tbuckley/cabot-search huggingface dataset:
Importance of Geometry and Refractory Period in Sustaining Atrial Fibrillation
Authors: Gregory D. Byrd, Sandip M. Prasad, Crystal M. Ripplinger, T. Ryan Cassilly, Richard B. Schuessler, John P. Boineau, Ralph J. Damiano
Journal: Circulation (2005)

Background— The critical mass hypothesis for atrial fibrillation (AF) was proposed in 1914. There has never been a systematic investigation defining the relationship between tissue geometry and AF. The purpose of this study was to determine the association among the probability of maintaining AF and the width, area, weight, effective refractory period (ERP), and wavelength in atrial tissue. Methods and Results— Isolated canine atria (n=20) were perfused with Krebs-Henseleit solution. Baseline ERPs were obtained with and without acetylcholine (10E-3.5 mol/L) using single extra-stimulus pacing while unipolar electrograms were recorded from 250 sites. The tissue was then partitioned using bipolar radiofrequency ablation, and the ERPs were measured again with and without acetylcholine. Any section of tissue that maintained AF was divided until the arrhythmia was no longer inducible. ERPs and conduction velocities were measured in all of the sections after each ablation, and the wavelengths were calculated. The probability of AF was found to be correlated with increasing tissue areas, widths, and weights ( P &lt;0.001). The probability of AF was significantly associated with the length of the ERP and the wavelength ( P &lt;0.001). With shorter ERPs and shorter wavelengths, there was an increased probability of sustained AF. Conclusions— The probability of sustained AF was significantly associated with increasing tissue area, width, and weight and decreasing ERPs and wavelengths. These data may lead to a better understanding of the mechanism of AF and, thus, help to design more-effective interventional procedures in the future.
Targeting β-Transducin Repeat–Containing Protein E3 Ubiquitin Ligase Augments the Effects of Antitumor Drugs on Breast Cancer Cells
Authors: Weigang Tang, Ying Li, Duonan Yu, Andrei Thomas-Tikhonenko, Vladimir S. Spiegelman, Serge Y. Fuchs
Journal: Cancer Research (2005)

Abstract β-Transducin repeat–containing proteins (β-TrCP) serve as substrate recognition component of E3 ubiquitin ligases that control stability of important regulators of cell cycle and signal transduction. β-TrCP function is essential for the induction of nuclear factor κB transcriptional activities, which play a key role in proliferation and survival of cancer cells and are often constitutively up-regulated in human breast cancers. Here we show that inhibition of β-TrCP either by RNAi approach or by forced expression of a dominant-negative β-TrCP mutant suppresses growth and survival of human breast cancer cells. In addition, inhibition of β-TrCP augments the antiproliferative effects of anticancer drugs such as doxorubicin, tamoxifen, and paclitaxel on human mammary tumor cells. These data provide the proof of principle that targeting β-TrCP might be beneficial for anticancer therapies.
Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris.
Authors: P Wagniart, R J Ferguson, B R Chaitman, F Achard, A Benacerraf, B Delanguenhagen, B Morin, A Pasternac, M G Bourassa
Journal: Circulation (1982)

