tbuckley/cabot-search huggingface dataset:
Kinetic Studies of Calcium Distribution in Ventricular Muscle of the Dog
Authors: G. A. LANGER, S. D Serena
Journal: Circulation Research (1964)

Five phases (0 to 4) were defined kinetically for calcium in the dog papillary muscle vascularly perfused for five to six hours with perfusate containing 5 m M /liter calcium. The mean rate constant, λ, (min -1 ), approximate calcium concentration (m M /liter muscle water) and suggested origin of each phase are respectively: (0) λ 0 = 3.5, 0.4, vascular; (1) λ 1 = 0.59, 1.8, interstitial; (2) λ 2 = 0.116, 1.7, "specialized" calcium transport system (?sarcoplasmic reticulum); (3) λ 3 = 0.021, 2.0, intracellular; (4) λ approx 0.004, &lt;1.6, intracellular and/or connective tissue. Inotropism, occuring coincidentally with institution of perfusion by solution containing 25% normal sodium concentration, was marked by a mean 60% increase in peak isometric tension and a mean 87% increase in rate of tension development. These inotropic changes stabilized within 10 minutes despite maintenance of low sodium perfusion and regressed within 10 minutes upon return to normal sodium perfusion. There was a mean 0.5 m M /liter change in calcium concentration of the muscle associated with the inotropic changes. This fraction of tissue calcium could be ascribed entirely to kinetically-defined phase 2 and was freely exchangeable. Prolonged (40-minute) low sodium perfusion resulted in no inotropic changes beyond the first 10 minutes but was associated with a continued marked net increase in muscle calcium. This fraction of tissue calcium was irreversibly bound and inexchangeable. It was suggested that this fraction of calcium may be bound as its phosphate salt. The possibility that the Ca ++ content of the "specialized system" represented by phase 2 is controlled by movements of Na + into and out of this system is discussed. Ca ++ movements associated with increased frequency of contraction are also discussed in the context of their possible relation to Na + exchange.
Chromosome Aberrations Acquired In Vitro by Human B-Cell Lines. I. Gains and Losses of Material
Authors: C M Steel, M Shade, M A Woodward
Journal: JNCI Journal of the National Cancer Institute (1980)

Gains and losses of chromosomes or chromosome arms were recorded in 45 of 165 human B-cell lines. Most aberrations were acquired in vitro, and their frequency was related to duration of culture. Gains occurred more frequently than losses and their distribution was nonrandom. Chromosomes most commonly affected were No. 3, 7, 8 (particularly 8q), 9, 12, and 21. Certain differences in the frequency of particular aberrations appeared to be related to the clinical conditions of the patients from whom the lines were derived. The distribution of chromosome gains in this material was correlated with those detected in direct preparations from human tumors.
Human subcutaneous adipose tissue LPIN1 expression in obesity, type 2 diabetes mellitus, and human immunodeficiency virus--associated lipodystrophy syndrome
Authors: Merce Miranda, Matilde R. Chacón, José Gómez, Ana Megía, Victòria Ceperuelo-Mallafré, Sergi Veloso, María Saumoy, Lluís Gallart, Cristóbal Richart, Jose Manuel Fernández-Real, Joan Vendrell
Journal: Metabolism (2007)
Detection of Vein Graft Disease Using High-Resolution Magnetic Resonance Angiography
Authors: Susan E. Langerak, Hubert W. Vliegen, Albert de Roos, Aeilko H. Zwinderman, J. Wouter Jukema, Patrik Kunz, Hildo J. Lamb, Ernst E. van der Wall
Journal: Circulation (2002)

