tbuckley/cabot-search huggingface dataset:
Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine.
Authors: G Starkebaum, J M Harlan
Journal: Journal of Clinical Investigation (1986)

We have examined whether the toxic effects of homocysteine on cultured endothelial cells could result from the formation and action of hydrogen peroxide. In initial experiments with a cell-free system, micromolar amounts of copper were found to catalyze an oxygen-dependent oxidation of homocysteine. The molar ratio of homocysteine oxidized to oxygen consumed was approximately 4.0, which suggests that oxygen was reduced to water. The addition of catalase, however, decreased oxygen consumption by nearly one-half, which suggests that H2O2 was formed during the reaction. Confirming this hypothesis, H2O2 formation was detected using the horseradish peroxidase-dependent oxidation of fluorescent scopoletin. Ceruloplasmin was also found to catalyze oxidation of homocysteine and generation of H2O2 in molar amounts equivalent to copper sulfate. Finally, homocysteine oxidation was catalyzed by normal human serum in a concentration-dependent manner. Using cultured human and bovine endothelial cells, we found that homocysteine plus copper could lyse the cells in a dose-dependent manner, an effect that was completely prevented by catalase. Homocystine plus copper was not toxic to the cells. Specific injury to endothelial cells was seen only after 4 h of incubation with homocysteine plus copper. Confirming the biochemical studies, ceruloplasmin was also found to be equivalent to Cu++ in its ability to cause injury to endothelial cells in the presence of homocysteine. Since elevated levels of homocysteine have been implicated in premature development of atherosclerosis, these findings may be relevant to the mechanism of some types of chronic vascular injury.
Widespread distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin in the lung of the normal adult rat.
Authors: J R Gosney, M C Sissons
Journal: Thorax (1985)

The nature and distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin was studied in normal adult Wistar albino rats by immunoenzyme histochemistry with the peroxidase-antiperoxidase technique.A widespread distribution of both solitary endocrine cells and neuroepithelial bodies immunoreactive for calcitonin was found.Many, but not all, were also immunoreactive for neurone specific enolase.Although both classes of cells were present in airways and parenchyma, most of the solitary cells were found in alveolar ducts and alveoli whereas most of the neuroepithelial bodies were located in bronchi and bronchioles.Bronchopulmonary endocrine cells are generally regarded as being sparse in the adult rat.It is suggested that this may be a consequence of the use of inadequate methods in attempting to identify them.So far as is known, this is the first time that calcitonin has been demonstrated by immunohistochemical methods in the lungs of rats.
Thermographic assessment of patch-test responses
Authors: A.J. BAILLIE, P.A. BIAGIONI, ANGELA FORSYTH, JENNIFER J. GARIOCH, D. MCPHERSON
Journal: British Journal of Dermatology (1990)

Infra-red thermography was used to quantify, at patch test sites, the allergic responses to experimental preparations of nickel sulphate and primary irritant responses to sodium lauryl sulphate in small groups of volunteers. The technique was also used to assess the patch-test responses in a much larger group of patients who had undergone routine patch testing for contact allergy with a wide range of test substances and among which there were large numbers of allergic, irritant and equivocal reactions. Thermographically, when compared to the surrounding normal skin surface, the sites of allergic reactions appeared as hot areas, the temperature and area of which were apparently dependent on the severity of the response. For allergic responses, there was a good correlation between the clinical assessment and either of two thermographic parameters, temperature and area of involvement. Compared with an aqueous solution of nickel sulphate, ‘poor’ formulations of the allergen, such as a suspension in soft paraffin base, elicited smaller and cooler reactions. Irritant reaction sites were not ‘hot’ and the temperature at such sites was no different from that of the surrounding normal skin. Infra-red thermography is a convenient non-invasive technique which apparently can be used to discriminate between irritant and allergic responses and to quantify the latter type of response.
The psychological burden of OSAS patients is not correlated with apnea-hypopnea index
Authors: Dionisios Bratis, Athanasios Tselebis, Anna Christodoulaki, Silvia Dumitru, Sotirios Gyftopoulos, Epaminondas Kosmas, Nikolaos Tzanakis, Michael Koutsilieris
Journal: European Respiratory Journal (2012)

Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep, which leads to the presence of excessive daytime sleepiness. Regarding the psychological comorbidity in patients diagnosed with OSAS, previous studies focused mainly on depressive and, secondarily, to anxiety symptoms.  Aims and Objectives: To record the prevalence of anxiety and depressive symptoms and of alexithymic characteristics in a sample of OSAS patients and to investigate their relation to respiratory parameter (Apnea - Hypopnea Index, AHI) of polysomnography.  Methods: The study was conducted in a certified sleep laboratory. 35 randomly selected patients were examined for anxiety, depression and alexithymia using the Spielberger Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI) and the Toronto Alexithymia Scale (TAS-20), respectively.  Results: A high prevalence of anxiety (41.4%) and depressive symptoms (55.2%) and of alexithymic characteristics (41.4%) was observed in OSAS patients. Although the control group showed a higher prevalence of anxiety (66.7%) and depressive (83.3%) symptoms, there were no differences between the two groups (t-test p> 0.05). With regard to severity, no differences were observed between subgroups (mild, moderate and severe OSAS, ANOVA p> 0.05). Women showed higher scores in BDI and STAI compared to men (t-test p   0.05).  Conclusions: This study supports the presence of a high degree of psychological burden on patients diagnosed with OSAS, regardless of the severity, as determined by the AHI.
A Surgical Case of Expanding Bilateral Coronary Aneurysms Regarded as Immunoglobulin G4-Related Disease
Authors: Yasuyuki Bito, Yasuyuki Sasaki, Hidekazu Hirai, Mitsuharu Hosono, Atsushi Nakahira, Yasuo Suehiro, Daisuke Kaku, Yuko Kubota, Makoto Miyabe, Shigefumi Suehiro
Journal: Circulation (2014)
Factors Predicting Late Recurrence for Estrogen Receptor–Positive Breast Cancer
Authors: Ivana Sestak, Mitch Dowsett, Lila Zabaglo, Elena Lopez-Knowles, Sean Ferree, J. Wayne Cowens, Jack Cuzick
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundAdjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor–positive breast cancer. We have previously shown that immunohistochemical markers (IHC4) and two gene expression profile tests (recurrence score [RS] and PAM50 risk of recurrence [ROR]) are associated with time to distant recurrence, and we have now assessed the value of each of these scores and routine clinical variables for predicting outcome, specifically in years 5 to 10.
The role of H-2 and Ia antigens in graft-versus-host reactions (GVHR). Presence of host alloantigens on donor cells after GVHR and suppression of GVHR with an anti-Ia antiserum against hose Ia antigens.
Authors: G J Prud'homme, U Sohn, T L Delovitch
Journal: The Journal of Experimental Medicine (1979)

By using an indirect immunofluorescence technique, the presence of host cell derived H-2K, H-2D, and Ia alloantigens on donor cells recovered from recipient spleens after a graft-versus-host response (GVHR) was demonstrated. Mapping studies indicated that only host K, D, and I-A region gene products could be identified on the donor cells. Host I-E/C- and I-J-subregion products were not absorbed by donor cells. Treatment of activated donor cells with anti-Ly sera plus C' revealed that donor cells carrying host Ia antigens have a Ly-1+,2-,3- phenotype, whereas donor cells carrying H-2K and H-2D host antigens have a Ly-1-,2+,3+ phenotype. A GVHR that resulted from only an I-region incompatibility was suppressed by the injection of recipient mice with an anti-Ia antiserum directed against self Ia antigens. The degree of suppression was proportional to the amount of anti-Ia antiserum administered.
Anthony’s Story
Authors: Mariana Glusman
Journal: JAMA Pediatrics (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Complex Disease–, Gene–, and Drug–Drug Interactions: Impacts of Renal Function, CYP2D6 Phenotype, and OCT2 Activity on Veliparib Pharmacokinetics
Authors: Jing Li, Seongho Kim, Xianyi Sha, Richard Wiegand, Jianmei Wu, Patricia LoRusso
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, undergoes renal excretion and liver metabolism. This study quantitatively assessed the interactions of veliparib with metabolizing enzyme (CYP2D6) and transporter (OCT2) in disease settings (renal impairment). Experimental Design: Veliparib in vitro metabolism was examined in human liver microsomes and recombinant enzymes carrying wild-type CYP2D6 or functional defect variants (CYP2D6*10 and *4). Plasma pharmacokinetics were evaluated in 27 patients with cancer. A parent–metabolite joint population model was developed to characterize veliparib and metabolite (M8) pharmacokinetics and to identify patient factors influencing veliparib disposition. A physiologically based pharmacokinetic model integrated with a mechanistic kidney module was developed to quantitatively predict the individual and combined effects of renal function, CYP2D6 phenotype, and OCT2 activity on veliparib pharmacokinetics. Results: In vitro intrinsic clearance of CYP2D6.1 and CYP2D6.10 for veliparib metabolism were 0.055 and 0.017 μL/min/pmol CYP, respectively. Population mean values for veliparib oral clearance and M8 clearance were 13.3 and 8.6 L/h, respectively. Creatinine clearance was identified as the significant covariate on veliparib oral clearance. Moderate renal impairment, CYP2D6 poor metabolizer, and co-administration of OCT2 inhibitor (cimetidine) increased veliparib steady-state exposure by 80%, 20%, and 30%, respectively. These factors collectively led to &amp;gt;2-fold increase in veliparib exposure. Conclusions: Renal function (creatinine clearance) is a significant predictor for veliparib exposure in patients with cancer. Although a single factor (i.e., renal impairment, CYP2D6 deficiency, and reduced OCT2 activity) shows a moderate impact, they collectively could result in a significant and potentially clinically relevant increase in veliparib exposure. Clin Cancer Res; 20(15); 3931–44. ©2014 AACR.
Thyroid Hormone Signaling and Homeostasis During Aging
Authors: J. Bowers, J. Terrien, M. S. Clerget-Froidevaux, J. D. Gothié, M. P. Rozing, R. G. J. Westendorp, D. van Heemst, B. A. Demeneix
Journal: Endocrine Reviews (2013)