Diltiazem is a calcium slow-channel blocking drug that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy 3 hours after a single oral dose of 120 mg, 12 men with chronic stable angina pectoris performed a maximal exercise test on a bicycle ergometer after ingesting either placebo or diltiazem administered in a double-blind fashion. During submaximal exercise at a fixed work load, diltiazem decreased the average heart rate response from 119 +/- 17 to 107 +/- 14 beats/min (p less than 0.01), systolic blood pressure from 182 +/- 15 to 175 +/- 15 mm Hg (p less than 0.05) and the rate-pressure product from 21.8 +/- 4.2 to 18.8 +/- 3.2 x 10(-3) units (p less than 0.01). The average submaximal work load at which significant ST-segment depression (0.1 mV) first appeared was increased from 355 +/- 142 to 525 +/- 143 seconds (p less than 0.01) after diltiazem. At peak exercise after diltiazem, the average depth of ST-segment depression in any one lead and the extent of myocardial ischemia observed in all 12 ECG leads were decreased (p less than 0.01), even though the average work load was increased by 29% (p less than 0.01). Peak heart rate, systolic blood pressure and rate-pressure product were similar with placebo and diltiazem. The plasma diltiazem concentration was 13.9 +/- 29 ng/ml 3 hours after ingestion and was significantly (p less than 0.05) related to the increased time to the onset of important ST-segment depression (r = 0.65) and to the decrease in the extent of myocardial ischemia observed in all 12 ECG leads (r = -0.61) compared with placebo. Thus, diltiazem is effective in treating chronic stable angina pectoris. It decreases myocardial oxygen requirements during upright exercise and appears to increase myocardial oxygen delivery.
Physiotherapy intervention late after stroke and mobility.
Authors: D. T. Wade, F. M. Collen, G. F. Robb, C. P. Warlow
Journal: BMJ (1992)

OBJECTIVE--To determine whether the intervention of a physiotherapist improved mobility in patients seen more than one year after stroke. DESIGN--Randomised crossover trial comparing two groups offered intervention by a physiotherapist, one immediately after entry into the trial and the other after a delay of three months. The intervention consisted of identifying problems and offering advice and help to solve the problems. SETTING--Patients9 homes in Oxfordshire. SUBJECTS--Patients who had reduced mobility due to a stroke more than one year before entry; 60 were recruited from a community stroke register and 34 in other ways. MAIN OUTCOME MEASURES--Standard measures of mobility including gait speed, functional ambulation categories, the Nottingham extended activities of daily living index, and individual items from the Barthel activities of daily living index and the Frenchay activities index. Measures of manual dexterity, depression, and anxiety were used as controls. RESULTS--94 patients entered the trial and 49 were randomised to immediate and 45 to delayed physiotherapy; 89 were compared at the crossover point. At randomisation the two groups were comparable. At three months the group given early therapy showed an improvement in gait speed whereas the untreated group had declined (differences of -3.9 v 6.4 s to walk 10 m; p less than 0.01); between three and six months the group given delayed therapy showed improvement and the previously treated group declined (differences of 6.5 v -3.9 s to walk 10 m; p less than 0.01). A 9% (95% confidence interval 0% to 18%) decrease in time taken to walk 10 m was associated with treatment and a 12% (2% to 19%) increase when patients were untreated. Other measures did not change significantly. CONCLUSION--Intervention of an experienced physiotherapist late after stroke specifically improves mobility, albeit by a small amount, but the effects do not seem to be maintained, perhaps because there is an underlying decline in mobility in these patients. Gait speed offers a simple and sensitive measure of outcome.
Position is everything?
Authors: Karl H. Pribram
Journal: Behavioral and Brain Sciences (1995)

Abstract Neurophysiological evidence consonant with F&amp;L's lambda model is reviewed and results of additional experiments are presented. The evidence shows that there are neurons in the motor cortex that respond to selective band widths of passive sinusoidal movements; the additional data show how, with movement, directionally sensitive population vectors can be shown to emerge from the data.
Cellular calcium homeostasis during ischemia; a thermodynamic approach
Authors: J Fiolet
Journal: Cardiovascular Research (2000)

The pivotal role of calcium cycling and homeostasis has long been recognized in contractile, metabolic, electrical and ionic alterations associated with myocardial ischemia and anoxia, as well as in hibernation, stunning and mitochondrial dysfunction associated with reperfusion. However, the lack of adequate techniques seriously hampered measurement of cellular calcium in the low and narrow range of physiological concentrations, particularly in the cytoplasm. Uninterrupted measurement of the dynamics of calcium in the cytoplasm and in organelles such as the sarcoplasmic reticulum and mitochondria proved impossible for a long time.

