tbuckley/cabot-search huggingface dataset:
Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b–infected Japanese patients with or without cirrhosis
Authors: Hiromitsu Kumada, Kazuaki Chayama, Lino Rodrigues, Fumitaka Suzuki, Kenji Ikeda, Hidenori Toyoda, Ken Sato, Yoshiyasu Karino, Yasushi Matsuzaki, Kiyohide Kioka, Carolyn Setze, Tami Pilot‐Matias, Meenal Patwardhan, Regis A. Vilchez, Margaret Burroughs, Rebecca Redman
Journal: Hepatology (2015)

GIFT‐I is a phase 3 trial evaluating the efficacy and safety of a 12‐week regimen of coformulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) for treatment of Japanese hepatitis C virus genotype 1b–infected patients. It consists of a double‐blind, placebo‐controlled substudy of patients without cirrhosis and an open‐label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once‐daily OBV/PTV/r (25 mg/150 mg/100 mg; group A) or placebo (group B). Patients with cirrhosis received open‐label OBV/PTV/r (group C). The primary efficacy endpoint was the rate of sustained virological response 12 weeks posttreatment in interferon‐eligible, treatment‐naive patients without cirrhosis and hepatitis C virus RNA ≥100,000 IU/mL in group A. A total of 321 patients without cirrhosis were randomized and dosed with double‐blind study drug (106 received double‐blind placebo and later received open‐label OBV/PTV/r), and 42 patients with cirrhosis were enrolled and dosed with open‐label OBV/PTV/r. In the primary efficacy population, the rate of sustained virological response 12 weeks posttreatment was 94.6% (106/112, 95% confidence interval 90.5‐98.8). Sustained virological response 12 weeks posttreatment rates were 94.9% (204/215) in group A, 98.1% (104/106) in group B (open‐label), and 90.5% (38/42) in group C. Overall, virological failure occurred in 3.0% (11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0%‐2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis. Conclusion : In this broad hepatitis C virus genotype 1b–infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile. (H epatology 2015;62:1037‐1046)
Effects of nasal CPAP on simulated driving performance in patients with obstructive sleep apnoea
Authors: C. F. George, A. C. Boudreau, A. Smiley
Journal: Thorax (1997)

BACKGROUND: Many patients with obstructive sleep apnoea (OSA) have difficulty in driving and experience increased automobile accidents. It has previously been shown that patients with OSA perform poorly on a laboratory based divided attention driving test (DADT). METHODS: Seventeen men with OSA of mean (SD) age 49.7 (11.2) years and an initial apnoea/hypopnoea index (AHI) of 73.0 (28.9) were restudied from one to 12 (mean (SD) 9.2 (4.2)) months after initiating treatment with nasal continuous positive airway pressure (CPAP) to examine the effects of treatment on DADT performance. Eighteen age and sex matched controls were also retested 8.4 (3.4) months after their initial tests. Following a practice session, all subjects were given the DADT for 20 minutes before each daytime nap of the standard multiple sleep latency test (MSLT). RESULTS: Untreated patients with OSA, who performed much worse than controls in all measures, improved significantly on all measures of performance, particularly in tracking error which returned to the level of controls in all but one patient. Changes in performance were much greater for patients with OSA than for controls in tracking error (mean difference 106 (95% CI 75 to 135) cm), sleep latency/ MSLT (5.3 (95% CI 2.7 to 8.0) min), number of correct responses (1.2 (95% CI 0.4 to 1.9)), number of missed responses (1.7 (95% CI 0.9 to 2.3)), and number out of bounds (10.0 (95% CI 7.9 to 13.6)), but not for response time (0.1 (95% CI -0.3 to 0.2) s). Improvement in tracking error was highly correlated with improvement in sleepiness (r = 0.65). CONCLUSIONS: Impairment in laboratory driving performance skills in patients with OSA is reversed by successful treatment with nasal CPAP. Changes in daytime sleepiness account for some but not all of the improvement.
Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non–Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial
Authors: Roy S. Herbst, Anne-Marie Maddox, Mace L. Rothenberg, Eric J. Small, Eric H. Rubin, Jose Baselga, Federico Rojo, Waun Ki Hong, Helen Swaisland, Steven D. Averbuch, Judith Ochs, Patricia Mucci LoRusso
Journal: Journal of Clinical Oncology (2002)

To investigate safety, tolerability, dose-related pharmacologic properties, and pharmacodynamics of ZD1839 (gefinitib, Iressa; AstraZeneca Pharmacueticals, Wilmington, DE), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with solid tumor types known to express or highly express EGFR.This was an open-label, phase I, dose escalation safety/tolerability trial of oral ZD1839 (150 to 1,000 mg/d), administered once daily for 28-continuous-day cycles until disease progression or undue toxicity.Of 71 (69 assessable for safety; 58 for efficacy) patients at seven dose levels, most had non-small-cell lung (n = 39) or head and neck (n = 18) cancer, and 68 of 71 patients received prior cancer therapy (two or more regimens in 54 patients [78%]). Diarrhea and rash, the primary dose-limiting toxicities (DLTs), occurred at 800 mg. Frequent treatment-related grade 1/2 adverse events were diarrhea (55%), asthenia (44%), and acne-like follicular rash (46%). At doses >or= 800 mg, 45% of patients required dose reductions. No increased or cumulative toxicity was observed over 250 patient-months of exposure. Pharmacokinetic analysis showed that steady-state occurred by day 7, interpatient exposure was more variable than intrapatient exposure, and variability of exposure did not change with dose. One patient experienced a partial response, but antitumor activity manifested mainly as prolonged stable disease (45% of patients >or= 3 months, 22% >or= 6 months, and 7.2% >or= 1 year). No relationship between dose, response, or duration on study was observed.Rash and diarrhea, generally mild and tolerable at doses <or= 600 mg/d, were DLTs at 800 mg/d (maximum-tolerated dose). Antitumor activity was observed at all doses. Pharmacokinetic analyses confirmed suitability of once-daily oral dosing.
Angiotensin II Binding to Renomedullary Interstitial Cells Is Regulated by Osmolality
Authors: CHRISTINE MARIC, DAVID CASLEY, PETER J. HARRIS, DAINE ALCORN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Angiotensin II (Ang II) AT 1A receptors are localized to renomedullary interstitial cells (RMIC) in the inner stripe of the outer medulla but not in the inner medulla. Thus, there seems to be a correlation between decreases in AT 1A receptor binding to RMIC and increases in interstitial osmolality, suggesting that osmolality is important in determining Ang II binding to RMIC. Cultured RMIC were incubated in media of differing osmolalities (330, 630, 930, and 1230 mOsm/kgH 2 O). 125 I-[Sar 1 , Ile 8 ] Ang II binding to AT 1A receptors on RMIC grown in hyperosmolal media (930 mOsm/kgH 2 O) was reduced compared with isoosmolal (330 mOsm/kgH 2 O) media and was progressively reduced with further increases of osmolality. Similar studies were performed using bradykinin (BK) as a control peptide. Binding of the BK receptor ligand 125 I-[HPP-Hoe 140] to B 2 receptors was not affected by varying osmolality of the media. Reverse transcriptase-PCR demonstrated the presence of the mRNA expression for both AT 1A and B 2 receptors at each osmolality. The conclusion is that osmolality modulates Ang II binding to RMIC; in these cells, this phenomenon is restricted to Ang II as BK binding is not affected. Osmolality-induced changes in Ang II binding may modulate the actions of this peptide on RMIC and provide an important mechanism by which these cells modulate renal medullary function.
A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells and CD138 activates NK cells and has potent antitumor activity against human multiple myeloma in vitro and in vivo
Authors: Elke Pogge von Strandmann, Hinrich P. Hansen, Katrin S. Reiners, Roland Schnell, Peter Borchmann, Sabine Merkert, Venkateswara R. Simhadri, Andreas Draube, Marcel Reiser, Ingvill Purr, Michael Hallek, Andreas Engert
Journal: Blood (2005)
The Impact of Peripheral Arterial Disease on Outcome After Percutaneous Transluminal Angioplasty for Arteriovenous Fistula: A 1-Year Retrospective Analysis
Authors: Mustafa M Balcı, İsmail Kırbaş, Alper Kırkpantur, Aysel Türkvatan, Ugur Arslan, Okan Er, Kevser G Balcı, İbrahim Kocaoğlu, Sadık K Açıkgöz
Journal: Journal of the American College of Cardiology (2013)
Fulfilling the promise of primary care spirometry
Authors: P. Calverley
Journal: European Respiratory Journal (2007)