Studies in humans and in animal models show negative correlations between thyroid hormone (TH) levels and longevity. TH signaling is implicated in maintaining and integrating metabolic homeostasis at multiple levels, notably centrally in the hypothalamus but also in peripheral tissues. The question is thus raised of how TH signaling is modulated during aging in different tissues. Classically, TH actions on mitochondria and heat production are obvious candidates to link negative effects of TH to aging. Mitochondrial effects of excess TH include reactive oxygen species and DNA damage, 2 factors often considered as aging accelerators. Inversely, caloric restriction, which can retard aging from nematodes to primates, causes a rapid reduction of circulating TH, reducing metabolism in birds and mammals. However, many other factors could link TH to aging, and it is these potentially subtler and less explored areas that are highlighted here. For example, effects of TH on membrane composition, inflammatory responses, stem cell renewal and synchronization of physiological responses to light could each contribute to TH regulation of maintenance of homeostasis during aging. We propose the hypothesis that constraints on TH signaling at certain life stages, notably during maturity, are advantageous for optimal aging.
Life History Shapes Trait Heredity by Accumulation of Loss-of-Function Alleles in Yeast
Authors: E. Zorgo, A. Gjuvsland, F. A. Cubillos, E. J. Louis, G. Liti, A. Blomberg, S. W. Omholt, J. Warringer
Journal: Molecular Biology and Evolution (2012)

A fundamental question in biology is whether variation in organisms primarily emerges as a function of adaptation or as a function of neutral genetic drift. Trait variation in the model organism baker's yeast follows population bottlenecks rather than environmental boundaries suggesting that it primarily results from genetic drift. Based on the yeast life history, we hypothesized that population-specific loss-of-function mutations emerging in genes recently released from selection is the predominant cause of trait variation within the species. As retention of one functional copy of a gene in diploid yeasts is typically sufficient to maintain completely unperturbed performance, we also conjectured that a crossing of natural yeasts from populations with different loss-of-function mutations would provide a further efficient test bed for this hypothesis. Charting the first species-wide map of trait inheritance in a eukaryotic organism, we found trait heredity to be strongly biased toward diploid hybrid performance exactly mimicking the performance of the best of the parents, as expected given a complete dominance of functional over nonfunctional alleles. Best parent heterosis, partial dominance, and negative nonadditivity were all rare phenomena. Nonadditive inheritance was observed primarily in crosses involving at least one very poor performing parent, most frequently of the West African population, and when molecularly dissected, loss-of-function alleles were identified as the underlying cause. These findings provide support for that population-specific loss-of-function mutations do have a strong impact on genotype–phenotype maps and underscores the role of neutral genetic drift as a driver for trait variation within species.
THE EFFECT OF THE BACTERIOLYTIC ENZYME OF PNEUMOCOCCUS UPON THE ANTIGENICITY OF ENCAPSULATED PNEUMOCOCCI
Authors: René J. Dubos
Journal: The Journal of Experimental Medicine (1937)

