tbuckley/cabot-search huggingface dataset:
Characteristics of initiation and termination of catecholamine-induced triggered activity in atrial fibers of the coronary sinus.
Authors: N Johnson, P Danilo, A L Wit, M R Rosen
Journal: Circulation (1986)

We studied epinephrine-induced delayed afterdepolarizations and triggered activity in atrial fibers from the canine coronary sinus to determine whether their responses to cardiac pacing would aid in formulating a uniform set of guidelines for differentiating this triggered activity from other arrhythmogenic mechanisms. We used standard microelectrode techniques and compared the delayed afterdepolarizations and triggered activity with those occurring in ouabain-superfused Purkinje fibers. Like Purkinje fibers, the frequency of triggering in the coronary sinus and the coupling interval of the first triggered beat were related directly to the basic drive cycle length, and the delayed afterdepolarization amplitude and frequency of triggering were related to the coupling interval of premature stimuli (S2). However, unlike Purkinje fibers, the coupling interval of the delayed afterdepolarization and of the first triggered beat were independent of the S2. Once initiated, triggered activity in the coronary sinus followed one of four rhythm patterns: in all four, the minimum and equilibrium cycle lengths were independent of the initiating cycle length. Triggered activity was terminated by overdrive and S2 pacing, especially by long episodes of overdrive at short cycle length. The first escape beat after overdrive was linearly related to the overdrive cycle length, resulting in overdrive acceleration. The return cycle length after S2 was linearly related to the S2 coupling interval. Because delayed afterdepolarizations and triggered activity in the coronary sinus respond differently to pacing from those in ouabain-superfused Purkinje fibers, triggered activity in general may not be identified by a uniform set of guidelines.
Long-term Outcomes of Bariatric Surgery
Authors: Anita P. Courcoulas, Susan Z. Yanovski, Denise Bonds, Thomas L. Eggerman, Mary Horlick, Myrlene A. Staten, David E. Arterburn
Journal: JAMA Surgery (2014)

The clinical evidence base demonstrating bariatric surgery's health benefits is much larger than it was when the National Institutes of Health last held a consensus panel in 1991. Still, it remains unclear whether ongoing studies will address critical questions about long-term complication rates and the sustainability of weight loss and comorbidity control.To summarize findings from a multidisciplinary workshop convened in May 2013 by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute. The workshop aimed to summarize the current state of knowledge of bariatric surgery, review research findings on the long-term outcomes of bariatric surgery, and establish priorities for future research directions.The evidence presented at the workshop was selected by the planning committee for both its quality and duration of follow-up. The data review emphasized randomized clinical trials and large observational studies with long-term follow-up, with or without a control group.Several small randomized clinical trials showed greater weight loss and type 2 diabetes mellitus remission compared with nonsurgical treatments within the first 2 years of follow-up after bariatric surgery. Large, long-term observational studies have shown durable (>5 years) weight loss, diabetes, and lipid improvements with bariatric surgery. Still unclear are predictors of outcomes, long-term complications, long-term survival, microvascular and macrovascular events, mental health outcomes, and costs. The studies needed to address these knowledge gaps would be expensive and logistically difficult to perform.High-quality evidence shows that bariatric surgical procedures result in greater weight loss than nonsurgical treatments and are more effective at inducing initial type 2 diabetes mellitus remission in obese patients. More information is needed about the long-term durability of comorbidity control and complications after bariatric procedures and this evidence will most likely come from carefully designed observational studies.
Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.
Authors: G P Davidson, D G Gall, M Petric, D G Butler, J R Hamilton
Journal: Journal of Clinical Investigation (1977)

To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.
Method for Estimating Confidence Levels for Measurements by Blood Glucose Monitoring Systems
Authors: Thomas M Kelly, Robert L Jensen, M Kay Robinson
Journal: Diabetes Care (1988)

