tbuckley/cabot-search huggingface dataset:
A simulation study of the effects of torso inhomogeneities on electrocardiographic potentials, using realistic heart and torso models.
Authors: R M Gulrajani, G E Mailloux
Journal: Circulation Research (1983)

The effects of torso inhomogeneities on electrocardiographic potentials were investigated via computer stimulation, using a 23-dipole heart model placed within a realistically shaped human torso model. The transfer coefficients relating the individual dipoles to the torso surface potentials, as well as the body surface potential maps, the vectorcardiogram, and the 12-lead electrocardiogram resulting due to normal activation of the heart model, were calculated for each of the following torso conditions: homogeneous, homogeneous + skeletal muscle layer, homogeneous + muscle layer + lungs, and homogeneous + muscle layer + lungs + intraventricular blood masses. The effects of each inhomogeneity were deduced by comparing results before and after its inclusion. For individual dipole transfer coefficients we confirm the validity of the "Brody effect," whereby the high conductivity blood masses augment radially oriented dipoles and diminish tangentially oriented ones. With regard to the vectorcardiogram , the electrocardiogram, and the body surface potential maps, the major qualitative effects were an augmentation of the head-to-foot component of the vectorcardiogram due to the lungs, and a smoothening of notches in the electrocardiogram (temporal filtering) and of isopotential contours in the body surface potential maps (spatial filtering) with a consequent loss of information, due to the blood masses, muscle layer, and, to a lesser extent, the lungs. Besides the above qualitative effects of the inhomogeneities, there were also large quantitative effects on the surface potentials, namely, magnitude increases due to the blood masses and magnitude decreases due to the muscle layer, that--if unaccounted for--could compromise the inverse solution of these potentials for the cardiac dipole sources.
Government should not take "big stick" to NHS after Mid Staffs report, says think tank
Authors: A. O'Dowd
Journal: BMJ (2013)

<h3>Abstract</h3> There is widespread interest in the capacity for SARS-CoV-2 evolution in the face of selective pressures from host immunity, either naturally acquired post-exposure or from vaccine acquired immunity. Allied to this is the potential for long perm persistent infections within immune compromised individuals to allow a broader range of viral evolution in the face of sub-optimal immune driven selective pressure. Here we report on an immunocompromised individual who is hypogammaglobulinaemic and was persistently infected with SARS-CoV-2 for over 290 days, the longest persistent infection recorded in the literature to date. During this time, nine samples of viral nucleic acid were obtained and analysed by next-generation sequencing. Initially only a single mutation (L179I) was detected in the spike protein relative to the prototypic SARS-CoV-2 Wuhan-Hu-1 isolate, with no further changes identified at day 58. However, by day 155 the spike protein had acquired a further four amino acid changes, namely S255F, S477N, H655Y and D1620A and a two amino acid deletion (ΔH69/ΔV70). Infectious virus was cultured from a nasopharyngeal sample taken on day 155 and next-generation sequencing confirmed that the mutations in the virus mirrored those identified by sequencing of the corresponding swab sample. The isolated virus was susceptible to remdesivir <i>in vitro</i>, however a 17-day course of remdesivir started on day 213 had no effect on the viral RT-PCR cycle threshold (C<sub>t</sub>) value. On day 265 the patient was treated with the combination of casirivimab and imdevimab. The patient experienced progressive resolution of all symptoms over the next 8 weeks and by day 311 the virus was no longer detectable by RT-PCR. The ΔH69/ΔV70 deletion in the N-terminus of the spike protein which arose in our patient is also present in the B.1.1.7 variant of concern and has been associated with viral escape mutagenesis after treatment of another immunocompromised patient with convalescent plasma. Our data confirms the significance of this deletion in immunocompromised patients but illustrates it can arise independently of passive antibody transfer, suggesting the deletion may be an enabling mutation that compensates for distant changes in the spike protein that arise under selective pressure.
Drug Resistance-Reversal Strategies: Comparison of Experimental Data With Model Predictions
Authors: Doris Slate, Seth Michelson
Journal: JNCI Journal of the National Cancer Institute (1991)

