tbuckley/cabot-search huggingface dataset:
Lethal Injection for Execution: Chemical Asphyxiation?
Authors: Teresa A Zimmers, Jonathan Sheldon, David A Lubarsky, Francisco López-Muñoz, Linda Waterman, Richard Weisman, Leonidas G Koniaris
Journal: PLoS Medicine (2007)

Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended.We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest.We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable.
Angiotensin II Type 1 Receptor–Induced Extracellular Signal–Regulated Protein Kinase Activation Is Mediated by Ca <sup>2+</sup> /Calmodulin-Dependent Transactivation of Epidermal Growth Factor Receptor
Authors: Satoshi Murasawa, Yasukiyo Mori, Yoshihisa Nozawa, Noriko Gotoh, Masabumi Shibuya, Hiroya Masaki, Katsuya Maruyama, Yoshiaki Tsutsumi, Yasutaka Moriguchi, Yasunobu Shibazaki, Yohko Tanaka, Toshiji Iwasaka, Mitsuo Inada, Hiroaki Matsubara
Journal: Circulation Research (1998)

Abstract —The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of growth factor stimulation, and recent evidence suggests that G protein–coupled receptors transactivate growth factor receptors to transmit mitogenic effects. In the present study, we report the involvement of epidermal growth factor receptor (EGF-R) in Ang II–induced extracellular signal–regulated kinase (ERK) activation, c- fos gene expression, and DNA synthesis in cardiac fibroblasts. Ang II induced a rapid tyrosine phosphorylation of EGF-R in association with phosphorylation of Shc protein and ERK activation. Specific inhibition of EGF-R function by either a dominant-negative EGF-R mutant or selective tyrphostin AG1478 completely abolished Ang II–induced ERK activation. Induction of c- fos gene expression and DNA synthesis were also abolished by the inhibition of EGF-R function. Calmodulin or tyrosine kinase inhibitors, but not protein kinase C (PKC) inhibitors or downregulation of PKC, completely abolished transactivation of EGF-R by Ang II or the Ca 2+ ionophore A23187. Epidermal growth factor (EGF) activity in concentrated supernatant from Ang II–treated cells was not detected, and saturation of culture media with anti-EGF antibody did not affect the Ang II–induced transactivation of EGF-R. Conditioned media in which cells were incubated with Ang II could not induce phosphorylation of EGF-R on recipient cells. Platelet-derived growth factor-β receptor was not phosphorylated on Ang II stimulation, and Ang II–induced c- jun gene expression was not affected by tyrphostin AG1478. Our results demonstrated that in cardiac fibroblasts Ang II–induced ERK activation and its mitogenic signals are dominantly mediated by EGF-R transactivated in a Ca 2+ /calmodulin-dependent manner and suggested that the effects of Ang II on cardiac fibroblasts should be interpreted in association with the signaling pathways regulating cellular proliferation and/or differentiation by growth factors.
Combination Therapy Targeting Both Tumor-Initiating and Differentiated Cell Populations in Prostate Carcinoma
Authors: Anna Dubrovska, Jimmy Elliott, Richard J. Salamone, Sungeun Kim, Lindsey J. Aimone, John R. Walker, James Watson, Maira Sauveur-Michel, Carlos Garcia-Echeverria, Charles Y. Cho, Venkateshwar A. Reddy, Peter G. Schultz
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The cancer stem cell hypothesis predicts that standard prostate cancer monotherapy eliminates bulk tumor cells but not a tumor-initiating cell population, eventually leading to relapse. Many studies have sought to determine the underlying differences between bulk tumor and cancer stem cells. Experimental Design: Our previous data suggest that the PTEN/PI3K/AKT pathway is critical for the in vitromaintenance of CD133+/CD44+ prostate cancer progenitors and, consequently, that targeting PI3K signaling may be beneficial in treatment of prostate cancer. Results: Here, we show that inhibition of PI3K activity by the dual PI3K/mTOR inhibitor NVP-BEZ235 leads to a decrease in the population of CD133+/CD44+ prostate cancer progenitor cells in vivo. Moreover, the combination of the PI3K/mTOR modulator NVP-BEZ235, which eliminates prostate cancer progenitor populations, and the chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors in a prostate cancer xenograft model than monotherapy. Conclusion: This combination treatment ultimately leads to the expansion of cancer progenitors with a PTEN E91D mutation, suggesting that the analysis of PTEN mutations could predict therapeutic response to the dual therapy. Clin Cancer Res; 16(23); 5692–702. ©2010 AACR.
Sport specific fitness testing of elite badminton players.
Authors: M K Chin, A S Wong, R C So, O T Siu, K Steininger, D T Lo
Journal: British Journal of Sports Medicine (1995)