A joint conference on self-monitoring of blood glucose (SMBG) has proposed that all glucose monitoring systems generate values that are within 10% of the actual blood glucose level 100% of the time. To estimate the confidence limits of blood glucose measurements made in a typical university ambulatory care setting and to ascertain whether they met the proposed standard, we performed duplicate determinations of blood glucose using a reflectance meter and applied to the measurements a method for calculating the closeness of measured values to a “true” mean. Based on paired measurements in 100 consecutive diabetic subjects, we were able to show that one measurement would be within 11.9% of a true mean value 95% of the time and within 8.4% of the mean 90% of the time. The 95 and 90% confidence limits for the average of two repeated measurements were calculated to be 8.4 and 5.9%, respectively. Our methodology can be applied to any set of SMBG values to calculate their confidence limits and to determine whether the measurements meet recommended standards.
The Influence of Stress Hormones on Fear Circuitry
Authors: Sarina M. Rodrigues, Joseph E. LeDoux, Robert M. Sapolsky
Journal: Annual Review of Neuroscience (2009)

Fear arousal, initiated by an environmental threat, leads to activation of the stress response, a state of alarm that promotes an array of autonomic and endocrine changes designed to aid self-preservation. The stress response includes the release of glucocorticoids from the adrenal cortex and catecholamines from the adrenal medulla and sympathetic nerves. These stress hormones, in turn, provide feedback to the brain and influence neural structures that control emotion and cognition. To illustrate this influence, we focus on how it impacts fear conditioning, a behavioral paradigm widely used to study the neural mechanisms underlying the acquisition, expression, consolidation, reconsolidation, and extinction of emotional memories. We also discuss how stress and the endocrine mediators of the stress response influence the morphological and electrophysiological properties of neurons in brain areas that are crucial for fear-conditioning processes, including the amygdala, hippocampus, and prefrontal cortex. The information in this review illuminates the behavioral and cellular events that underlie the feedforward and feedback networks that mediate states of fear and stress and their interaction in the brain.
Vitamin E decreases bone mass by stimulating osteoclast fusion
Authors: Koji Fujita, Makiko Iwasaki, Hiroki Ochi, Toru Fukuda, Chengshan Ma, Takeshi Miyamoto, Kimitaka Takitani, Takako Negishi-Koga, Satoko Sunamura, Tatsuhiko Kodama, Hiroshi Takayanagi, Hiroshi Tamai, Shigeaki Kato, Hiroyuki Arai, Kenichi Shinomiya, Hiroshi Itoh, Atsushi Okawa, Shu Takeda
Journal: Nature Medicine (2012)
Prostaglandins and renin release: the effect of PGI2, PGE2, and 13,14-dihydro PGE2 on the baroreceptor mechanism of renin release in the dog.
Authors: J G Gerber, R T Keller, A S Nies
Journal: Circulation Research (1979)

We compared the ability of the vasodilator prostaglandins PGI2, PGE2, and 13,14-dihydro PGE2 to release renin when infused into the denervated, nonfiltering canine kidney in vivo. Papaverine was used as a nonprostaglandin vasodilator. All the prostaglandins tested were capable of stimulating renin secretion, with the scale of potency being 13,14-dihydro PGE2 greater than PGI2 greater than PGE2; papaverine had no effect on renin secretion. These results indicate that both PGE2 and PGI2 can stimulate renin secretion but that vasodilation per se is not a stimulus. 13,14-Dihydro PGE2 was included because it is a poorer substrate than PGE2, both for transport into cells and catabolism to inactive products, but has comparable potency to PGE2 when tested in systems with limited ability to catabolize PGE2. The fact that 13,14-dihydro PGE2 was the most potent prostaglandin tested suggests that the effects of PGE2 in our system are reduced by the kidneys' recognized ability to extract and catabolize PGE2. Since PGI2 is less avidly metabolized than PGE2 by the kidney, the differences in observed potency between PGE2 and PGI2 could be largely the result of differences in renal catabolism of the two prostaglandins rather than differences in intrinsic potency. Therefore, both PGE2 and PGI2 are candidates for the endogenous prostaglandin responsible for stimulating renin secretion.
Dynamics of Renal Histamine in Normal Rat Kidney and in Nephrosis Induced by Aminonucleoside of Puromycin
Authors: Hanna E. Abboud, S. L. Ou, J. A. Velosa, Sudhir V. Shah, Thomas P. Dousa
Journal: Journal of Clinical Investigation (1982)

