tbuckley/cabot-search huggingface dataset:
Monitoring Cerebral Blood Flow and Oxygen, Glucose, Lactate and Ammonia Metabolism
Authors: JOHN S. MEYER, F. GOTOH, M. AKIYAMA, S. YOSHITOKE
Journal: Circulation Research (1967)

New application of methods for monitoring cerebral blood flow and cerebral arteriovenous oxygen, glucose, lactate and ammonia differences are described. Results of trials of their validity in monkeys during experimental procedures are described. The apparatus includes infrared gas analyzers for monitoring arteriovenous differences after diffusion of nitrous oxide through silastic, electromagnetic flowmeters for monitoring cerebral venous outflow, the Technicon apparatus for measuring arteriovenous differences for lactate, glucose and ammonia, and the Guyton analyzer for monitoring cerebral arteriovenous oxygen differences. Cerebral blood flow in the monkey measured by the nitrous oxide method was 61 ml/100 g brain per min, cerebral oxygen consumption was 2.8 to 3.35 ml/100 g brain per min, cerebral glucose consumption was 3.52 mg/100 g brain per min, cerebral arteriovenous lactate difference was 1.1 mg/100 ml, cerebral arteriovenous ammonia difference was 2 mg/100 ml. Inhalation of 100% oxygen, 5% CO 2 in air, 20% CO 2 in air and hyperventilation caused no change in cerebral oxygen, glucose, lactate, and ammonia metabolism. During anoxic anoxia, cerebral glucose consumption increased and cerebral oxygen consumption decreased significantly. During seizures, cerebral metabolic rate for oxygen increased. No important changes in ammonia metabolism were noted. It was concluded that it is feasible to apply these methods concurrently in patients with cerebrovascular disease before and after therapeutic trials.
Serum Amyloid A in Obstructive Sleep Apnea
Authors: Anna Svatikova, Robert Wolk, Abu S. Shamsuzzaman, Tomas Kara, Eric J. Olson, Virend K. Somers
Journal: Circulation (2003)

Patients with severe obstructive sleep apnea (OSA) may have increased risk for cardiovascular and cerebrovascular diseases. Serum amyloid A (SAA) protein has recently been linked to the development of atherosclerosis, stroke, diabetes, and dementia. We tested the hypothesis that plasma SAA levels are increased in otherwise healthy subjects with OSA.Plasma SAA levels were measured in 10 male patients with moderate to severe OSA before sleep, after 5 hours of untreated OSA, and in the morning after effective continuous positive airway pressure treatment. SAA levels were also measured in 10 closely matched control subjects at similar time points. Baseline plasma SAA levels before sleep were strikingly higher in patients with moderate to severe OSA than in controls (18.8+/-2.6 versus 7.2+/-2.6 microg/mL, respectively; P=0.005) and remained unchanged in both groups throughout the night. SAA levels in 10 male patients with mild OSA were comparable with controls (P=0.46). Plasma SAA in 7 female patients with moderate to severe OSA was also markedly higher compared with matched control female subjects (24.1+/-2.4 versus 10.2+/-2.4 microg/mL, respectively; P=0.0013) but was not different from male patients with moderate to severe OSA (P=0.3). There was a significant positive correlation between SAA and apnea-hypopnea index (r=0.40, P=0.03).Plasma SAA levels are more than 2-fold greater in patients with moderate to severe OSA compared with subjects with mild OSA or healthy controls regardless of gender. Elevated SAA may contribute to any increased risk for cardiovascular and neuronal dysfunction in patients with OSA.
Kidney Donation and Risk of ESRD
Authors: Arthur J. Matas, Jonas Wadstrom, Hassan N. Ibrahim
Journal: JAMA (2014)

To the Editor Dr Muzaale and colleagues 1 matched all US kidney donors from 1994 to 2011 with a cohort of selected participants from the Third National Health and Nutrition Examination Survey (NHANES III) and found an increased cumulative incidence and lifetime risk of end-stage renal disease (ESRD) among the donors. The Editorial by Drs Gill and Tonelli 2 highlighted several methodological factors that may have biased the findings in the direction of finding increased risk to donors, and we identify an additional factor.
Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids.
Authors: I A MacPhee, F A Antoni, D W Mason
Journal: The Journal of Experimental Medicine (1989)