There is a scarcity of descriptive data on the performance capacity of elite badminton players, whose fitness requirements are quite specific. The purpose of this paper is to investigate the physiological response of elite badminton players in a sport-specific fitness test. Twelve Hong Kong national badminton team players performed a field test on a badminton court. Six light bulbs were connected to a programming device causing individual bulbs to light up in a given sequence. The players were instructed to react to the flashes by running towards them, and striking shuttles mounted in the vicinity of the bulbs. Exercise intensity was controlled by altering the interval between successive lightings. A low correlation (r = 0.65) was found between the results of the field test and the rank-order list of subjects, based on an objective on-field physiological assessment and subjective ranking. This may be explained by the requirements of other factors besides physical fitness which contribute to success in elite level badminton competition. These factors may include, for example, technical skill, mental power, and aesthetic judgements on the court. Maximum mean (s.d.) heart rate data (187(8) beats.min-1) and blood lactate values (10.4(2.9) mmol.l-1) in this study showed that players were under maximal load during the field test. From the testing data, it seems reasonable to speculate that the intensity of level 3 (20 light pulses.min-1; 3.0 s.pulse-1) and level 4 (22 light pulses.min-1; 2.7 s.pulse-1) simulates the requirement of actual games energy expenditure of the Hong Kong badminton players exercising at close to their anaerobic threshold. The results also show that an estimate of fitness can be derived from measurements involving exercise closely resembling that which is specific for the sports activity in question. Improved training advice and guidance may result from such studies.
Effects of physical exercise therapy on mobility, physical functioning, physical activity and quality of life in community-dwelling older adults with impaired mobility, physical disability and/or multi-morbidity: A meta-analysis
Authors: N.M. de Vries, C.D. van Ravensberg, J.S.M. Hobbelen, M.G.M. Olde Rikkert, J.B. Staal, M.W.G. Nijhuis-van der Sanden
Journal: Ageing Research Reviews (2011)
2,4-DINITROPHENYL RECEPTORS ON MOUSE THYMUS AND SPLEEN CELLS
Authors: David A. Lawrence, Hans L. Spiegelberg, William O. Weigle
Journal: The Journal of Experimental Medicine (1973)

A higher percentage of specific antigen-binding cells can be detected not only in normal CBA/J mouse spleen cell preparations (0.99%), but also in the normal thymus cell preparations (0.15%) with the use of [(125)I]2,4-dinitrophenyl-human IgG (DNP-HGG) as compared with most other antigens employed under similar conditions. The receptors on these cells are mainly specific for the DNP group as shown by the inhibition studies with DNP-lysine and the other DNP conjugates. In addition, it was shown by the inhibition studies with DNP-lysine that the thymus cells seem to have a lower avidity for DNP than the spleen cells. Preincubation of cell suspensions with antisera to immunoglobulins showed that the DNP-HGG antigen-binding cells in the thymus are inhibited predominantly with anti-micro-chain serum and the spleen cells with both anti-micro-chain and anti-gamma-chain sera; both cell populations were also significantly inhibited with the antisera to kappa-chains and Fab fragments. These data indicate that the nature of the receptor on the T cell differs from that on the majority of spleen cells.
Cryotherapy is preferable to ablative CO<sub>2</sub>laser for the treatment of isolated actinic keratoses of the face and scalp: a randomized clinical trial
Authors: C. Zane, E. Facchinetti, M.T. Rossi, C. Specchia, B. Ortel, P. Calzavara-Pinton
Journal: British Journal of Dermatology (2014)

Actinic keratosis (AK) may progress to squamous cell carcinoma. In the case of normal or mildly photodamaged skin, lesion‐directed treatments are considered valuable options despite poor published evidence of their therapeutic activity. The aim of this single‐centre, open‐label, prospective, nonsponsored, randomized, controlled clinical trial was to compare CO2 laser ablation with cryotherapy in the treatment of isolated AKs of the face and scalp. Patients with isolated (≤ 4) AKs of the face and scalp were randomized to receive CO2 laser ablation or cryotherapy. After 90 days, the overall complete remission (CR) rates of patients and lesions were assessed and correlated with thickness grade. Two hundred patients with a total number of 543 AKs were enrolled. The CR rates of lesions after 3 months were 78·2% with cryotherapy and 72·4% with CO2 laser ablation. Thicker lesions were significantly more responsive to cryotherapy (P =0·034). Seventy‐three patients (71·6%) had CR of all lesions 3 months after cryotherapy and 64 (65·3%) after laser ablation. At 12 months after treatment the number of patients with CR was reduced to 53 with cryotherapy and 14 with laser ablation. The rate of patients and lesions with CR is similar after 3 months, but more patients remain in stable remission for 12 months after cryotherapy. Cryotherapy is more effective for thick lesions. The cosmetic outcome was good or excellent in almost all patients.
Reduced sinus arrhythmia in diabetic autonomic neuropathy: diagnostic value of an age-related normal range.
Authors: S A Smith
Journal: BMJ (1982)

A study was carried out to establish a normal range for use in a deep breathing test of cardiac vagal integrity in diabetes mellitus. The change in heart rate resulting from taking a deep breath was recorded in 174 healthy subjects aged 16-89 years. Results were expressed as the ratio of the longest R-R interval during expiration to the shortest R-R interval during inspiration. This ratio declined appreciably with age (p less than 0.001) but was not significantly related to resting heart rate. An age-related normal range was constructed and its diagnostic value investigated in 134 diabetics (aged 15-70 years) with various degrees of neuropathy. The sensitivity for indicating autonomic dysfunction was high: six false-negative and one false-positive result were obtained. Measurement of this age-dependent ratio, which may be made with any electrocardiographic apparatus, provides a simple, accurate diagnostic screen for autonomic neuropathy in the clinic.
Acrokeratosis paraneoplastica of Bazex presenting with carpal tunnel syndrome
Authors: B.L. Poskitt, M.B. Duffill
Journal: British Journal of Dermatology (1992)

Journal Article Acrokeratosis paraneoplastica of Bazex presenting with carpal tunnel syndrome Get access B.L. Poskitt, B.L. Poskitt Department of Dermatology, Waikato Hospital, Private Bag, Hamilton, New Zealand Search for other works by this author on: Oxford Academic Google Scholar M.B. Duffill M.B. Duffill Department of Dermatology, Waikato Hospital, Private Bag, Hamilton, New Zealand Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 5, 1 November 1992, Pages 544–545, https://doi.org/10.1111/j.1365-2133.1992.tb14860.x Published: 01 November 1992
Human Kidney Cell Reprogramming
Authors: Adam C. O’Neill, Sharon D. Ricardo
Journal: Journal of the American Society of Nephrology (2013)

The ability to reprogram fully differentiated cells into a pluripotent embryonic state, termed induced pluripotent stem cells (iPSCs), has been met with great excitement. iPSC technology has advanced the fundamental study of disease modeling with the potential for cell-replacement therapy, especially in the neuronal and cardiac fields. However, renal medicine as of yet has not benefited from similar advancements. This review summarizes the unique characteristics of iPSCs and their potential applications for modeling kidney disease. Pioneering such endeavors could yield constructs that recapitulate disease phenotypes, open avenues for more targeted drug development, and potentially serve as replenishable sources for replacement of kidney cells in the setting of human disease.
Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus.
Authors: V P Argaet, C W Schmidt, S R Burrows, S L Silins, M G Kurilla, D L Doolan, A Suhrbier, D J Moss, E Kieff, T B Sculley, I S Misko
Journal: The Journal of Experimental Medicine (1994)