Histamine is known to have a profound effect on capillary permeability in nonrenal tissues and this effect is presumably mediated by cyclic (c)AMP. Because in our previous experiments we found that histamine stimulates cAMP accumulation in glomeruli (Torres, V. E., T. E. Northryn, R. M. Edwards, S. V. Shah, and T. P. Dousa. 1978. Modulation of cyclic nucleotides in isolated rat glomeruli. J. Clin. Invest.62: 1334.), we now explored whether this amine is formed in renal tissue, namely in glomeruli, and whether its renal metabolism is altered in experimental nephrosis induced by puromycin aminonucleoside (PA) in rats. In normal rats, histamine content was higher (Delta + 240%) in cortex than in medulla. In glomeruli isolated from renal cortex, histamine content was significantly higher (Delta + 260%) than in tubules. Incubation of isolated glomeruli with l-histidine resulted in a time-dependent increase of histamine content in glomeruli, but no change was found in tubules. The increase in glomerular histamine was blocked by the histidine decarboxylase inhibitor bromocresine. In rats with PA nephrosis induced by a single intraperitoneal injection of PA (15 mg/100 g body wt) urinary excretion of histamine was markedly increased (>Delta + 200%), but control rats did not differ from rats with PA nephrosis in urinary excretions of l-histidine and of creatinine. At the peak of proteinuria (day 9 after injection of PA) the plasma level of histamine was slightly elevated, and plasma histidine slightly decreased in animals that developed PA nephrosis. The content of histamine was markedly higher and the level of histidine was significantly lower in the renal cortex of PA-nephrotic rats as compared with controls; PA-nephrotic and control rats did not differ in the content of histidine and histamine in the liver. In addition, the content of histamine was higher in glomeruli isolated from PA-nephrotic rats; lesser difference was found in cortical tubules. The results further indicate that PA-nephrotic rats have higher content of histamine in the renal cortex, predominently in glomeruli with increased urinary histamine excretion. The elevated renal cortical histamine is not due to higher availability of histamine precursor l-histidine. Results thus show that glomeruli are a major site of intrarenal histamine synthesis and accumulation, and also suggest that abnormal renal metabolism of this amine in PA nephrosis may be related, as a cause or as a consequence, to the pathogenesis of this disease.
Relapse and Late Mortality in 5-Year Survivors of Myeloablative Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia in First Chronic Phase
Authors: John M. Goldman, Navneet S. Majhail, John P. Klein, Zhiwei Wang, Kathleen A. Sobocinski, Mukta Arora, Mary M. Horowitz, J. Douglas Rizzo
Journal: Journal of Clinical Oncology (2010)

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for chronic myeloid leukemia (CML), but its long-term outcomes are not well described. We studied the long-term outcomes of CML patients in first chronic phase who receive an allogeneic HCT. PATIENTS AND METHODS Our study included 2,444 patients who received myeloablative HCT for CML in first chronic phase between 1978 and 1998 and survived in continuous complete remission for at least 5 years (median follow-up, 11 years; range, 5 to 25 years). Donor sources were human leukocyte antigen-matched siblings in 1,692 patients, unrelated donors in 639 patients, and other related donors in 113 patients. RESULTS Overall survival rates at 15 years were 88% (95% CI, 86% to 90%) for sibling HCT and 87% (95% CI, 83% to 90%) for unrelated donor HCT. Corresponding cumulative incidences of relapse were 8% (95% CI, 7% to 10%) and 2% (95% CI, 1% to 4%), respectively. The latest relapse was reported 18 years post-HCT. In multivariable analyses, history of chronic graft-versus-host disease increased risks of late overall mortality and nonrelapse mortality but reduced risks of relapse. In comparison with age-, race-, and sex-adjusted normal populations, the mortality of HCT recipients was significantly higher until 14 years post-HCT; thereafter, mortality rates were similar to those of the general population (relative mortality ratio at 15 years, 2.3; 95% CI, 0 to 4.9). CONCLUSION Recipients of allogeneic HCT for CML in first chronic phase who remain in remission for at least 5 years have favorable subsequent long-term survival, and their mortality rates eventually approach those of the general population.
Mitochondrial Gene Transfer in Pieces: Fission of the Ribosomal Protein Gene rpl2 and Partial or Complete Gene Transfer to the Nucleus
Authors: Keith L. Adams, Han Chuan Ong, Jeffrey D. Palmer
Journal: Molecular Biology and Evolution (2001)

Mitochondrial genes are usually conserved in size in angiosperms. A notable exception is the rpl2 gene, which is considerably shorter in the eudicot Arabidopsis than in the monocot rice. Here, we show that a severely truncated mitochondrial rpl2 gene (termed 5′ rpl2) was created by the formation of a premature stop codon early in eudicot evolution. This 5′ rpl2 gene was subsequently lost many times from the mitochondrial DNAs of 179 core eudicots surveyed by Southern hybridization. The sequence corresponding to the 3′ end of rice rpl2 (termed 3′ rpl2) has been lost much more pervasively among the mitochondrial DNAs of core eudicots than has 5′ rpl2. Furthermore, where still present in these mitochondrial genomes, 3′ rpl2 always appears to be a pseudogene, and there is no evidence that 3′ rpl2 was ever a functional mitochondrial gene. An intact and expressed 3′ rpl2 gene was discovered in the nucleus of five diverse eudicots (tomato, cotton, Arabidopsis, soybean, and Medicago). In the first three of these species, 5′ rpl2 is still present in the mitochondrion, unlike the two legumes, where both parts of rpl2 are present in the nucleus as separate genes. The full-length rpl2 gene has been transferred intact to the nucleus in maize. We propose that the 3′ end of rpl2 was functionally transferred to the nucleus early in eudicot evolution, and that this event then permitted the nonsense mutation that gave rise to the mitochondrial 5′ rpl2 gene. Once 5′ rpl2 was established as a stand-alone mitochondrial gene, it was then lost, and was probably transferred to the nucleus many times. This complex history of gene fission and gene transfer has created four distinct types of rpl2 structures or compartmentalizations in angiosperms: (1) intact rpl2 gene in the mitochondrion, (2) intact gene in the nucleus, (3) split gene, 5′ in the mitochondrion and 3′ in the nucleus, and (4) split gene, both parts in the nucleus.
Six minute walking distance in healthy elderly subjects
Authors: T. Troosters, R. Gosselink, M Decramer
Journal: European Respiratory Journal (1999)

Age-related memory impairments have been associated with structural changes in the dopaminergic system, but the underlying mechanisms remain unclear. Recent work indicates that iron accumulation might be of particular relevance. As iron accumulates, a degeneration of myelin sheaths has been observed in the elderly, but the relationship between both and their impact on memory performance in healthy elderly humans remain important open questions. To address this issue, we combined an established behavioral paradigm to test memory performance [verbal learning memory test (VLMT)] with state of the art quantitative magnetic resonance imaging techniques allowing us to quantify the degree of myelination and iron accumulation via markers of tissue microstructure in a group of young (18–32 years) and healthy elderly humans (55–79 years). As expected, we observed a decrease in gray matter volume and myelin, and an increase of iron in the elderly relative to the young subjects within widespread brain regions, including the basal ganglia. Furthermore, higher levels of iron within the ventral striatum were accompanied by a negative correlation between myelin and iron specific for the elderly participants. Importantly, both markers of iron and myelin (and their ratio) predicted the performance of the elderly in the VLMT. This suggests that ventral striatum iron accumulation is linked to demyelination and impairments in declarative memory. Together, our data provide novel insights into underlying microstructural mechanisms of memory decline in the elderly. <b>SIGNIFICANCE STATEMENT</b> Memory decline in healthy elderly is a common phenomenon, but the underlying neural mechanisms remain unclear. We used a novel approach that allowed us to combine behavior and whole-brain measures of iron, myelin, and gray matter in the participant9s individual subspace to analyze structure–structure and structure–behavior interactions. We were able to show, that age-related high levels of iron are accompanied by a negative correlation of iron and myelin in the ventral striatum, which predicted individual memory performance. As such, our findings provide unprecedented insights into the basic mechanisms of memory decline in the elderly.
Benchmark Calculations for Perchlorate from Three Human Cohorts
Authors: Kenny S. Crump, John P. Gibbs
Journal: Environmental Health Perspectives (2005)

The presence of low concentrations of perchlorate in some drinking water sources has led to concern regarding potential effects on the thyroid. In a recently published report, the National Academy of Sciences indicated that the perchlorate dose required to cause hypothyroidism in adults would probably be > 0.40 mg/kg-day for months or longer. In this study, we calculated benchmark doses for perchlorate from thyroid-stimulating hormone (TSH) and free thyroxine (T4) serum indicators from two occupational cohorts with long-term exposure to perchlorate, and from a clinical study of volunteers exposed to perchlorate for 2 weeks. The benchmark dose for a particular serum indicator was defined as the dose predicted to cause an additional 5 or 10% of persons to have a serum measurement outside of the normal range. Using the data from the clinical study, we estimated the half-life of perchlorate in serum at 7.5 hr and the volume of distribution at 0.34 L/kg. Using these estimates and measurements of perchlorate in serum or urine, doses in the occupational cohorts were estimated and used in benchmark calculations. Because none of the three studies found a significant effect of perchlorate on TSH or free T4, all of the benchmark dose estimates were indistinguishable from infinity. The lower 95% statistical confidence limits on benchmark doses estimated from a combined analysis of the two occupational studies ranged from 0.21 to 0.56 mg/kg-day for free T4 index and from 0.36 to 0.92 mg/kg-day for TSH. Corresponding estimates from the short-term clinical study were within these ranges.
STUDIES BY ELECTRON MICROSCOPY OF THIN SECTIONS OF INFECTIOUS MYXOMATOSIS IN RABBITS
Authors: B. Epstein, Magdalena Reissig, E. De Robertis
Journal: The Journal of Experimental Medicine (1952)

Rabbits were inoculated with the C.P.M. strain of myxoma virus and the resulting subcutaneous tumors were fixed, embedded, and sectioned for observation with the electron microscope. Both round cells and the typical stellate myxomatous cells were observed in addition to changes in the collagen pattern at the intercellular spaces. The cytoplasm of the cells showed a great number of bodies of varying size and density, the largest of them having the size and other characteristics of the elementary bodies of the virus. Some of the bodies showed an internal structure, being formed by the tight clumping of small dense particles. Distribution curves of the diameter of the elementary bodies and of the smaller internal particles are presented. The morphological problems involved in the virus-host cell relationship are discussed in the case of the myxoma virus.
A life-threatening complication of a life-saving manoeuvre
Authors: Y.-Y. Chen, M.-S. Soon, H.-H. Yen, H.-K. Wu
Journal: Gut (2007)

An 80-year-old woman had airway obstruction while eating dinner at home. She became rapidly cyanotic and then unresponsive. A family member performed the Heimlich manoeuvre, which resulted in a successful dislodgement …
Designed calibration: Naturally selected flexibility, not non-genetic inheritance
Authors: Thomas E. Dickins, Benjamin J. A. Dickins
Journal: Behavioral and Brain Sciences (2007)

Abstract Jablonka &amp; Lamb (J&amp;L) have presented a number of different possible mechanisms for finessing design. The extra-genetic nature of these mechanisms has led them to challenge orthodox neo-Darwinian views. However, these mechanisms are for calibration and have been designed by natural selection. As such, they add detail to our knowledge, but neo-Darwinism is sufficiently resourced to account for them.