Lewis rats with experimental allergic encephalomyelitis (EAE), induced either by the subcutaneous injection of guinea pig myelin basic protein (MBP) or by the adoptive transfer of MBP-primed spleen cells, suffer from a single episode of paralysis from which they recover spontaneously. Animals developing EAE were found to have greatly elevated levels of corticosterone in the blood. This endogenous increase in steroid production was accompanied by lymphopenia and depressed delayed-type hypersensitivity responses to OVA, indicating that rats with EAE are immunosuppressed in an antigen-nonspecific fashion. Adrenalectomized rats given subcutaneous implants of corticosterone to maintain basal steroid levels invariably died when EAE was induced. However, if the steroid replacement therapy was adjusted to mimic the hormone levels that were observed in intact rats developing EAE, then the disease followed a nonfatal course closely resembling that seen in the nonadrenalectomized controls. Replacement therapy that achieved serum corticosterone levels slightly higher than those found in intact rats with EAE virtually suppressed the disease completely. It is concluded that endogenous corticosterone release in rats with EAE plays an essential role in the spontaneous recovery that is observed in this condition. However, the subsequent refractory phase that is characteristic of rats that have recovered from EAE induced by active immunization with MBP is not associated with chronically elevated corticosterone levels. This finding is discussed in the light of other data that suggest that unlike the spontaneous recovery, the refractory state has an immunological basis rather than an endocrinological basis.
Bioengineered Implantation of Megalin-Expressing Cells
Authors: Akihiko Saito, Junichiro J. Kazama, Noriaki Iino, Kenji Cho, Nobuo Sato, Hajime Yamazaki, Yuko Oyama, Tetsuro Takeda, Robert A. Orlando, Fujio Shimizu, Yasuhiko Tabata, Fumitake Gejyo
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Patients who have renal failure and are on dialysis therapy experience serious complications caused by low-molecular-weight uremic toxin proteins normally filtered by glomeruli and metabolized by proximal tubule cells (PTC). Dialysis-related amyloidosis is one such complication induced by systemic deposition of amyloid proteins derived from 12-kD β<sub>2</sub>-microglobulin (β<sub>2</sub>-m). Despite the use of high-flux membrane hemodialysis devices and direct absorbent columns, the removal of β<sub>2</sub>-m is suboptimal, because the effects are transient and insufficient. Megalin is expressed in the apical membranes of PTC and recognized as a multiligand endocytic receptor that binds numerous low-molecular-weight proteins, including β<sub>2</sub>-m. This study tested the feasibility of an intracorporeal therapeutic model of continuous β<sub>2</sub>-m removal using megalin-expressing cell implantation. By cell association and degradation assays, rat yolk sac-derived L2 cells were identified to internalize and degrade β<sub>2</sub>-m via megalin. The cells were effectively implanted within the subcutaneous tissues of nude mice using a type I collagen scaffold and a method inducing local angiogenesis. After nephrectomy and intraperitoneal injection with <sup>125</sup>I-β<sub>2</sub>-m, it was found that the implanted cells took up the labeled ligand, efficiently removing it from the blood. Bioengineered implantation of megalin-expressing cells may represent a new supportive therapy for dialysis patients to compensate for the loss of renal protein metabolism and remove uremic toxin proteins. E-mail: akisaito@med.niigata-u.ac.jp
Screening for Breast and Prostate Cancers: Moving Toward Transparency
Authors: David H. Newman
Journal: JNCI Journal of the National Cancer Institute (2010)