To examine T cell receptor (TCR) diversity involved in the memory response to a persistent human pathogen, we determined nucleotide sequences encoding TCR-alpha and -beta chains from HLA-B8-restricted, CD8+ cytotoxic T cell clones specific for an immunodominant epitope (FLRGRAYGL) in Epstein-Barr virus (EBV) nuclear antigen 3. Herein, we show that identical TCR protein sequences are used by clones from each of four healthy unrelated virus carriers; a clone from a fifth varied conservatively at only two residues. This dominant selection of alpha and beta chain rearrangements suggest that a persistent viral infection can select for a highly focused memory response and indicates a strong bias in gene segment usage and recombination. A novel double-step semiquantitative polymerase chain reaction (PCR) procedure and direct sequencing of amplified TCR cDNA from fresh lymphocytes derived from three HLA-B8 individuals detected transcripts specific for the conserved beta chain in an EBV-seropositive donor but not in two seronegative donors. This report describes an unprecedented degree of conservation in TCR selected in response to a natural persistent infection.
Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome
Authors: Mizuki Nishino, Anita Giobbie-Hurder, Nikhil H Ramaiya, F Stephen Hodi
Journal: Journal for ImmunoTherapy of Cancer (2014)

Investigate the tumor diameter and density changes in advanced melanoma patients treated with ipilimumab plus bevacizumab, compare response rates based on different response criteria, and study association between these measures and survival.
Toll-like receptor–independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation
Authors: Yasutaka Okabe, Kohki Kawane, Shizuo Akira, Tadatsugu Taniguchi, Shigekazu Nagata
Journal: The Journal of Experimental Medicine (2005)

Deoxyribonuclease (DNase) II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. DNase II–deficient mouse embryos accumulate undigested DNA in macrophages, and die in feto because of the activation of the interferon β (IFNβ) gene. Here, we found that the F4/80-positive macrophages in DNase II−/− fetal liver specifically produce a set of cytokines such as IFNβ, TNFα, and CXCL10. Whereas, IFN-inducible genes (2′5′-oligo(A) synthetase, IRF7, and ISG15) were expressed not only in macrophages but also in other F4/80-negative cells. When DNase II−/− macrophages or embryonal fibroblasts engulfed apoptotic cells, they expressed the IFNβ and CXCL10 genes. The ablation of Toll-like receptor (TLR) 3 and 9, or their adaptor molecules (MyD88 and TRIF), had no effect on the lethality of the DNase II−/− mice. These results indicate that there is a TLR-independent sensing mechanism to activate the innate immunity for the endogenous DNA escaping lysosomal degradation.
TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice
Authors: Hua Wang, Scot A. Marsters, Thad Baker, Betty Chan, Wyne P. Lee, Ling Fu, Daniel Tumas, Minhong Yan, Vishva M. Dixit, Avi Ashkenazi, Iqbal S. Grewal
Journal: Nature Immunology (2001)
Characterization of S628N
Authors: Marina Vita, Julie C. Tisserand, Isaure Chauvot de Beauchêne, Nicolas Panel, Luba Tchertanov, Julie Agopian, Lenaïg Mescam-Mancini, Bernard Fouet, Béatrice Fournier, Patrice Dubreuil, François Bertucci, Paulo De Sepulveda
Journal: JAMA Dermatology (2014)