We previously developed a mathematical model to describe the emergence and dynamic growth of a drug-resistant subpopulation in a tumor. In the present study, our objective was to test the model's ability to mimic two strategies for reversal of drug resistance. We present data from one in vitro cell proliferation assay with drug resistant LS174T human colon carcinoma variants and one in vivo assay of survival after treatment of female (C57BL/6×DBA/2)F 1 mice inoculated with doxorubicin–resistant P388/ADR leukemia cells. The in vitro assay examined the effects of inhibiting the biosynthesis of glutathione in cells resistant to alkylating agents or cisplatin. The in vivo assay compared the effects on cell survival of low-level continuous infusion versus high-intensity bolus dosing, with or without coad-ministration of the drug efflux pump blocker verapamil. Results in vitro and in vivo were comparable for qualitative accuracy and predictability to results with the model. Both the in vitro study and the model showed that, for resistant cells with high levels of glutathione, short-term cell survival was dose dependent and that even high doses of drug did not eliminate all of these cells. Addition of an inhibitor of glutathione biosynthesis did, however, augment elimination of the resistant cells. Resistant cells with low levels of glutathione could be eliminated with high drug doses or coadministration of drug and a glutathione synthesis in-hibitor. In vivo, coadministration of doxorubicin with verapamil increased animal survival when either continuous infusion or bolus dosing regimens were used. The effectiveness of the blocker is crucial; when a partially (50%) effective blocker is used, continuous infusion achieves better elimination of resistant cells, but a completely (100%) effective blocker is efficacious in both dosing scenarios. Careful interpretation of these findings is necessary because the pharmacokinetics of drug in the small populations of cells in the model are not easily extrapolated to those in large tumors. This model may be useful in determining resistance mechanisms, their levels of effectiveness, and concentrations of compounds required at target sites to overcome them. [J Natl Cancer Inst 83:1574–1580, 1991]
REGULATION OF IMMUNOGLOBULIN SYNTHESIS BY DEXTRAN
Authors: Jack R. Battisto, Frances Pappas
Journal: The Journal of Experimental Medicine (1973)

Dextran, of the variety commonly used as plasma expander, markedly altered antibody synthesis to an unrelated antigenic stimulus, SRBC, in two animal species, guinea pig and mouse. The time at which dextran was administered relative to antigen was found to be most critical for increasing or decreasing the number of IgM and IgG PFC. Furthermore, these times differed for the two species studied. Typically, when given to guinea pigs 6 h before SRBC, dextran caused a 20-fold rise in IgM-producing cells but had little effect upon IgG synthesis. However, if dextran preceded antigen by 24 h the same magnitude of increase was seen in IgG-forming cells while a decrease in IgM-producing cells occurred. In mice, a short 2 h interval between dextran and antigen favored cells synthesizing IgG and not those producing IgM. A longer 6 to 24 h lapse between dextran and antigen resulted again in an inverted pattern, i.e., an increase in IgM and a decrease in IgG-producing cells. In both species, if dextran was given 48 h before antigen, synthesis of IgG markedly decreased. At the cellular level dextran activated those B cells already in the vascular compartment. In stimulating the IgM response to SRBC, dextran appears either to substitute for T cells or to amplify the effects of that small number of T cells still present in bone marrow preparations. Dextran-altered mouse B cells synthesized SRBC-specific IgG in the presence of normal T cells at an earlier time than did normal B and T cells. However, dextran was unable to cause blastogenesis in vitro of guinea pig lymph node cells or mouse B, T, and spleen cells. The data suggest at least two effects that T cells exert upon B cells. One is to stimulate more B cells to produce IgM, a function accomplished by endotoxins, PWM, PPD, and the simple polysaccharide dextran. The other is to trigger shifts in synthesis of immunoglobulins M and G. Our observations are compatible with the view that a single cell is capable of synthesizing both of these immunoglobulins and that the stimulating factor for one may cause cessation of the other.
MMP expression and abnormal lung permeability are important determinants of outcome in IPF
Authors: S. McKeown, A. G. Richter, C. O'Kane, D. F. McAuley, D. R. Thickett
Journal: European Respiratory Journal (2008)

Matrix metalloproteinases (MMPs) degrade all of the extracellular matrix components of the intersititium and may play a role in abnormal alveolar permeability, which is a feature of idiopathic pulmonary fibrosis (IPF). The aims of the present study were to evaluate MMP protein levels in patients with IPF and determine any relationship to treatment and markers of permeability. In total, 20 patients with IPF and eight normal controls underwent bronchoalveolar lavage. MMP, tissue inhibitor of metalloproteinase, and vascular endothelial growth factor (VEGF) levels were related to clinical outcome and protein permeability index. MMP-3, -7, -8 and -9 were elevated in IPF lavage fluid and levels remained high despite treatment. Levels of MMP-3, -7, -8 and -9, VEGF and protein permeability index were higher in those who died early during follow-up. VEGF, and MMP-8 and -9 levels were higher in those with a rapidly declining lung function over 1 yr. Levels of MMP-3, -7, -8 and -9 correlated with an increased permeability index. Matrix metalloproteinase levels were elevated in idiopathic pulmonary fibrosis patients and were not modulated by current standard treatment. Matrix metalloproteinase production through an interaction with the known vascular permogen, vascular endothelial growth factor, was potentially associated with abnormal capillary permeability and may have potentiated the neo-angiogenesis seen in idiopathic pulmonary fibrosis. The changes were greatest in those who died or progressed during follow-up, suggesting that drugs targeting vascular endothelial growth factor or matrix metalloproteinase activity warrant assessment as novel therapy for idiopathic pulmonary fibrosis.
729-4 Left Ventricular Hypertrophy and the Deletion-Insertion Polymorphism of the Angiotensin Converting Enzyme Gene
Authors: Daniel Levy, Klaus Lindpaintner, Martin G. Larson, Vasan S. Ramachandran, Richard H. Myers, Marc A. Pfeffer, Jose M. Ordovas, Ernst J. Schaefer, Peter WF. Wilson
Journal: Journal of the American College of Cardiology (1995)
A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer
Authors: E. Van Cutsem, C. Pozzo, H. Starkhammar, L. Dirix, E. Terzoli, F. Cognetti, Y. Humblet, C. Garufi, L. Filez, G. Gruia, C. Cote, C. Barone
Journal: Annals of Oncology (1998)
Organizing knowledge to enable personalization of medicine in cancer
Authors: Benjamin M Good, Benjamin J Ainscough, Josh F McMichael, Andrew I Su, Obi L Griffith
Journal: Genome biology (2014)

Interpretation of the clinical significance of genomic alterations remains the most severe bottleneck preventing the realization of personalized medicine in cancer. We propose a knowledge commons to facilitate collaborative contributions and open discussion of clinical decision-making based on genomic events in cancer.
Pharmacologically Preconditioned Skeletal Myoblasts Are Resistant to Oxidative Stress and Promote Angiomyogenesis via Release of Paracrine Factors in the Infarcted Heart
Authors: Muhammad Idris Niagara, Husnain Kh. Haider, Shujia Jiang, Muhammad Ashraf
Journal: Circulation Research (2007)

Strategies to enhance skeletal myoblast (SkM) survival after transplantation in the ischemic heart have achieved little success. We posit that preconditioned (PC) SkMs show improved survival and promote repair of the infarcted myocardium via paracrine signaling after transplantation. SkMs from male Fischer-344 rats (rSkMs) were PC for 30 minutes with 200 μmol/L diazoxide. Treatment of PC rSkMs with 100 μmol/L H 2 O 2 for 2 hours resulted in significantly reduced cell injury, as shown by lactate dehydrogenase–release assay, and prevented apoptosis, as demonstrated by cytochrome c translocation, TUNEL, annexin V staining, and preservation of mitochondrial membrane potential. PC rSkMs expressed elevated phospho-Akt (1.85-fold), basic fibroblast growth factor (1.44-fold), hepatocyte growth factor (2.26-fold), and cyclooxygenase-2 (1.33-fold) as compared with non-PC rSkMs. For in vivo studies, female Fischer-344 rats after permanent coronary artery ligation were grouped (n=12/group) to receive 80 μL of basal medium without rSkMs (group 1) or containing 1.5×10 6 non-PC (group 2) or PC (group 3) rSkMs. Real-time PCR for sry gene 4 days after transplantation (n=4/group) showed 1.93-fold higher survival of rSkMs in group 3 as compared with group 2. Four weeks later, echocardiography revealed improved indices of left ventricular function, including ejection fraction and fractional shortening in group 3 ( P &lt;0.02) as compared with groups 1 and 2. Blood vessel count per surface area (at ×400 magnification) was highest in scar and periscar areas in group 3 as compared with the other groups ( P &lt;0.05). We conclude that activation of signaling pathways of preconditioning in SkMs promoted their survival by release of paracrine factors to promote angiomyogenesis in the infarcted heart. Transplantation of PC SkMs for heart cell therapy is an innovative approach in the clinical perspective.
A spare or an individual? Cloning and the implications of monozygotic twinning
Authors: E. Bryan
Journal: Human Reproduction Update (1998)