Bourdillon and Poole-Wilson [1] were the first to accomplish this goal in 1981. They devised an elegant technique to continuously monitor mechanical function, calcium uptake and release during ischemia and reperfusion using calcium isotopes and radioactive labeling of the extracellular space. Their basic observations (see below) attracted much attention and the study remains frequently cited. Since then, new techniques have become available, superior in sensitivity and time resolution, among which are intracellular calcium specific fluorescent indicators [2–4] and 19F NMR [5,6]. Consequently, an abundance of original papers and many review articles have been published over the last 2 decades addressing the issue of calcium handling during ischemia and reperfusion.

It is beyond the scope of this short update to present a full record of all literature on calcium handling during ischemia, anoxia and reperfusion over the past 2 decades. For an overview of the reperfusion related literature the reader is referred to recent review articles dealing with: the role of the Na/H-exchanger [7–9], mitochondria [10–12], sarcoplasmic reticulum [13], e–c-coupling in stunning [14], hibernation [15] and clinical implications [16].

The aim of the present contribution is to put the available data on calcium handling and homeostasis during ischemia and anoxia in a thermodynamic perspective with particular emphasis …
RUBELLA INFECTION OF SYNOVIAL CELLS AND THE RESISTANCE OF CELLS DERIVED FROM PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Arthur I. Grayzel, Carolyn Beck
Journal: The Journal of Experimental Medicine (1970)

The mechanism of growth stimulation in allogeneic lymphocytes mixed in vitro was studied at the cell level by means of cytophotometric techniques. A pronounced increase in fluorescence intensity of fixed and acridine orange (AO) stained lymphocytes was observed as soon as after 1-3 hr in mixed culture. No increase in the amount of DNA took place during this time. The higher fluorescence intensity was due to an increased accessibility of AO binding sites in the deoxyribonucleoprotein (DNP) complex, most probably as a result of weakened bonds between the DNA and the protein moiety in the DNP complex. Similar DNP changes have been found in other systems of growth stimulation and may be one prerequisite for later induction of cellular synthetic processes. Increased AO binding only occurred when the lymphocyte donors were incompatible at the major histocompatibility locus (HL-A); there was no change in AO binding in cases of HL-A identity. The AO binding reaction probably reflects a specific recognition of HL-A antigens, whereas other antigenic discrepancies between the individuals do not seem to cause an analogous response.
Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity
Authors: Jennifer T. Grier, Lisa R. Forbes, Linda Monaco-Shawver, Jennifer Oshinsky, T. Prescott Atkinson, Curtis Moody, Rahul Pandey, Kerry S. Campbell, Jordan S. Orange
Journal: Journal of Clinical Investigation (2012)

The Fc receptor on NK cells, FcγRIIIA (CD16), has been extensively studied for its role in mediating antibody-dependent cellular cytotoxicity (ADCC). A homozygous missense mutation in CD16 (encoding a L66H substitution) is associated with severe herpesvirus infections in rare patients. Here, we identified a new patient with this CD16 mutation and compared the patient's NK cells to those of the originally reported patient. Patients with the L66H mutation had intact ADCC, but deficient spontaneous NK cell cytotoxicity and decreased surface expression of CD2, a coactivation receptor. Mechanistic studies in a human NK cell line, NK-92, demonstrated that CD16 expression correlated with CD2 surface levels and enabled killing of a melanoma cell line typically resistant to CD16-deficient NK-92 cells. An association between CD16 and CD2 was identified biochemically and at the immunological synapse, which elicited CD16 signaling after CD2 engagement. Stable expression of CD16 L66H in NK-92 cells recapitulated the patient phenotype, abrogating association of CD16 with CD2 as well as CD16 signaling after CD2 ligation. Thus, CD16 serves a role in NK cell-mediated spontaneous cytotoxicity through a specific association with CD2 and represents a potential mechanism underlying a human congenital immunodeficiency.
Neutralized Nanoparticle Composed of SS‐Cleavable and pH‐Activated Lipid‐Like Material as a Long‐Lasting and Liver‐Specific Gene Delivery System
Authors: Masami Ukawa, Hidetaka Akita, Yasuhiro Hayashi, Ryohei Ishiba, Kota Tange, Masaya Arai, Kazuhiro Kubo, Yuriko Higuchi, Kazunori Shimizu, Satoshi Konishi, Mitsuru Hashida, Hideyoshi Harashima
Journal: Advanced Healthcare Materials (2014)

Charge-neutralized lipid envelope-type nanoparticles formed with SS-cleavable and pH-activated lipid-like materials (ssPalm) accumulate rapidly in the liver without forming aggregates in the blood circulation, and result in a liver-specific gene expression for a long duration (>2 weeks) with neither immunological responses nor hepatotoxicity after intraveneous administration, when it carries pDNA free from CpG-motifs.
Outcomes of Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer: A Proposal for Patient Selection
Authors: Toyomi Satoh, Masayuki Hatae, Yoh Watanabe, Nobuo Yaegashi, Osamu Ishiko, Shoji Kodama, Satoshi Yamaguchi, Kazunori Ochiai, Masashi Takano, Harushige Yokota, Yosuke Kawakami, Sadako Nishimura, Daiki Ogishima, Shunsuke Nakagawa, Hiroaki Kobayashi, Tanri Shiozawa, Toru Nakanishi, Toshiharu Kamura, Ikuo Konishi, Hiroyuki Yoshikawa
Journal: Journal of Clinical Oncology (2010)

Purpose The objective of this study was to assess clinical outcomes and fertility in patients treated conservatively for unilateral stage I invasive epithelial ovarian cancer (EOC). Patients and Methods A multi-institutional retrospective investigation was undertaken to identify patients with unilateral stage I EOC treated with fertility-sparing surgery. Favorable histology was defined as grade 1 or grade 2 adenocarcinoma, excluding clear cell histology. Results A total of 211 patients (stage IA, n = 126; stage IC, n = 85) were identified from 30 institutions. Median duration of follow-up was 78 months. Five-year overall survival and recurrence-free survival were 100% and 97.8% for stage IA and favorable histology (n = 108), 100% and 100% for stage IA and clear cell histology (n = 15), 100% and 33.3% for stage IA and grade 3 (n = 3), 96.9% and 92.1% for stage IC and favorable histology (n = 67), 93.3% and 66.0% for stage IC and clear cell histology (n = 15), and 66.7% and 66.7% for stage IC and grade 3 (n = 3). Forty-five (53.6%) of 84 patients who were nulliparous at fertility-sparing surgery and married at the time of investigation gave birth to 56 healthy children. Conclusion Our data confirm that fertility-sparing surgery is a safe treatment for stage IA patients with favorable histology and suggest that stage IA patients with clear cell histology and stage IC patients with favorable histology can be candidates for fertility-sparing surgery followed by adjuvant chemotherapy.
Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema
Authors: I. Ferrarotti, M. Zorzetto, M. Beccaria, L.S. Gilè, R. Porta, N. Ambrosino, P.F. Pignatti, I. Cerveri, E. Pozzi, M. Luisetti
Journal: European Respiratory Journal (2003)

Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). Tumour necrosis factor (TNF) family genes have been widely investigated but inconsistent results may lie either in the genetic heterogeneity of populations or in the poor phenotype definition. A genetic study was performed using a narrower phenotype of COPD. The authors studied 86 healthy smokers and 63 COPD subjects who were enrolled based on irreversible airflow obstruction (forced expiratory volume in one second/forced vital capacity &lt;70% predicted) and a diffusing capacity for carbon monoxide &lt;50% predicted (moderate-to-severe COPD associated with pulmonary emphysema). The following polymorphisms were investigated: TNF-308, the biallelic polymorphism located in the first intron of the lymphotoxin‐α gene, and exon 1 and exon 6 of the TNF receptor 1 and 2 genes, respectively. No significant deviations were found concerning the four polymorphisms studied between the two populations. The authors confirm that the tumour necrosis factor family genes, at least for the polymorphisms investigated, are not major genetic risk factors for chronic obstructive pulmonary disease in Caucasians, either defined in terms of emphysema (this study) or airflow obstruction (previous studies). Nevertheless, the authors would like to emphasise the importance of narrowing the phenotype in the search for genetic risk factors in chronic obstructive pulmonary disease.
Mucus Clearance and Lung Function in Cystic Fibrosis with Hypertonic Saline
Authors: Scott H. Donaldson, William D. Bennett, Kirby L. Zeman, Michael R. Knowles, Robert Tarran, Richard C. Boucher
Journal: New England Journal of Medicine (2006)

Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense. Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function.A total of 24 patients with cystic fibrosis were randomly assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent sodium chloride) four times daily with or without pretreatment with amiloride. Mucus clearance and lung function were measured during 14-day baseline and treatment periods.Long-term inhalation of hypertonic saline without pretreatment with amiloride (i.e., with placebo pretreatment) resulted in a sustained (> or =8 hours) increase in 1-hour rates of mucus clearance, as compared with those with amiloride pretreatment (14.0+/-2.0 vs. 7.0+/-1.5 percent, respectively; P=0.02) and increased 24-hour rates of mucus clearance over baseline. Furthermore, inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second (FEV1) between the baseline period and the treatment period (mean difference, 6.62 percent; 95 percent confidence interval, 1.6 to 11.7; P=0.02), whereas hypertonic saline with amiloride did not improve FEV1 (mean difference, 2.9 percent; 95 percent confidence interval, -2.2 to 8.0; P=0.23). Forced vital capacity (FVC), the forced expiratory flow between 25 and 75 percent of FVC (FEF25-75), and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo, whereas the residual volume as a proportion of total lung capacity (RV:TLC) did not change in either group. A comparison of the changes in lung function in the two groups showed no significant difference. In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance, whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit.In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease.
The multiple causes of human SCID
Authors: Rebecca H. Buckley
Journal: Journal of Clinical Investigation (2004)

SCID, a syndrome characterized by the absence of T cells and adaptive immunity, can result from mutations in multiple genes that encode components of the immune system. Three such components are cytokine receptor chains or signaling molecules, five are needed for antigen receptor development, one is adenosine deaminase — a purine salvage pathway enzyme, and the last is a phosphatase, CD45. In this issue of the JCI, a report describes how complete deficiency of the CD3ε chain of the T cell antigen receptor/CD3 complex causes human SCID.
A Reengineered Hospital Discharge Program to Decrease Rehospitalization
Authors: Brian W. Jack
Journal: Annals of Internal Medicine (2009)

Emergency department visits and rehospitalization are common after hospital discharge.To test the effects of an intervention designed to minimize hospital utilization after discharge.Randomized trial using block randomization of 6 and 8. Randomly arranged index cards were placed in opaque envelopes labeled consecutively with study numbers, and participants were assigned a study group by revealing the index card.General medical service at an urban, academic, safety-net hospital.749 English-speaking hospitalized adults (mean age, 49.9 years).A nurse discharge advocate worked with patients during their hospital stay to arrange follow-up appointments, confirm medication reconciliation, and conduct patient education with an individualized instruction booklet that was sent to their primary care provider. A clinical pharmacist called patients 2 to 4 days after discharge to reinforce the discharge plan and review medications. Participants and providers were not blinded to treatment assignment.Primary outcomes were emergency department visits and hospitalizations within 30 days of discharge. Secondary outcomes were self-reported preparedness for discharge and frequency of primary care providers' follow-up within 30 days of discharge. Research staff doing follow-up were blinded to study group assignment.Participants in the intervention group (n = 370) had a lower rate of hospital utilization than those receiving usual care (n = 368) (0.314 vs. 0.451 visit per person per month; incidence rate ratio, 0.695 [95% CI, 0.515 to 0.937]; P = 0.009). The intervention was most effective among participants with hospital utilization in the 6 months before index admission (P = 0.014). Adverse events were not assessed; these data were collected but are still being analyzed.This was a single-center study in which not all potentially eligible patients could be enrolled, and outcome assessment sometimes relied on participant report.A package of discharge services reduced hospital utilization within 30 days of discharge.Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute, National Institutes of Health.