IMPORTANCE The KIT receptor is mutated in approximately 15%of acral, mucosal, and chronic, sun-damaged melanomas. The status of KIT mutations is of interest because they usually are mutually exclusive with N-RAS and B-RAF mutations and because of the availability of KIT kinase inhibitors in the clinic. Some recurrent KIT mutations are well characterized; others are poorly described.OBSERVATIONS We describe a novel KIT mutation in a patient with metastatic melanoma. The mutation, located in exon 13, resulted in S628N substitution in the KIT receptor. Using all-atom molecular dynamics simulations, biochemical assays, and cell-based assays, we showed that the mutation is a bona fide gain-of-function oncogenic mutation. Furthermore,we evaluated the sensitivity of the mutant to imatinib and dasatinib.CONCLUSIONS AND RELEVANCE We report a novel KIT gain-of-function mutation with S628N substitution (exon 13) and show that it is sensitive to imatinib in vitro. Therefore, patients with this mutation may be eligible for KIT kinase inhibitor–based therapy. Further studies are needed to evaluate the clinical benefit of such therapy.
Physical Activity, Weight Control, and Breast Cancer Risk and Survival: Clinical Trial Rationale and Design Considerations
Authors: Rachel Ballard-Barbash, Sally Hunsberger, Marianne H. Alciati, Steven N. Blair, Pamela J. Goodwin, Anne McTiernan, Rena Wing, Arthur Schatzkin
Journal: JNCI Journal of the National Cancer Institute (2009)

Substantial observational epidemiological evidence exists that physical activity and weight control are associated with decreased risk of postmenopausal breast cancer. Uncertainty remains regarding several aspects of these associations, including the effect of possible confounding factors on these associations. We present the rationale and design for two randomized controlled trials that can help resolve this uncertainty. In a 5-year prevention trial conducted among women at high risk of breast cancer, the primary endpoint would be breast cancer incidence. For a comparable survivorship trial, the primary endpoint would be the disease-free interval and secondary endpoints would be breast cancer recurrence–free interval, second primary breast cancer, and total invasive plus in situ breast cancer. A set of inclusion and exclusion criteria is proposed for both trials. Intervention goals are the same for both trials. Goals for the weight control intervention would be, for women whose body mass index (BMI) is greater than 25 kg/m 2 , to lose 10% of body weight and, for women whose BMI is less than or equal to 25 kg/m 2 , to avoid weight gain. The goal for the physical activity intervention would be to achieve and maintain regular participation in a moderate-intensity physical activity program for a total of 150–225 minutes over at least 5 days per week. Sample size calculations are based on alternative assumptions about hazard ratio, adherence, follow-up duration, and power and are presented for the primary prevention and survivorship trials. Although both studies could enhance our understanding of breast cancer etiology and benefit public health, practical considerations, including smaller sample size, ease of recruitment, and reduced likelihood of early termination, favor the survivorship trial at this time.
A Randomised Controlled Trial of Ion-Exchange Water Softeners for the Treatment of Eczema in Children
Authors: Kim S. Thomas, Tara Dean, Caroline O'Leary, Tracey H. Sach, Karin Koller, Anthony Frost, Hywel C. Williams
Journal: PLoS Medicine (2011)

Background Epidemiological studies and anecdotal reports suggest a possible link between household use of hard water and atopic eczema. We sought to test whether installation of an ion-exchange water softener in the home can improve eczema in children. Methods and Findings This was an observer-blind randomised trial involving 336 children (aged 6 months to 16 years) with moderate/severe atopic eczema. All lived in hard water areas (≥200 mg/l calcium carbonate). Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. The primary outcome was change in eczema severity (Six Area Six Sign Atopic Dermatitis Score, SASSAD) at 12 weeks, measured by research nurses who were blinded to treatment allocation. Analysis was based on the intent-to-treat population. Eczema severity improved for both groups during the trial. The mean change in SASSAD at 12 weeks was −5.0 (20% improvement) for the water softener group and −5.7 (22% improvement) for the usual care group (mean difference 0.66, 95% confidence interval −1.37 to 2.69, p = 0.53). No between-group differences were noted in the use of topical corticosteroids or calcineurin inhibitors. Conclusions Water softeners provided no additional benefit to usual care in this study population. Small but statistically significant differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias, since participants were aware of their treatment allocation. A detailed report for this trial is also available at http://www.hta.ac.uk. Trial registration Current Controlled Trials ISRCTN71423189 Please see later in the article for the Editors' Summary