bronchopleural fistula often requiring surgical drainage procedures was more in tuberculous empyema patients.   Conclusion:  Tuberculous is a common cause of empyema thoracis in a developing country. Tuberculous empyema differs from nontuberculous empyema in the age profile, clinical presentation, management issues, and has a significantly poorer outcome.
Respiratory and peripheral muscle strength, functional capacity, dyspnea and physical activity levels in patients with COPD and heart failure
Authors: Meral Bosnak-Guclu, Sema Savci, Deniz Inal-Ince, Hulya Arikan, Erol Tülümen, Melda Saglam, Naciye Vardar-Yagli, Nurdan Kokturk, Kudret Aytemir, Lütfi Cöplü, Lale Tokgözoglu
Journal: European Respiratory Journal (2011)

Aim:  To compare lung function, respiratory and peripheral muscle strength, functional capacity, dyspnea and physical activity levels between patients with COPD and heart failure and find out the best determinant factors of functional capacity.   Methods:  Thirty patients in each group; COPD (64.30±6.37 years, FEV 1 =52.86±11.92, GOLD II/III=20/10) and heart failure (67.73±9.28 years, EF=34.68±7.41, NYHA II/III=20/10) were included. Pulmonary function was evaluated using spirometry, respiratory muscle strength (MIP and MEP) using a mouth pressure device, quadriceps femoris (QF) muscle strength using a hand held dynamometer, functional capacity using six-minute walk test (6MWT), dyspnea using Modified Medical Research Council Dyspnea Scale, energy expenditure during physical activities using International Physical Activity Questionnaire.   Results:  Pulmonary function, QF muscle strength and MMRC scores were significantly lower; MIP, 6MWT distance and energy expenditure in activities were higher in patients with COPD compared to heart failure (p 2 =0.17, p=0.039) and QF muscle strength (R 2 =0.28, p=0.024) in COPD;%75 of the variance was explained by QF muscle strength (p   Conclusion:  COPD patients are more active in daily living and have better functional capacity and respiratory muscle strength with less dyspnea perception. Pulmonary function and peripheral muscle strength are more impaired in patients with COPD compared to heart failure. Muscle strength best predict functional capacity in COPD and heart failure.
Impact of cigarette smoke exposure on Pseudomonas clearance in serpinB1-/- mice
Authors: Tiziana Patrizia Cremona, Charaf Benarafa
Journal: European Respiratory Journal (2012)

Opportunistic pathogens colonize the lungs of COPD patients and contribute to exacerbations. Cigarette smoke exposure induces pulmonary inflammation and is associated with increased incidence and morbidity of pulmonary infections but specific mechanisms linking smoke exposure to defective microbial clearance remain to be defined. Knock-out mice for serpinB1 (sB1-/-), a potent inhibitor of neutrophil proteases, have a severe defect in Pseudomonas clearance associated with increased inflammation, neutrophil death and proteolysis of antimicrobial molecules. In this study, we investigated the combined effects of cigarette smoke exposure and excess neutrophil proteases on Pseudomonas clearance. sB1-/- and wild-type mice were exposed to cigarette smoke or room air (control) for 6 weeks and infected intranasally 24h later. As shown previously, control sB1-/- mice had a severe defect in bacterial clearance compared to control wild-type mice 20h post infection. Surprisingly, clearance was dramatically improved in smoke-exposed sB1-/- mice, which had very low bacterial counts similar to smoke-exposed and control wild-type mice. At earlier time points (4 & 9h post infection), smoke-exposed wild-type mice also had lower bacterial counts than control wild-type mice. All groups of mice had similar bacterial counts 30min after infection suggesting no effect of prior smoke exposure on initial Pseudomonas survival. No increase in Pseudomonas-specific serum antibodies or neutrophil numbers was seen in smoke-exposed compared to their respective control mice. Our findings indicate that protease:inhibitor imbalance and acute cigarette smoke exposure differentially affect the kinetics of Pseudomonas clearance in the lung.
Pathogenesis of Virus-Induced Murine Sarcoma. I. Light Microscopy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Richard Siegler
Journal: JNCI Journal of the National Cancer Institute (1970)