Background — The application of previous magnetic resonance (MR) angiography techniques has enabled noninvasive differentiation between patent and occluded coronary artery bypass grafts. However, the detection of graft stenosis remains difficult. The purpose of our study was to determine the accuracy of high-resolution navigator-gated 3-dimensional (3-D) MR angiography in detecting vein graft disease. Methods and Results — MR angiography was performed in addition to coronary angiography with quantitative coronary analysis in 56 vein grafts from 38 patients (mean age 66.6±9.3 years), who presented with recurrent chest pain after bypass surgery. Eighteen grafts showed a luminal stenosis ≥50%, 11 grafts a stenosis ≥70%, and 6 grafts were occluded. All MR angiograms were evaluated independently by 2 blinded observers, who scored the presence of graft occlusion and graft stenosis ≥50% and ≥70% with a confidence level of 1 to 10. MR image quality was judged as insufficient in 6 grafts and these were excluded. Receiver-operator characteristic analysis revealed an area under the curve of 0.89 and 0.89 for identifying graft occlusion, 0.81 and 0.87 for stenosis ≥50%, and 0.82 and 0.79 for stenosis ≥70% for the 2 observers, respectively. Interobserver agreement in assessing graft occlusion and stenosis ≥50% and ≥70% was 94% (κ=0.74, r =0.81), 72% (κ=0.40, r =0.66), and 82% (κ=0.53, r =0.72), respectively. Conclusions — High-resolution navigator-gated 3-D MR angiography allows not only good differentiation between patent and occluded vein grafts but also the assessment of vein graft disease with a fair diagnostic accuracy. This approach offers perspective as a noninvasive diagnostic tool for patients who present with recurrent chest pain after vein graft surgery.
Clinical Characteristics of Individuals With Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals
Authors: Thomas S. Frank, Amie M. Deffenbaugh, Julia E. Reid, Mark Hulick, Brian E. Ward, Beth Lingenfelter, Kathi L. Gumpper, Thomas Scholl, Sean V. Tavtigian, Dmitry R. Pruss, Gregory C. Critchfield
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the characteristics that correlate best with the presence of mutations in BRCA1 and BRCA2 in individuals tested in a clinical setting. PATIENTS AND METHODS: The results of 10,000 consecutive gene sequence analyses performed to identify mutations anywhere in the BRCA1 and BRCA2 genes (7,461 analyses) or for three specific Ashkenazi Jewish founder mutations (2,539 analyses) were correlated with personal and family history of cancer, ancestry, invasive versus noninvasive breast neoplasia, and sex. RESULTS: Mutations were identified in 1,720 (17.2%) of the 10,000 individuals tested, including 968 (20%) of 4,843 women with breast cancer and 281 (34%) of 824 with ovarian cancer, and the prevalence of mutations was correlated with specific features of the personal and family histories of the individuals tested. Mutations were as prevalent in high-risk women of African (25 [19%] of 133) and other non-Ashkenazi ancestries as those of European ancestry (712 [16%] of 4379) and were significantly less prevalent in women diagnosed before 50 years of age with ductal carcinoma in situ than with invasive breast cancer (13% v 24%, P = .0007). Of the 74 mutations identified in individuals of Ashkenazi ancestry through full sequence analysis of both BRCA1 and BRCA2, 16 (21.6%) were nonfounder mutations, including seven in BRCA1 and nine in BRCA2. Twenty-one (28%) of 76 men with breast cancer carried mutations, of which more than one third occurred in BRCA1. CONCLUSION: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.
Safety and Efficacy of Low Molecular Weight Heparins for Hemodialysis in Patients with End-Stage Renal Failure
Authors: Wendy Lim, Deborah J. Cook, Mark A. Crowther
Journal: Journal of the American Society of Nephrology (2004)

Low molecular weight heparins (LWMH) are the preferred initial treatment for many thromboembolic disorders but are renally excreted and relatively contraindicated in patients with renal failure because of concerns of increased bleeding risks. The purpose of this study was to evaluate the safety and efficacy of LMWH compared with unfractionated heparin (UFH) for preventing thrombosis of the extracorporeal dialysis circuit. Studies were identified with the use of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and FirstSearch; reference lists were reviewed; and pharmaceutical companies were contacted. Randomized, controlled trials that compared an LMWH with another anticoagulant during hemodialysis in patients with ESRD and reported at least one of bleeding, extracorporeal circuit thrombosis, or anti-Xa levels were chosen. Two reviewers independently extracted data on methodologic quality, study design, clinical outcomes, and anti-Xa levels. Seventeen trials were included in this systematic review, 11 of which were included in the meta-analysis. It was found that LMWH did not significantly affect the number of bleeding events (relative risk, 0.96; 95% confidence interval [CI], 0.27 to 3.43), bleeding assessed by vascular access compression time (weighted mean difference, −0.87; 95% CI, −2.75 to 1.02), or extracorporeal circuit thrombosis (relative risk, 1.15; 95% CI, 0.70 to 1.91) as compared with UFH. LMWH seem to be as safe as UFH in terms of bleeding complications and as effective as UFH in preventing extracorporeal circuit thrombosis. However, inferences from these trials assessing anticoagulation for patients who undergo hemodialysis will continue to be weak until larger, more rigorous randomized trials are conducted.
Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1
Authors: Praveena S. Thiagarajan, Valentin P. Yakubenko, Deena H. Elsori, Satya P. Yadav, Belinda Willard, Carmela D. Tan, E. René Rodriguez, Maria Febbraio, Martha K. Cathcart
Journal: Cardiovascular Research (2013)

Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O2−) inducing low-density lipoprotein (LDL) oxidation leading to their unregulated uptake of oxidized LDL and foam cell formation. We recently discovered that zymosan potently activates monocyte NADPH oxidase via the non-toll pattern recognition receptor (PRR), Dectin-1. Other PRRs bind endogenous human ligands, yet no such ligands have been identified for Dectin-1. Our hypothesis was that inflammation generates endogenous ligands for Dectin-1 that activate O2− production and thereby contributes to atherogenesis. Human: anti-zymosan antibodies were used to identify similar, cross-reactive epitopes in human atherosclerotic tissue extracts. Immunoblot analysis revealed consistent antibody reactive protein bands on one- and two-dimensional gel electrophoreses. Vimentin was identified by mass spectrometry in the immunoreactive bands across different tissue samples. Direct binding of vimentin to Dectin-1 was observed using BIACORE. Further data revealed that vimentin induces O2− production by human monocytes. Analysis of human atherosclerotic lesions revealed that vimentin was detected extracellularly in the necrotic core and in areas of active inflammation. Vimentin also co-localized with Dectin-1 in macrophage-rich regions where O2− is produced. We conclude that vimentin is an endogenous, activating ligand for Dectin-1. Its presence in areas of artery wall inflammation and O2− production suggests that vimentin activates Dectin-1 and contributes to the oxidation of lipids and cholesterol accumulation in atherosclerosis.
Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers
Authors: D Morrison, RM Strieter, SC Donnelly, MD Burdick, SL Kunkel, W MacNee
Journal: European Respiratory Journal (1998)

Polymorphonuclear neutrophils (PMN) have been implicated in the pathogenesis of emphysema. The chemokines interleukin-8(IL-8), growth-related oncogene (GRO-alpha) and extractable nuclear antigen (ENA)-78 may be involved in the increased numbers of PMN in smokers' airspaces. The levels of these cytokines in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage leukocyte conditioned medium (LCM), along with BALF PMN numbers in 12 smokers who abstained for 12 h (chronic smoking) or continued to smoke until I h before study (acute smoking) and seven nonsmokers were compared. Neutrophils in BALF increased in acute (1.96+/-0.53%, 0.99+/-0.32x10(6) cells) compared with chronic smokers (0.59+/-0.25%, 0.61+/-0.24x10(6) cells, p<0.05 nonsmokers) and nonsmokers (0.79+/-0.29%, 0.05+/-0.01x 10(6) cells, p<0.05). There were no differences in IL-8 or GRO-alpha in BALF between smokers and nonsmokers. ENA-78 levels were lower in smokers (p=0.006). There was no difference in IL-8, GRO-alpha or ENA-78 in LCM from unstimulated cells in smokers versus nonsmokers. After stimulation with lipopolysaccharide (LPS) 10 ng mL(-1), IL-8 release in acute smokers (p=0.04) and GRO-alpha release in smokers (p=0.009) were significantly higher than in nonsmokers. Following stimulation with LPS 100 ng.mL(-1), GRO-alpha release was higher in smokers (p=0.03) and increased further in acute smokers (p=0.02 versus nonsmokers, p=0.04 versus chronic smokers) and ENA-78 release increased in smokers (p=0.02 versus non-smokers). In conclusion, influx of polymorphonuclear neutrophils into smokers' airspaces is an acute phenomenon and neutrophil chemokine release from mixed bronchoalveolar lavage leukocytes is influenced by cigarette smoking and endotoxins.
CD8+ T cell stimulation with pegylated recombinant human IL-10 in the patient with advanced solid tumors - a Phase I study
Authors: Aung Naing, Jeffrey R Infante, Kyriakos P Papadopoulos, Karen A Autio, Deborah J Wong, Gerald S Falchook, Manish R Patel, Shubham Pant, Melinda Whiteside, Johanna Bendell, Todd M Bauer, Filip Janku, Milind Javle, Rivka Colen, Nizar Tannir, Martin Oft
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In preclinical studies, PEGylated IL-10 (PEG-IL-10) but not non-PEG IL-10 induces tumor rejection by the directly activating and increasing the proliferation of tumor specific CD8 T cells within the tumor. PEG-IL-10 activates STAT3 and STAT1 in tumor infiltrating CD8 T cells. PEG-
High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias
Authors: Joseph Y. Shin, Wenhuo Hu, Mayumi Naramura, Christopher Y. Park
Journal: The Journal of Experimental Medicine (2014)