The creation of Dolly, the cloned sheep, raises the scenario of cloning in humans. Neither the case for, nor against, the ethics of cloning in humans is discussed in this paper. Instead, it considers the neglected issue of the likely happiness or otherwise of the resulting children if they are born as monozygotic twins or triplets. The advantages and disadvantages of twinship are discussed in detail, and it is concluded that recognized that recognized medical risks, and incompletely understood psychological effects, should be given serious consideration.
Spontaneous autoimmunization to GIX cell surface antigen in hybrid mice.
Authors: Y Obata, E Stockert, E A Boyse, J S Tung, G W Litman
Journal: The Journal of Experimental Medicine (1976)

The GIX antigen expressed on the thymocytes of GIX+ mice is a type-specific constituent of glycoprotein gp70, which forms the major envelope component of murine leukemia virus. In the prototype GIX+ mouse strain 129, this glycoprotein is a Mendelian character expressed independently of virus production. In the intact thymocyte plasma membrane, part of this glycoprotein, bearing group-specific (gs) antigen, is inaccessible to antibody. The moiety bearing the type-specific GIX determinant is accessible to GIX antibody, which may be an important factor in determining the consequences of autoimmune responses involving GIX. Previously, all attempts to induce GIX antibody in mice had failed. We now find that the hybrid mouse (B6-GIX+ X 129) spontaneously produces substantial amounts of GIX antibody, presumably of the IgM class appearing as early as 2 mo of age. The specificity of the GIX natural mouse antibody is the same as that recognized by the conventional GIX typing serum produced in rats ("anti-NTD"). As neither parent strain produces appreciable GIX antibody, we surmise that this autoimmune response requires two dominant genes, each parent contributing a high-response allele to the hybrid. These can be envisaged as two immune response loci, controlling different immunocompetent cells which must cooperate to produce GIX antibody. Production of GIX antibody by the hybrids increases progressively with age. This is accompanied by decreased expression of GIX antigen on their thymocytes. We attribute this to antigenic modulation. Antibody to gs antigen of gp70 is also found in autoimmune (B6-GIX+ X 129) hybrids but not in either parent strain. We are investigating evidence of a pathological autoimmune syndrome in these hybrids. The special interest of this syndrome is that it presumably signifies the consequences of autoimmunization to a single C-type virus component, expressed without significant virus production, in a mouse with no evident genetic predisposition to such disease in the absence of that antigen.
New anticoagulants should be considered for atrial fibrillation, says NICE
Authors: I. Torjesen
Journal: BMJ (2014)

GPs should no longer automatically prescribe warfarin as the first line treatment for atrial fibrillation but weight up its risks and benefits against those of the newer anticoagulants, the UK National Institute for Health and Care Excellence (NICE) has said in a review of its guidance on managing the condition.

NICE’s draft update of its guideline on atrial fibrillation also proposes other wide ranging changes to management, including GP’s routine use of risk calculation scores for stroke and bleeding when assessing and monitoring patients; rate rather than rhythm control as the first line approach; and wider use of non-pharmacological techniques such as electrical cardioversion and ablation.

Patients with atrial fibrillation have a fivefold increased risk of stroke, so preventing stroke is …
The efficacy of nuclease-resistant Chol-siRNA in primary breast tumors following complexation with PLL-PEG(5K)
Authors: Vishakha V. Ambardekar, Rajesh R. Wakaskar, Bhawna Sharma, Joy Bowman, Willy Vayaboury, Rakesh K. Singh, Joseph A. Vetro
Journal: Biomaterials (2013)
155 NON-UNIFORM REGIONAL LIVER REGENERATION AFTER HEPATIC SURGERY WELL CORRELATES WITH COMPUTATIONALLY SIMULATED INCREASES IN BLOOD FLOW AND PRESSURE IN PORTAL BRANCHES
Authors: Y. Iimuro, S. Saito, J. Yamanaka, T. Hirano, N. Kuroda, T. Okada, T. Sugimoto, Y. Asano, N. Uyama, Y. Uda, J. Fujimoto
Journal: Journal of Hepatology (2008)
Perioperative Morbidity of Laparoscopic Cryoablation of Small Renal Masses with Ultrathin Probes: A European Multicentre Experience
Authors: M. Pilar Laguna, Patricia Beemster, Patricia Kumar, H. Christoph Klingler, Stephen Wyler, Chris Anderson, Francis X. Keeley, Alexander Bachmann, Jorge Rioja, Charalampos Mamoulakis, Michael Marberger, Jean J. de la Rosette
Journal: European Urology (2009)
Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma
Authors: Gulab S. Zode, Markus H. Kuehn, Darryl Y. Nishimura, Charles C. Searby, Kabhilan Mohan, Sinisa D. Grozdanic, Kevin Bugge, Michael G. Anderson, Abbot F. Clark, Edwin M. Stone, Val C. Sheffield
Journal: Journal of Clinical Investigation (2015)

An investigation by the University Health Network recently found that portions of the RT-PCR gels shown in Figure 1, B (PGK-1 panel) and C (FGFR1 panel), are duplicated in this publication and in a subsequent publication (1).The samples were labeled differently in the panels, and the marker was shifted in Figure 1B.The corresponding author has indicated that other data from the initial screen of these samples support the conclusions made in the paper; however, the original data for the RT-PCR gels shown in Figure 1 are no longer available.The JCI's policies prohibit data manipulation and data duplication.Therefore, the JCI is retracting this article.No issues have been raised in regard to any of the other data in this manuscript.
Noninvasive differentiation between stable and unstable chronic plaque psoriasis using in vivo reflectance confocal microscopy
Authors: Lisa Hoogedoorn, Esther A.W. Wolberink, Peter C.M. van de Kerkhof, Jan C.M. Hendriks, Marie-Jeanne P. Gerritsen, Piet E.J. van Erp
Journal: Journal of the American Academy of Dermatology (2015)
Superantigenic exotoxin-secreting potential of staphylococci isolated from atopic eczematous skin
Authors: J.P. MCFADDEN, W.C. NOBLE, R.D.R. CAMP
Journal: British Journal of Dermatology (1993)

Although the deleterious effect of Staphylococcus aureus on atopic eczema is well recognized, the mechanism of this effect may be more complex than pyogenic infection alone. We have shown that the majority of S. aureus cultures isolated from atopic eczema produced exotoxins with superantigenic properties, although this was no more frequent than in a control group, and was not restricted to one particular superantigen. However, the widespread nature of staphylococcal infections in atopic eczema indicates that sufficient superantigen may be released to cause T-lymphocyte activation, cytokine release, and mast cell degranulation. These mechanisms could, in part, explain the exacerbations of atopic eczema associated with S. aureus infection.
Mechanism of dopamine inhibition of renal phosphate transport.
Authors: J Isaac, R P Glahn, M M Appel, M Onsgard, T P Dousa, F G Knox
Journal: Journal of the American Society of Nephrology (1992)

Dopamine (DA) is natriuretic and phosphaturic. However, whether the effect of DA on Pi reabsorption is a consequence of its effect on sodium transport is not known. Therefore, this study was performed to determine the effect of DA on the maximal transport of phosphate (TmPi), and upon the capacity of renal proximal brush border membrane (BBM) for (Naextra-vesicular greater than Naintravesicular)-gradient-dependent transport of Pi, as compared with the transport of other solutes. Graded infusions of Pi (0, 1, 2, and 3 mumols/min) were given to thyroparathyroidectomized male Sprague-Dawley rats in the presence of vehicle (0.9% NaCl; N = 5), DA 15 micrograms/kg/min; N = 6), or parathyroid hormone ((PTH); 1 U/kg/min; N = 5). The TmPi for rats infused with DA (3.3 +/- 0.3 mumol/mL) was significantly less than the TmPi for saline control rats (4.4 +/- 0.2 mumol/mL). Rats infused with PTH exhibited the lowest TmPi (1.8 +/- 0.3 mumol/mL). No differences in sodium excretion were observed among any of the groups. Na-dependent Pi transport was studied in BBM vesicles (BBMV) prepared from rats fed a low-phosphate diet for 2 days that were anesthetized, acutely thyroparathyroidectomized, and systemically infused with DA (350 micrograms bolus, plus 35 micrograms/kg/min; N = 8), PTH (33 U/kg bolus, followed by a continuous infusion of 1 U/kg/min; N = 6), or vehicle (1 mL/kg bolus, plus 2 mL/h constant infusion of 0.9% NaCl; N = 8) for 90 min. DA significantly inhibited the Na cotransport of Pi by 22.4 +/- 4.1% (P less than 0.01) as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)