Despite mortality reductions found in early trials, recent population-based data suggest that breast and prostate cancer screening have not yielded expected benefits. Whereas evidence-based appraisals generally mistrust disease-specific mortality as a primary outcome measure, cancer screening trials have consistently used this endpoint, largely because of the impracticality of studies with enough statistical power to detect all-cause mortality reductions, which would require millions of subjects. The acceptance of disease-specific mortality as a practical surrogate for all-cause mortality may explain the discrepancy between expected and actual impact. Screening may reduce deaths from the target cancer but may increase deaths from other causes, most likely because of overdiagnosis, an increasingly recognized risk of cancer screening. Recognition of the discrepancy between the expected and the actual impact of screening and recognition of overdiagnosis as a source of harm may be critical for understanding and projecting the potential impact of cancer screening programs.
A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial
Authors: Rodger D MacArthur, Richard M Novak, Grace Peng, Li Chen, Ying Xiang, Katherine Huppler Hullsiek, Michael J Kozal, Mary van den Berg-Wolf, Christopher Henely, Barry Schmetter, Marjorie Dehlinger
Journal: The Lancet (2006)
Myocardial lactate extraction: multi-determined metabolic function.
Authors: E W Gertz, J A Wisneski, R Neese, A Houser, R Korte, J D Bristow
Journal: Circulation (1980)

Myocardial lactate production indicates anaerobic metabolism resulting from hypoxia or anoxia. Clinically, myocardial lactate extraction of less than 10% has also been used as an indicator of ischemia. Sixteen healthy young male volunteers underwent coronary sinus and aterial catheterization. A coronary sinus pacing catheter was used to obtain blood samples and increase the heart rate to twice the resting rate. Hemodynamic measurements and blood samples for lactate, free fatty acids and glucose were obtained at rest and during pacing. Seven of 16 sujects (44%) had lactate extraction of less than 10% at rest and/or at miximal pacing. No subject produced lactate. There was no correlation between myocardial lactate extraction and arterial glucose. However, lactate extraction correlated inversely with the arterial levels of free fatty acids (r = 0.67; p less than 0.01). In addition, a positive correlation was present between lactate extraction and the arterial lactate level (r = 0.78; p less than 0.01). In conclusion, myocardial lactate extraction is dependent on multiple metabolic parameters and any absolute value short of production cannot be considered abnormal.
Mouse hepatocytes and LSEC proteome reveal novel mechanisms of ischemia/reperfusion damage and protection by A2aR stimulation
Authors: Giorgia Mandili, Elisa Alchera, Simone Merlin, Chiara Imarisio, Bangalore R. Chandrashekar, Chiara Riganti, Alberto Bianchi, Francesco Novelli, Antonia Follenzi, Rita Carini
Journal: Journal of Hepatology (2014)
Ca2+ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle.
Authors: W O Hancock, D A Martyn, L L Huntsman
Journal: Circulation Research (1993)

The influence of Ca2+ and sarcomere length on myocardial crossbridge kinetics was studied in ferret papillary muscle by measuring the rate of force redevelopment following a rapid length step that dropped the force to zero. Tetanic stimulation with 5 mumol/L ryanodine was used to obtain a steady-state contraction, and segment length was measured and controlled using a sense-coil technique that measures changes in the cross-sectional area of the central region of the muscle. The rate constant for the recovery of force (ktr) following a rapid length release was obtained by fitting the data with a single exponential function. Contrary to results from skinned skeletal fibers in which ktr increases almost 10-fold from low to maximal activation levels, ktr was found not to increase at higher activation levels in this study. Similarly, although force increased with segment length under all conditions, ktr never increased with length. Data presented here are consistent with a model of myocardial Ca2+ activation in which Ca2+ modulates the number of crossbridges interacting with the thin filament and are inconsistent with a model in which Ca2+ modulates the kinetics of transitions to force producing states within the actomyosin cycle. Differences in the activation dependence of the force redevelopment rate between cardiac and skeletal muscle suggest that there are fundamental differences in the mechanism of Ca2+ activation between these two muscle types.
Complete mitochondrial DNA sequence of the fat dormouse, Glis glis: further evidence of rodent paraphyly
Authors: A. Reyes, G. Pesole, C. Saccone
Journal: Molecular Biology and Evolution (1998)