Hematopoietic stem cells (HSCs) are heterogeneous with respect to their self-renewal, lineage, and reconstitution potentials. Although c-Kit is required for HSC function, gain and loss-of-function c-Kit mutants suggest that even small changes in c-Kit signaling profoundly affect HSC function. Herein, we demonstrate that even the most rigorously defined HSCs can be separated into functionally distinct subsets based on c-Kit activity. Functional and transcriptome studies show HSCs with low levels of surface c-Kit expression (c-Kit(lo)) and signaling exhibit enhanced self-renewal and long-term reconstitution potential compared with c-Kit(hi) HSCs. Furthermore, c-Kit(lo) and c-Kit(hi) HSCs are hierarchically organized, with c-Kit(hi) HSCs arising from c-Kit(lo) HSCs. In addition, whereas c-Kit(hi) HSCs give rise to long-term lymphomyeloid grafts, they exhibit an intrinsic megakaryocytic lineage bias. These functional differences between c-Kit(lo) and c-Kit(hi) HSCs persist even under conditions of stress hematopoiesis induced by 5-fluorouracil. Finally, our studies show that the transition from c-Kit(lo) to c-Kit(hi) HSC is negatively regulated by c-Cbl. Overall, these studies demonstrate that HSCs exhibiting enhanced self-renewal potential can be isolated based on c-Kit expression during both steady state and stress hematopoiesis. Moreover, they provide further evidence that the intrinsic functional heterogeneity previously described for HSCs extends to the megakaryocytic lineage.
Human Skeletal Muscle–derived CD133+ Cells Form Functional Satellite Cells After Intramuscular Transplantation in Immunodeficient Host Mice
Authors: Jinhong Meng, Soyon Chun, Rowan Asfahani, Hanns Lochmüller, Francesco Muntoni, Jennifer Morgan
Journal: Molecular Therapy (2014)

Stem cell therapy is a promising strategy for treatment of muscular dystrophies. In addition to muscle fiber formation, reconstitution of functional stem cell pool by donor cells is vital for long-term treatment. We show here that some CD133(+) cells within human muscle are located underneath the basal lamina of muscle fibers, in the position of the muscle satellite cell. Cultured hCD133(+) cells are heterogeneous and multipotent, capable of forming myotubes and reserve satellite cells in vitro. They contribute to extensive muscle regeneration and satellite cell formation following intramuscular transplantation into irradiated and cryodamaged tibialis anterior muscles of immunodeficient Rag2-/γ chain-/C5-mice. Some donor-derived satellite cells expressed the myogenic regulatory factor MyoD, indicating that they were activated. In addition, when transplanted host muscles were reinjured, there was significantly more newly-regenerated muscle fibers of donor origin in treated than in control, nonreinjured muscles, indicating that hCD133(+) cells had given rise to functional muscle stem cells, which were able to activate in response to injury and contribute to a further round of muscle regeneration. Our findings provide new evidence for the location and characterization of hCD133(+) cells, and highlight that these cells are highly suitable for future clinical application.
Survival in cancer patients hospitalized for psoriasis: a commentary
Authors: P.I. Spuls, T. Nijsten
Journal: British Journal of Dermatology (2011)