The pathogenesis of the lesion induced by Harvey and Moloney isolates of the murine sarcoma virus was studied to determine its mode of evolution. After inoculation, the lesion was found to begin with an early inflammatory response and to evolve through a granulomatous phase. Then mesenchymal cells proliferated extensively, creating a large mass. The histologic characteristics of this proliferative phase were judged to be those of a sarcoma. Under the experimental conditions, these lesions thereafter regressed. From the manner of tumor evolution, it is suggested that this tumor does not evolve by clonal proliferation, but rather is evoked from continuous recruitment of normal contiguous cells by new viral infection.
Spread of tuberculosis among household contacts of multi drug resistant tuberculosis (MDRTB) patients
Authors: Davis Paul, Sajeevan Kollikkara
Journal: European Respiratory Journal (2014)

Introduction  WHO recommends contact tracing of MDRTB patients to prevent further spread. This study was undertaken in this background to know the proportion of MDRTB among the household contacts of MDRTB patients registered in the national control program (DOTS Plus) in Thrissur Kerala(India)  Objective  To find out the proportion of MDRTB among household contacts of MDRTB patients  Method  This is a cross sectional study among household contacts of MDRTB patients registered under DOTS Plus in Thrissur District from 2010 to 2013 and is compared with an equal number of drug sensitive TB( DSTB). All contacts were examined and those with symptoms or signs were subjected to Chest X-ray and sputum examination. Diagnosis of TB was made either by sputum positivity or by previous treatment for confirmed TB. MDRTB was diagnosed by drug sensitivity tests.  Result  There were 74 MDR TB patients registered in DOTS Plus of which 61( 82.4%) were studied.Number of household contacts of MDRTB were 260 and that of DSTB were 177.Contacts with symptoms in MDRTB group 30.38%(n 79) and DSTB group 35.55(n 63).Contacts with proven TB in MDRTB group 4.61%(n 12; 95% CI 2.1- 7.2%), in DSTB group 6.21% (n 11 95% CI 2.7- 9.8%) p valve 0.536.Number of patients with MDRTB among contacts with MDRTB patients 1.15% (n 3) and that in DSTB patients 0%  Conclusion  The household contacts of MDRTB can develop both drug sensitive as well as drug resistant tuberculosis.There were no resistant TB among household contacts of DSTB  Reference  1)Singla N, Singla R, Jain G, Habib L, Behera DTuberculosis among household contacts of multidrug-resistant tuberculosis patients in Delhi, IndiaInt J Tuberc Lung Dis. 2011 Oct;15(10):1326-30.
Graft-Versus-Tumor Induction With Donor Leukocyte Infusions as Primary Therapy for Patients With Malignancies
Authors: David L. Porter, Jean M. Connors, Vivianna M.D. Van Deerlin, Kathleen M. Duffy, Carol McGarigle, Susan L. Saidman, Debra G.B. Leonard, Joseph H. Antin
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Histocompatible allogeneic donor leukocyte infusions (DLIs) were administered as primary cancer therapy in a phase I trial to determine (1) whether mixed chimerism could be detected without a prior allogeneic transplantation, (2) the toxicity of primary DLI, and (3) whether a graft-versus-tumor (GVT) reaction could be observed. PATIENTS AND METHODS: Eighteen patients were studied. Patients received interferon alfa-2b for a minimum of 4 weeks, followed by DLI (level 1). Patients with no toxicity or engraftment were eligible to receive cytarabine or cyclophosphamide followed by another course of DLI (level 2). Engraftment was determined using polymerase chain reaction amplification of donor and host-specific DNA polymorphisms. RESULTS: Donor cells were detected in the blood in 14 of 16 assessable patients within 1 hour of DLI. Chimerism detectable 4 weeks after DLI was observed in four patients, and five patients were not assessable. Prior autologous transplantation was associated with late chimerism (P = .0014). Acute graft-versus-host disease (GVHD) occurred in four of 16 assessable patients (grade 1, two patients; grade 2, one patient; grade 4, one patient). One patient with grade 4 acute GVHD developed pancytopenia. Only the four patients treated after prior autologous transplantation developed acute GVHD (P = .0005). Three of four patients with acute GVHD and late chimerism responded to primary DLI, and one patient was not assessable for response. CONCLUSION: Allogeneic adoptive immunotherapy resulted in sustained chimerism, acute GVHD, and a GVT response in heavily pretreated patients. This indicates that it may be possible to generate a direct GVT response for patients with malignancies without the need for intensive conditioning therapy immediately before DLI. Immunosuppression may be required for sustained donor cell engraftment.
Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration
Authors: Myra Noemi Chávez, Thilo Ludwig Schenck, Ursula Hopfner, Carolina Centeno-Cerdas, Ian Somlai-Schweiger, Christian Schwarz, Hans-Günther Machens, Mathias Heikenwalder, María Rosa Bono, Miguel L. Allende, Jörg Nickelsen, José Tomás Egaña
Journal: Biomaterials (2015)
Respiratory event hospitalizations are reduced in heart failure patients with comorbid chronic obstructive pulmonary disease using a wireless implanted pulmonary artery pressure monitoring system
Authors: Fernando Martinez, Robert Bourge, Raymond Benza, William Abraham, Philip Adamson, Jay Yadav, Brad Jeffries, Jordan Bauman, Gerard Criner
Journal: European Respiratory Journal (2012)

Introduction: Respiratory event hospitalizations (REH) from COPD exacerbations, bronchitis, pneumonia, and other respiratory events frequently occur in patients with heart failure (HF). Pulmonary artery pressure (PAP) monitoring and treatment has been shown to reduce heart failure hospitalizations.  Objectives: We performed a retrospective analysis to see if PAP monitoring impacts REH in HF patients who had a medical history of COPD and/or were receiving COPD therapies.  Methods: The CHAMPION trial enrolled 550 patients with NYHA class III HF who were followed for an average of 15 months. In all patients PAP data were monitored using a novel, implantable hemodynamic system. In the treatment group, clinicians used PAP data to guide therapy decisions in addition to standard of care versus standard of care alone in the control group.  Results: REH rates were higher in the COPD subgroup compared to the entire CHAMPION cohort. In the COPD subgroup (91 treatment vs. 96 control), treatment experienced a 62% reduction in REH rates (0.12 vs. 0.31, HR 0.38, 95% CI 0.21-0.71, p=0.0023, Anderson-Gill). In the CHAMPION cohort (270 treatment vs. 280 control), treatment experienced a 49% reduction in REH rates (0.07 vs. 0.14, HR 0.51, 95% CI 0.44-0.81, p=0.0009).  Conclusions: Treating HF patients with an implantable hemodynamic monitoring system significantly reduced REH in all patients with even greater benefit in COPD patients. Further investigations that analyze the relationship between PAP, COPD, and REH in chronic HF patients and its implication towards new treatment strategies are warranted.
Phase I study of intravenous menogaril administered intermittently.
Authors: P Dodion, C Sessa, R Joss, N Crespeigne, Y Willems, M Kitt, J Abrams, C Finet, J E Brewer, W J Adams
Journal: Journal of Clinical Oncology (1986)

Thirty-three adult patients with solid tumors were treated with menogaril, a new anthracycline antibiotic. The drug was given as a two-hour infusion every 4 to 5 weeks at doses ranging from 17 to 250 mg/m2. The maximum tolerated dose was 250 mg/m2. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal 2 weeks after treatment, and recovery usually occurred within 4 weeks. There was no dissociation between WBC and neutrophil counts, and myelosuppression did not appear to be cumulative up to 200 mg/m2. Myelosuppression was more severe for patients with heavy pretreatment and/or bone marrow involvement. Local toxicity consisting of phlebitis and/or erythema was the most common nonhematologic toxicity, especially at 250 mg/m2 (eight out of nine patients). Usually, erythema appeared within 24 hours after treatment at or near the infusion site and resolved within a few days. Occasionally, a more persistent (several weeks) orange discoloration suggesting cutaneous deposits of menogaril was observed. Nausea and vomiting were uncommon and never severe. Alopecia and mucositis were rare. Minor arrhythmias were seen in several patients during treatment, but their relationship with menogaril therapy was unclear, and in no patient did heart failure develop. Plasma concentrations were best described by a tricompartmental model with a mean terminal half-life of 29.5 hours and a mean total-body clearance of 20.2 L/h/m2. Doses of 160 and 200 mg/m2 are recommended for phase II trials in poor- and good-risk patients, respectively.
Human Enhancers Are Fragile and Prone to Deactivating Mutations
Authors: Shan Li, Ivan Ovcharenko
Journal: Molecular Biology and Evolution (2015)

To explore the underlying mechanisms whereby noncoding variants affect transcriptional regulation, we identified nucleotides capable of disrupting binding of transcription factors and deactivating enhancers if mutated (dubbed candidate killer mutations or KMs) in HepG2 enhancers. On average, approximately 11% of enhancer positions are prone to KMs. A comparable number of enhancer positions are capable of creating de novo binding sites via a single-nucleotide mutation (dubbed candidate restoration mutations or RSs). Both KM and RS positions are evolutionarily conserved and tend to form clusters within an enhancer. We observed that KMs have the most deleterious effect on enhancer activity. In contrast, RSs have a smaller effect in increasing enhancer activity. Additionally, the KMs are strongly associated with liver-related Genome Wide Association Study traits compared with other HepG2 enhancer regions. By applying our framework to lymphoblastoid cell lines, we found that KMs underlie differential binding of transcription factors and differential local chromatin accessibility. The gene expression quantitative trait loci associated with the tissue-specific genes are strongly enriched in KM positions. In summary, we conclude that the KMs have the greatest impact on the level of gene expression and are likely to be the causal variants of tissue-specific gene expression and disease predisposition.
Differential Role of G Protein–Coupled Receptor Kinase 5 in Physiological Versus Pathological Cardiac Hypertrophy
Authors: Christopher J. Traynham, Alessandro Cannavo, Yan Zhou, Alexandre G. Vouga, Benjamin P. Woodall, Jonathan Hullmann, Jessica Ibetti, Jessica I. Gold, J. Kurt Chuprun, Erhe Gao, Walter J. Koch
Journal: Circulation Research (2015)

G protein-coupled receptor kinases (GRKs) are dynamic regulators of cellular signaling. GRK5 is highly expressed within myocardium and is upregulated in heart failure. Although GRK5 is a critical regulator of cardiac G protein-coupled receptor signaling, recent data has uncovered noncanonical activity of GRK5 within nuclei that plays a key role in pathological hypertrophy. Targeted cardiac elevation of GRK5 in mice leads to exaggerated hypertrophy and early heart failure after transverse aortic constriction (TAC) because of GRK5 nuclear accumulation.In this study, we investigated the role of GRK5 in physiological, swimming-induced hypertrophy (SIH).Cardiac-specific GRK5 transgenic mice and nontransgenic littermate control mice were subjected to a 21-day high-intensity swim protocol (or no swim sham controls). SIH and specific molecular and genetic indices of physiological hypertrophy were assessed, including nuclear localization of GRK5, and compared with TAC. Unlike after TAC, swim-trained transgenic GRK5 and nontransgenic littermate control mice exhibited similar increases in cardiac growth. Mechanistically, SIH did not lead to GRK5 nuclear accumulation, which was confirmed in vitro as insulin-like growth factor-1, a known mediator of physiological hypertrophy, was unable to induce GRK5 nuclear translocation in myocytes. We found specific patterns of altered gene expression between TAC and SIH with GRK5 overexpression. Further, SIH in post-TAC transgenic GRK5 mice was able to preserve cardiac function.These data suggest that although nuclear-localized GRK5 is a pathological mediator after stress, this noncanonical nuclear activity of GRK5 is not induced during physiological hypertrophy.
Reversible High-Grade Atrioventricular Block Associated With Cocaine Use
Authors: Philip S. Hall, Babak Nazer, Randall J. Lee
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Critique of ‘The physical activity myth’ paper: discussion of flawed logic and inappropriate use of evidence
Authors: Paul Kelly, Graham Baker, Chloe McAdam, Karen Milton, Justin Richards, Charlie Foster, Marie Murphy, Nanette Mutrie
Journal: British Journal of Sports Medicine (2015)

We read the recent Editorial “It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet”1 with interest. While discussion about prevention and treatment of obesity is vital, we feel this piece did not make a positive contribution to ongoing scientific debate.

We understand that the Editorial was written to be provocative, but are concerned about the potential damage of misleading and extreme opinions on issues of public health. We believe that there are serious flaws in the interpretation, understanding and reasoning that should not go unchecked.

We highlight four points to demonstrate these flaws, rebut the assertions of the authors, and show why the debate on physical activity (PA) and obesity should disregard the Editorial.

1. Title: “The myth of physical inactivity and obesity”

What myth are the authors referring to? This should be outlined, explaining whether this is authors’ opinion, or can be evidenced in some way. Further, much of the content is unrelated to this title. It is imperative that a title reflects the content of a piece of scientific work whether it is opinion …