The complete mitochondrial genome of the fat dormouse, Glis glis, has been sequenced (16,602 bp). A total of 23 complete mitochondrial mammalian genomes have been taken into account for phylogenetic reconstruction. Phylogenetic analyses were performed with parsimony, distance (stationary Markov model), and maximum-likelihood methods. In all cases, data strongly support the paraphyly of rodents, with dormouse and guinea pig in a different clade from rat and mouse, reaching bootstrap values of 95%. Rodent monophyly and the existence of Glires (Rodentia and Lagomorpha) are weakly supported, with maximum bootstrap values of 11% and 8.6%, respectively. This result agrees with the analyses of isochore patterns in the nuclear genome and the B2 and B2-like retroposons, which show a close relationship between dormice and guinea pigs rather than between dormice and rats and mice.
Stages of B cell differentiation in human lymphoid tissue.
Authors: A K Bhan, L M Nadler, P Stashenko, R T McCluskey, S F Schlossman
Journal: The Journal of Experimental Medicine (1981)

Monoclonal antibodies reactive with B cell-specific differentiation and other antigens were used to investigate stages of B cell maturation in human lymphoid tissue, using an immunoperoxidase technique on frozen tissue sections. Lymphoid follicles, which represent the major anatomic compartment of B cells, demonstrated cellular antigenic expressions that appear to reflect differentiation of B cells. The majority of cells in the primary follicles and the mantle zones of secondary follicles expressed surface antigens similar to those of circulating B cells, namely IgM, IgD, Ia, B1, and B2. In contrast, the germinal center cells of secondary follicles stained for IgM, IgG, B1, B2, and Ia antigens, but not for IgD, and furthermore, acquired the T10 antigen. The germinal centers stained much more intensely than mantle zones with anti-B2, whereas no such striking difference in the staining intensity was observed with anti B1. Plasma cells, which represent the end stage of B cell differentiation, showed intense cytoplasmic staining with the anti-T10 antibody. The results indicate that the generation of germinal center cells in primary lymphoid follicles involves phenotype changes that correspond largely to those previously observed after both antigenic and mitogenic activation of B lymphocytes.
Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy
Authors: Marina Talelli, Sabrina Oliveira, Cristianne J.F. Rijcken, Ebel H.E. Pieters, Tomas Etrych, Karel Ulbrich, Rene C.F. van Nostrum, Gert Storm, Wim E. Hennink, Twan Lammers
Journal: Biomaterials (2012)
Using Electronic Health Records for Population Health Research: A Review of Methods and Applications
Authors: Joan A. Casey, Brian S. Schwartz, Walter F. Stewart, Nancy E. Adler
Journal: Annual Review of Public Health (2015)

The use and functionality of electronic health records (EHRs) have increased rapidly in the past decade. Although the primary purpose of EHRs is clinical, researchers have used them to conduct epidemiologic investigations, ranging from cross-sectional studies within a given hospital to longitudinal studies on geographically distributed patients. Herein, we describe EHRs, examine their use in population health research, and compare them with traditional epidemiologic methods. We describe diverse research applications that benefit from the large sample sizes and generalizable patient populations afforded by EHRs. These have included reevaluation of prior findings, a range of diseases and subgroups, environmental and social epidemiology, stigmatized conditions, predictive modeling, and evaluation of natural experiments. Although studies using primary data collection methods may have more reliable data and better population retention, EHR-based studies are less expensive and require less time to complete. Future EHR epidemiology with enhanced collection of social/behavior measures, linkage with vital records, and integration of emerging technologies such as personal sensing could improve clinical care and population health.
Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and correlates with inflammation
Authors: James H. Finigan, Rangnath Mishra, Vihas T. Vasu, Lori J. Silveira, David E. Nethery, Theodore J. Standiford, Ellen L. Burnham, Marc Moss, Jeffrey A. Kern
Journal: European Respiratory Journal (2012)

Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation of the epithelial human epidermal growth factor receptor (HER)2 receptor, increased pulmonary epithelial permeability and acute lung injury (ALI). We sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar lavage (BAL) and plasma from patients with ALI compared with controls and to determine whether a correlation exists between NRG-1 and inflammation and outcome in ALI. Matched BAL and plasma samples were obtained from 23 ALI patients requiring intubation and mechanical ventilation. Control patients (n=5) included healthy volunteers. NRG-1 and indices of inflammation were measured in BAL and plasma via ELISA. The mean± sd BAL NRG-1 concentration in ALI patients was 187.0±21.35 pg·mL −1 compared with 85.50±9.2 pg·mL −1 in controls (p=0.001). Increased BAL NRG-1 was associated with markers of inflammation, and inversely correlated with ventilator-free days (VFDs; r= -0.51, p=0.015). Plasma NRG-1 was elevated in ALI patients compared with controls (611.7±354.2 versus 25.17±19.33 pg·mL −1 , p&lt;0.001) and inversely correlated with VFDs (r= -0.51, p=0.04). These results confirm shedding of NRG-1 in ALI and suggest that the NRG-1–HER2 pathway is active in patients with ALI.
Epicutaneous Immunotherapy (EPIT) Is Effective and Safe to Treat Peanut Allergy: A Multi-National Double-Blind Placebo-Controlled Randomized Phase IIb Trial
Authors: Hugh A. Sampson, Wence Agbotounou, Claude Thébault, Ruban Charles, Laurent Martin, William H. Yang, Gordon L. Sussman, Terri F. Brown-Whitehorn, Kari C. Nadeau, Amarjit Singh Cheema, Stephanie A. Leonard, Jacqueline A. Pongracic, Christine Sauvage, Amal H. Assa'ad, Frederic de Blay, J. Andrew Bird, Stephen A. Tilles, Franck Boralevi, Thierry Bourrier, Wayne G. Shreffler, Jacques Hébert, Todd David Green, Roy Gerth van Wijk, André C. Knulst, Gisèle Kanny, Marek L. Kowalski, Lynda C. Schneider, Pierre Henri Benhamou, Christophe Dupont
Journal: Journal of Allergy and Clinical Immunology (2015)
Answer to letters to the editor
Authors: R de Winter
Journal: Cardiovascular Research (1999)

We thank Dr Ikeda et al. for their comments on our paper. The focus of our paper was the relationship between activation of inflammation and coagulation, as these are interrelated by the possible role of IL-6 and IL-8. The findings of Ikeda et al. concerning simultaneous elevation of coronary sinus IL-6 and von Willebrand factor is very interesting in this respect. Although cellular components of the vascular tissue, such as the endothelium, can produce IL-6, it was also shown earlier that cardiac myocytes themselves are capable of producing IL-6, especially in the setting of ischaemia/reperfusion [1]. Whether in the setting …
The anti-proliferative effects of apelin on pulmonary adventitial fibroblasts
Authors: Lauren Brash, Colin Church, Roger Wadsworth, Andrew Peacock, David Welsh
Journal: European Respiratory Journal (2012)

Background:  Pulmonary arterial hypertension (PAH) involves remodelling of the pulmonary artery resulting in right heart failure. Apelin is an endogenous peptide with physiological actions in the cardiovascular system. Pre-clinical models indicate that apelin deficiency may mediate or contribute to the pathogenesis of PAH which involves pulmonary artery fibroblasts (PAF).   Aims:  To determine if Apelin had an effect on the proliferation and migration of rat PAF.   Methods:   PAF were isolated from Sprague Dawley rats. The PAF were incubated in normoxic and hypoxic conditions (35mmHg for 24h) and proliferation in response to Apelin was assessed. The presence of the Apelin receptor (APJ) was detected by Western Blotting. PAF were also cultured to 100% confluency and the cell monolayer was scratched and cell migration was determined after incubation with Apelin.   Results:  APJ receptor was detected in PAF cells. Hypoxia alone increased the proliferation of PAF and this effect was abrogated with the addition of 200nM Apelin.  Hypoxia caused PAF migration both alone and to a higher degree with serum. The addition of Apelin prevented this migration.   Conclusions:  Apelin can reduce the increased proliferation of PAF to hypoxia and reduce the migratory capacity of these cells. Apelin may have anti-remodelling properties that require further investigation.