Conflicts of interest None declared. Cohort studies should include in their reporting (and so in the design) items of the STROBE statement (http://www.strobe‐statement.org) in order to avoid bias. This study fulfils many items but not all.1 The bias included should be taken into account when interpreting the results. The study is an extension of Scandinavian linkage studies from the 1990s demonstrating that patients hospitalized with psoriasis were at a higher risk of developing (smoking‐ and alcohol‐related) cancers compared with controls.2 In the introduction of this study, it is hypothesized that cancer survival is negatively affected by the systemic dysregulation of the immune system of patients with psoriasis. The main advantage of this linkage study of the Swedish Hospital Discharge Registry and the Swedish Cancer Registry is that it is population based and generates a relatively large number of patients with psoriasis. However, studying very specific patient populations such as hospitalized patients with cancer reduces the sample size rapidly. Unfortunately, no sample‐size calculations were performed to estimate the number of patients needed to achieve reliable and valid risk estimates. The authors have restricted the analysis to cancer sites that included at least 10 cases who died during the observation period, but this was not based on formal sample‐size calculations. Moreover, investigating different cancer sites may provide interesting information, but it does introduce the issue of multiple testing (> 150 survival analyses were performed implying that by chance at least seven analyses have a P‐value < 0·05, and P‐values of < 0·002 were required to be significant after Bonferroni adjustment). Therefore, a clear definition of the primary outcome is essential and subgroup analysis should be interpreted with caution.3
DIMINISHED PHENYLKETONURIA IN PHENYLPYRUVIC OLIGOPHRENIA AFTER ADMINISTRATION OF L-GLUTAMINE, L-GLUTAMATE OR L-ASPARAGINE1
Authors: Alton Meister, Sidney Udenfriend, Samuel P. Bessman
Journal: Journal of Clinical Investigation (1956)

It is well known that patients with phenylpyruvic oligophrenia excrete large amounts of phenylpyruvic acid, phenyllactic acid, and phenylalanine in the urine, and that they also exhibit an unusually high blood level of phenylalanine ( 1-4). That such patients also exhibit a markedly reduced capacity to convert phenylalanine to tyrosine was indicated by several investigations (2, 5, 6) and was proven conclusively by isotopic study (7). It has been suggested that failure to catalyze this reaction is the basic metabolic defect in this disorder (6, 7). According to this interpretation, phenylalanine accumulates, and is converted to phenylpyruvic acid and other products in greater than normal quantities. The finding of abnormally high concentrations of phenylacetylglutamine in the urine of patients with phenylpyruvic oligophrenia (8, 9) is also consistent with the increased accumulation of phenylalanine, with its conversion to phenylpyruvic acid, and transformation of the latter compound to phenylacetic acid. In man the latter compound is excreted in the urine as phenylacetylglutamine (10-12). It is reasonable to assume that the chemical defect is responsible in some way for the mental retardation of these patients; such an interpretation gains support from the observation that some patients appear to show improvement when the dietary phenylalanine intake is restricted (13-16). It seems probable that the conversion of phenylalanine to phenylpyruvic acid takes place by transamination; this mechanism has been shown to be responsible for the analogous conversion of tyrosine to p-hydroxyphenylpyruvic acid (17-19).
EXPERIMENTAL STREPTOBACILLUS MONILIFORMIS ARTHRITIS IN THE CHICK EMBRYO
Authors: G. John Buddingh
Journal: The Journal of Experimental Medicine (1944)

1. A strain of Streptobacillus moniliformis isolated from a case of rat bite fever in man has been found to produce infection of the developing chick embryo following inoculation of the chorio-allantois. 2. The disease in embryos is characterized by invasion of the blood stream and an almost exclusive localization of the infectious process to the synovial lining of the joints. 3. In the early stages of the development of the joint lesions the Streptobacillus moniliformis behaves as a facultative intracellular parasite within the cytoplasm of the synovial lining cells. Conditions favorable for the growth of the microorganisms are maintained only temporarily. The infection appears to be self-limiting in nature.