It is a truth universally acknowledged that the simplest and most reliable way of assessing the function of the lungs is to make a spirometric measurement. Well, perhaps not universally acknowledged, but there is an increasing acceptance that the diagnosis of many lung diseases should involve a measurement of the functional capacity of the respiratory system and although this does not always tell us the whole truth 1, 2, it represents a substantial improvement on diagnostic criteria based solely on history examination and plain chest radiography. This is particularly true for diseases associated with airflow obstruction, such as chronic obstructive pulmonary disease (COPD), and those involving restriction of the lungs or chest wall, such as idiopathic pulmonary fibrosis or kyphoscoliosis. For doctors in primary care, the former is much more likely to be seen than the latter, and COPD along with bronchial asthma constitute the most frequent chronic respiratory diseases in this setting. While the importance of making an accurate diagnosis is not in doubt for patients with diabetes or chronic renal failure, we have been slow to adopt a similarly rigorous approach to respiratory conditions, especially COPD. Thanks to the efforts of many organisations, especially the European Respiratory Society (ERS) and the American Thoracic Society (ATS) 3, and also the Global Initiative for Chronic Obstructive Lung Disease (GOLD) programme 4, there is now a much wider appreciation of the need for objective diagnosis in common conditions such as COPD. As recent data from the Burden of Obstructive Lung Disease initiative has shown 5, this is a frequent and underappreciated problem, not only in developed European countries but particularly in many developing countries. One of our major tasks for the next decade will be to produce clear and consistent guidance as to how the relatively …
Vitamin B<sub>12</sub>supplementation improves rates of sustained viral response in patients chronically infected with hepatitis C virus
Authors: Alba Rocco, Debora Compare, Pietro Coccoli, Ciro Esposito, Antimo Di Spirito, Antonio Barbato, Pasquale Strazzullo, Gerardo Nardone
Journal: Gut (2012)

<h3>Background</h3> In vitro, vitamin B<sub>12</sub> acts as a natural inhibitor of hepatitis C virus (HCV) replication. <h3>Objective</h3> To assess the effect of vitamin B<sub>12</sub> on virological response in patients with chronic HCV hepatitis naïve to antiviral therapy. <h3>Methods</h3> Ninety-four patients with chronic HCV hepatitis were randomly assigned to receive pegylated interferon α plus ribavirin (standard-of-care; SOC) or SOC plus vitamin B<sub>12</sub> (SOC+B<sub>12</sub>). Viral response—namely, undetectable serum HCV-RNA, was evaluated 4 weeks after starting treatment (rapid viral response), 12 weeks after starting treatment (complete early viral response) and 24 or 48 weeks after starting treatment (end-of-treatment viral response) and 24 weeks after completing treatment (sustained viral response (SVR)). Genotyping for the interleukin (<i>IL</i>)<i>-28B</i> polymorphism was performed a posteriori in a subset (42/64) of HCV genotype 1 carriers. <h3>Results</h3> Overall, rapid viral response did not differ between the two groups, whereas the rates of complete early viral response (p=0.03), end-of-treatment viral response (p=0.03) and SVR (p=0.001) were significantly higher in SOC+B<sub>12</sub> patients than in SOC patients. In SOC+B<sub>12</sub> patients, the SVR rate was also significantly higher in carriers of a difficult-to-treat genotype (p=0.002) and in patients with a high baseline viral load (p=0.002). Distribution of genotype <i>IL-28B</i> did not differ between the two groups. At multivariate analysis, only easy-to-treat HCV genotypes (OR=9.00; 95% CI 2.5 to 37.5; p=0.001) and vitamin B<sub>12</sub> supplementation (OR=6.9; 95% CI 2.0 to 23.6; p=0.002) were independently associated with SVR. <h3>Conclusion</h3> Vitamin B<sub>12</sub> supplementation significantly improves SVR rates in HCV-infected patients naïve to antiviral therapy.
Spontaneous action potentials of cells in the canine sinus node.
Authors: W T Woods, F Urthaler, T N James
Journal: Circulation Research (1976)

Right atria were excised from the hearts of 20 young dogs (15 +/- 5 weeks old) and maintained in vitro in order to perform microelectrode impalements. The atria contracted spontaneously for at least 6 hours at a stable rate of 127/min when they were perfused with Krebs-Ringer bicarbonate solution through the sinus node artery. Cells within a small area near the sinus node artery and between the superior vena cava and right atrium consistently yielded transmembrane potentials typical of pacemaker cells. This area was verified histologically to be the midportion of the sinus node. Electrical characteristics of these sinus node pacemaker cells were: maximum diastolic potential, -56 +/- 7 mV (mean +/- 1 SD); action potential amplitude, 56 +/- 8 mV; overshoot, 0 +/- 2 mV. Smooth transitions from phase 4 to phase 0 were always present. From these experiments we conclude that the excised perfused canine right atrium provides a useful new experimental cardiac preparation because it maintains stable spontaneous activity for many hours in vitro and the sinus node within it is readily accessible for study by intracellular microelectrodes.
Refractory asthma in elderly patients in the UK
Authors: Rekha Chaudhuri, Charles McSharry, Liam Heaney, Robert Niven, Christopher Brightling, Andrew Menzies-Gow, Christine Bucknall, Adel Mansur, Wai-Ting Nicola Lee, Malcolm Shepherd, Mark Spears, Neil Thomson
Journal: European Respiratory Journal (2013)

BACKGROUND   Severe refractory asthma affects all age-groups including the elderly. We examined the effect of age on clinical and inflammatory outcomes in patients recruited to the British Thoracic Society [BTS] Severe Asthma Registry.   METHODS   All subjects with refractory asthma [ATS criteria] ≥18 years old from the BTS Severe Asthma Registry were included in the analysis.   RESULTS   754 subjects with refractory asthma were studied. Age was normally distributed (mean of 49.4 yrs [SD 13.6], range 18-82 yrs). Age correlated with a lower number of unscheduled emergency visits [-0.137; p=0.000], hospital admissions [r = -0.147; p=0.000], ITU admissions [r = -0.095; p=0.010], but asthma control was not affected [ACQ or ACT scores]. FEV 1  % predicted was lower with increasing age. Comparison of clinical and inflammatory outcomes in patients aged    CONCLUSION   Elderly patients with refractory asthma have poor symptom control and asthma quality of life, at levels similar to younger patients with refractory asthma. However, the number of severe exacerbations and unscheduled emergency visits is slightly less in the elderly group.
Association of Agent Orange With Plasma Cell Disorder
Authors: Nikhil C. Munshi
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Frequent Assimilation of Mitochondrial DNA by Grasshopper Nuclear Genomes
Authors: Douda Bensasson, De-Xing Zhang, Godfrey M. Hewitt
Journal: Molecular Biology and Evolution (2000)

Multiple copies of mitochondrial-like DNA were found in the brown mountain grasshopper, Podisma pedestris (Orthoptera: Acrididae), paralogous to COI and ND5 regions. The same was discovered using the ND5 regions of nine other grasshopper species from four separate subfamilies (Podisminae, Calliptaminae, Cyrtacanthacridinae, and Gomphocerinae). The extra ND5-like sequences were shown to be nuclear in the desert locust, Schistocerca gregaria (Cyrtacanthacridinae), and probably so in P. pedestris and an Italopodisma sp. (Podisminae). Eighty-seven different ND5-like nuclear mitochondrial pseudogenes (Numts) were sequenced from 12 grasshopper individuals. Different nuclear mitochondrial pseudogenes, if descended from the same mitochondrial immigrant, will have diverged from each other under no selective constraints because of their loss of functionality. Evidence of selective constraints in the differences between any two Numt sequences (e.g., if most differences are at third positions of codons) implies that they have separate mitochondrial origins. Through pairwise comparisons of pseudogene sequences, it was established that there have been at least 12 separate mtDNA integrations into P. pedestris nuclear genomes. This is the highest reported rate of horizontal transfer between organellar and nuclear genomes within a single animal species. The occurrence of numerous mitochondrial pseudogenes in nuclear genomes derived from separate integration events appears to be a common phenomenon among grasshoppers. More than one type of mechanism appears to have been involved in generating the observed grasshopper Numts.
Malaria in the United Kingdom
Authors: L. J. Bruce-Chwatt, B. A. Southgate, C. C. Draper
Journal: BMJ (1974)

Over the past decade the United Kingdom had the second highest number of cases of imported malaria among European countries. There has been a substantial rise in recorded cases of malaria during the past three years though some of it may be due to improved notification. Fatal cases of malaria in visitors to Africa have averaged 6.5% of reported infections due to Plasmodium falciparum. Attacks of vivax malaria may occur several months after travellers return from a malarious country.
Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation
Authors: Atsutaka Kubosaki, Yasuhiro Tomaru, Michihira Tagami, Erik Arner, Hisashi Miura, Takahiro Suzuki, Masanori Suzuki, Harukazu Suzuki, Yoshihide Hayashizaki
Journal: Genome biology (2009)

Immediate early genes are considered to play important roles in dynamic gene regulatory networks following exposure to appropriate stimuli. One of the immediate early genes, early growth response gene 1 (EGR-1), has been implicated in differentiation of human monoblastoma cells along the monocytic commitment following treatment with phorbol ester. EGR-1 has been thought to work as a modifier of monopoiesis, but the precise function of EGR-1 in monocytic differentiation has not been fully elucidated.We performed the first genome-wide analysis of EGR-1 binding sites by chromatin immunoprecipitation with promoter array (ChIP-chip) and identified EGR-1 target sites in differentiating THP-1 cells. By combining the results with previously reported FANTOM4 data, we found that EGR-1 binding sites highly co-localized with CpG islands, acetylated histone H3 lysine 9 binding sites, and CAGE tag clusters. Gene Ontology (GO) analysis revealed enriched terms, including binding of molecules, in EGR-1 target genes. In addition, comparison with gene expression profiling data showed that EGR-1 binding influenced gene expression. Moreover, observation of in vivo occupancy changes of DNA binding proteins following PMA stimulation indicated that SP1 binding occupancies were dramatically changed near EGR-1 binding sites.We conclude that EGR-1 mainly recognizes GC-rich consensus sequences in promoters of active genes. GO analysis and gene expression profiling data confirm that EGR-1 is involved in initiation of information transmission in cell events. The observations of in vivo occupancy changes of EGR-1 and SP1 suggest that several types of interplay between EGR-1 and other proteins result in multiple responses to EGR-1 downstream genes.
Chimera Analysis of Troponin I Domains That Influence Ca <sup>2+</sup> -Activated Myofilament Tension in Adult Cardiac Myocytes
Authors: Margaret V. Westfall, Faris P. Albayya, Immanuel I. Turner, Joseph M. Metzger
Journal: Circulation Research (2000)

Abstract —The goal of this study was to investigate isoform-specific functional domains of the inhibitory troponin subunit, troponin I (TnI), as it functions within the intact myofilaments of adult cardiac myocytes. Adenovirus-mediated gene transfer was used to deliver and express a TnI chimera composed of the amino terminus of cardiac TnI (cTnI) and the carboxy terminus of slow skeletal TnI (ssTnI) in adult rat cardiac myocytes. The TnI chimera, designated N-card/slow-C TnI, was expressed and incorporated into myofilaments after gene transfer, without detectable changes in contractile protein stoichiometry or sarcomere architecture. Interestingly, force at submaximal Ca 2+ levels was markedly elevated in single permeabilized myocytes expressing the N-card/slow-C TnI chimera relative to force generated in adult myocytes expressing ssTnI or cTnI. Based on these results, a hierarchy of myofilament Ca 2+ sensitivity is emerging by use of TnI chimera analysis, with the order of sensitivity being N-card/slow-C TnI≫ssTnI≫cTnI. These results also strongly suggest that independent isoform-specific domains in both the amino and carboxy portions of TnI influence myofilament Ca 2+ sensitivity. In additional studies carried out under pathophysiological ionic conditions (pH 6.2), the dramatic acidosis-induced decrease in myofilament Ca 2+ sensitivity observed in myocytes expressing cTnI was blunted in myocytes expressing N-card/slow-C TnI in a manner similar to that in ssTnI-expressing myocytes. These results demonstrate that there is a pH-sensitive domain residing in the carboxy-terminal portion of TnI. The dissection of isoform-specific functional domains under physiological and acidic pH conditions demonstrates the utility of TnI chimeras for analysis of TnI function and provides important insights into the overall function of TnI within the intact myofilament of adult cardiac myocytes.