1. Mice immunized with heat-killed cells of virulent pneumococci (Type I) which have been treated with active preparations of the bacteriolytic enzyme, develop a certain degree of type specific resistance to subsequent infection. This active immunity, however, appears to be due to the small amount of free acetyl polysaccharide present in the suspension of digested bacteria, and is always of a less pronounced degree than that obtained with intact heat-killed cells. 2. Virulent pneumococci killed by heat or iodine when subjected to the action of active preparations of the bacteriolytic enzyme lose the antigenic property of stimulating in rabbits the formation of precipitating antibodies for the type specific polysaccharide. 3. The enzyme prepared from S or R pneumococci, irrespective of type derivation, is equally effective against the capsular polysaccharide antigen of any specific type of this bacterial species. 4. The inactivation of the capsular polysaccharide antigen is observed when the cells are merely rendered Gram-negative, without being caused to undergo actual disintegration or lysis. 5. These observations emphasize the importance of minimizing the chances of alterations due to the action of cellular enzymes in the course of preparation of the cell suspension to be used as immunizing agents.
The ubiquitin–proteasome system: Focus on the heart
Authors: O ZOLK, C SCHENKE, A SARIKAS
Journal: Cardiovascular Research (2006)

Proteasomes are the main non-lysosomal multicatalytic protease complexes that are involved in the degradation of most intracellular proteins. The substrate proteins are marked by ubiquitin, which serves as a tag for their regulated proteasomal destruction. One major function of the ubiquitin-proteasome system (UPS) is to prevent accumulation of non-functional, potentially toxic proteins. Moreover, it has become clear that the UPS is involved in most aspects of eukaryotic biology, such as intracellular signaling, transcriptional control, or regulation of cell death. Recent studies demonstrated that the UPS regulates receptor internalization, hypertrophic response, apoptosis, and tolerance to ischemia and reperfusion in cardiomyocytes. Since structural remodeling of the myocardium, ischemia-reperfusion injury, and myocardial cell loss are important components in the genesis of progressive heart failure, these findings suggest a pathophysiological role of the UPS. This review briefly summarizes present knowledge about structure and function of the proteasome in the heart and discusses the relevance of the UPS for cardiac diseases.
Low-carbohydrate diets for athletes: what evidence?
Authors: Timothy Noakes, Jeff S Volek, Stephen D Phinney
Journal: British Journal of Sports Medicine (2014)

<i>Objectives</i>—To assess the characteristic effects of Tai Chi Chuan (TCC) exercise on metabolism and cardiorespiratory response, and to measure its effect on cardiorespiratory function, mental control, immune capacity, and the prevention of falls in elderly people. <i>Design</i>—A review of controlled experimental studies and clinical trials designed with one of two aims: either to assess physiological responses during the performance of TCC or to assess the impact of this exercise on general health and fitness. <i>Main outcome measures</i>—Metabolic rate, heart rate, blood pressure, ventilation, maximal oxygen uptake (V̇o<sub>2</sub>max), immune capacity, falls, and fall related factors. <i>Subjects</i>—A total of 2216 men and women. <i>Results</i>—Under review were 31 original studies, published in Chinese or English journals, that met the criteria for inclusion. Most of the papers written in Chinese had not been introduced into the Western literature. Nine of these studies showed that TCC can be classified as moderate exercise, as its does not demand more than 55% of maximal oxygen intake. When this form of exercise and others conducted at equal intensity were compared, TCC showed a significantly lower ventilatory equivalent (V̇e/V̇o<sub>2</sub>max). Evidence provided by cross sectional and longitudinal studies suggests that TCC exercise has beneficial effects on cardiorespiratory and musculoskeletal function, posture control capacity, and the reduction of falls experienced by the elderly. <i>Conclusions</i>—TCC is a moderate intensity exercise that is beneficial to cardiorespiratory function, immune capacity, mental control, flexibility, and balance control; it improves muscle strength and reduces the risk of falls in the elderly.
Activation of cellular immune response in acute pancreatitis.
Authors: A Mora, M Perez-Mateo, J A Viedma, F Carballo, J Sanchez-Paya, G Liras
Journal: Gut (1997)

BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity.