tbuckley/cabot-search huggingface dataset:
Physiology and Pathophysiology of Heme
Authors: Michal J. Tracz, Jawed Alam, Karl A. Nath
Journal: Journal of the American Society of Nephrology (2007)

An iron-containing, tetrapyrrole ring, heme is an essential prosthetic group in an array of proteins that comprehensively affect cellular function and metabolism; yet "free" heme in sufficient amounts can be damaging to the kidney and other organs because of its bioreactivity and pro-oxidant effects. This review discusses the cellular metabolism of heme in health and disease and covers such areas as the synthesis of heme and its utilization in heme proteins; mechanisms underlying the toxicity of heme; and the extent to which pathophysiologic processes, such as renal incorporation of heme proteins or destabilization of intracellular heme proteins, increase intracellular levels of heme and provoke renal injury. The main catabolic process that degrades heme, the heme oxygenase (HO) system, is reviewed, and evidence for the protective effects of HO-1 against acute and chronic heme/heme protein-induced renal injury is summarized. Finally, current views regarding the molecular basis for heme-induced upregulation of HO-1 are discussed.
Depression Screening Disparities Among Veterans With Diabetes Compared With the General Veteran Population
Authors: Laura E. Jones, Caroline Carney Doebbeling
Journal: Diabetes Care (2007)

We sought to describe the proportion of veterans with diabetes screened for depression compared with the general population of veterans.Electronic medical records (fiscal years 2001-2004) from a Midwestern Veterans Health Administration (VHA) facility and VHA External Peer Review Program (EPRP) data were used for the study. Facility-level data included inpatient and outpatient encounters, which included depression screen results. EPRP data were facility-level summary data, which detailed the proportion of general population veterans nationwide and patients at the Midwestern facility who were screened for depression. Logistic regression tested for associations between depression screen receipt and screening positive and demographic/clinical characteristics among patients with diabetes.Depression screening among those with diabetes improved from 62% in fiscal year 2001 to 83% in 2004. Screening was 9-23% lower and 11-22% lower in patients with diabetes compared with the general population of veterans nationwide and patients at the Midwestern facility, respectively. Seventeen percent of subjects with diabetes screened positive, which is two times higher than in the general population. Women (odds ratio 0.45 [95% CI 0.35-0.60]) and subjects with unknown A1C (0.40 [0.34-0.46]) were less likely to be screened for depression. A >or=50% service-connected disability rating was inversely associated with screening (0.84 [0.72-0.99]) but positively associated with screening positive for depression (1.56 [1.33-1.82]).Screening for depression among veterans with diabetes improved 21% but is considerably lower than the proportion of general population veterans screened nationally and at the facility of interest. Targeted interventions to improve screening in patients with diabetes are required based on evidence that screening translates into increased provider recognition and treatment of depression.
Self esteem and health
Authors: M. Marmot
Journal: BMJ (2003)

Autonomy, self esteem, and health are linked together 

The starting point for Richard Sennett's recent book, Respect in a World of Inequality , is that society is riddled with inequality: of natural endowment and talent, of opportunities and life chances, and of achievement.1 We respect achievement. Hence these inequalities will be accompanied by inequality of respect. This, in turn, will be accompanied by inequalities in self esteem. Do such inequalities in self esteem matter? And if they do, is there anything to be done given that there will always be individual differences in earned respect?

The answer to both questions is probably yes—they do matter, and something can be done. There is a view that human needs form a hierarchy: keeping life and limb together takes precedence over such concerns as self esteem and respect. Doyal and Gough criticise this concept of hierarchy of needs and replace it with the idea that there are two basic human needs—health and autonomy.2 Autonomy is closely linked with self esteem and the earning of respect.1 Individuals do not worry about the means of achieving good health and only then concern themselves with autonomy. Both are basic and, I …
Generation of Induced Pluripotent Stem Cells from Human Kidney Mesangial Cells
Authors: Bi Song, Jonathan C. Niclis, Maliha A. Alikhan, Samy Sakkal, Aude Sylvain, Peter G. Kerr, Andrew L. Laslett, Claude A. Bernard, Sharon D. Ricardo
Journal: Journal of the American Society of Nephrology (2011)

Glomerular injury and podocyte loss leads to secondary tubulointerstitial damage and the development of fibrosis. The possibility of genetically reprogramming adult cells, termed induced pluripotent stem cells (iPS), may pave the way for patient-specific stem-cell-based therapies. Here, we reprogrammed normal human mesangial cells to pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4 and c-Myc). The kidney iPS (kiPS) cells resembled human embryonic stem-cell-like colonies in morphology and gene expression: They were alkaline phosphatase-positive; expressed OCT3/4, TRA-1 to 60 and TRA-1 to 81 proteins; and showed downregulation of mesangial cell markers. Quantitative (qPCR) showed that kiPS cells expressed genes analogous to embryonic stem cells and exhibited silencing of the retroviral transgenes by the fourth passage of differentiation. Furthermore, kiPS cells formed embryoid bodies and expressed markers of all three germ layers. The injection of undifferentiated kiPS colonies into immunodeficient mice formed teratomas, thereby demonstrating pluripotency. These results suggest that reprogrammed kidney induced pluripotent stem cells may aid the study of genetic kidney diseases and lead to the development of novel therapies.
Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia
Authors: M J Schultz
Journal: Thorax (2004)

<b>Background:</b> Fibrin deposition is a hallmark of pneumonia. To determine the kinetics of alterations in local coagulation and fibrinolysis in relation to ventilator associated pneumonia (VAP), a single centre prospective study of serial changes in pulmonary and systemic thrombin generation and fibrinolytic activity was conducted in patients at risk for VAP. <b>Methods:</b> Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require mechanical ventilation for more than 5 days. A total of 28 patients were studied, nine of whom developed VAP. <b>Results:</b> In patients who developed VAP a significant increase in thrombin generation was observed in the airways, as reflected by a rise in the levels of thrombin-antithrombin complexes in NBL fluid accompanied by increases in soluble tissue factor and factor VIIa concentrations. The diagnosis of VAP was preceded by a decrease in fibrinolytic activity in NBL fluid. Indeed, before VAP was diagnosed clinically, plasminogen activator activity levels in NBL fluid gradually declined, which appeared to be caused by a sharp increase in NBL fluid levels of plasminogen activator inhibitor 1. <b>Conclusion:</b> VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP.
Zileuton Provides Significant Improvement in Asthma Symptoms and β-agonist and Rescue Medication Use Compared to Placebo in Asthma Patients with Reduced or Low Lung Function
Authors: R.A. Nathan, B.M. Prenner, J.A. Bernstein, K. Walton-Bowen
Journal: Journal of Allergy and Clinical Immunology (2006)
Leptin Predicts Diabetes but Not Cardiovascular Disease
Authors: Paul Welsh, Heather M. Murray, Brendan M. Buckley, Anton J.M. de Craen, Ian Ford, J. Wouter Jukema, Peter W. Macfarlane, Chris J. Packard, David J. Stott, Rudi G.J. Westendorp, James Shepherd, Naveed Sattar
Journal: Diabetes Care (2008)

OBJECTIVE—To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women. RESEARCH DESIGN AND METHODS—We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up. RESULTS—In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90–1.16] per unit log-leptin increase) or women (1.05 [0.91–1.20]) but was associated with risk of diabetes in men (2.75 [2.14–3.52]) and women (1.54 [1.22–1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30–2.63]) but not in women (0.89 [0.64–1.26]). CONCLUSIONS—Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly.
Gain of HIF-1α under Normoxia in Cancer Mediates Immune Adaptation through the AKT/ERK and VEGFA Axes
Authors: Young-Ho Lee, Hyun Cheol Bae, Kyung Hee Noh, Kwon-Ho Song, Sang-kyu Ye, Chih-Ping Mao, Kyung-Mi Lee, T.-C. Wu, Tae Woo Kim
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Adaptation to host immune surveillance is now recognized as a hallmark of cancer onset and progression, and represents an early, indispensable event in cancer evolution. This process of evolution is first instigated by an immune selection pressure imposed by natural host surveillance mechanisms and may then be propagated by vaccination or other types of immunotherapy. Experimental Design: We developed a system to simulate cancer evolution in a live host and to dissect the mechanisms responsible for adaptation to immune selection. Here, we show that the oxygen-sensitive α subunit of hypoxia-inducible factor 1 (HIF-1α) plays a central role in cancer immune adaptation under conditions of normal oxygen tension. Results: We found that tumor cells gain HIF-1α in the course of immune selection under normoxia and that HIF-1α renders tumor cells resistant to lysis by tumor-specific cytotoxic T lymphocytes (CTL) in culture and in mice. The effects of HIF-1α on immune adaptation were mediated through VEGFA-dependent activation of the AKT and ERK signaling pathways, which induced an antiapoptotic gene expression network in tumor cells. Conclusions: Our study therefore establishes a link between immune selection, overexpression of HIF-1α, and cancer immune adaptation under normoxia, providing new opportunities for molecular intervention in patients with cancer. Clin Cancer Res; 21(6); 1438–46. ©2015 AACR.
Effects of Alcoholism and Gender on Brain Metabolism
Authors: Brian C. Schweinsburg, Omar M. Alhassoon, Michael J. Taylor, Raul Gonzalez, John S. Videen, Gregory G. Brown, Thomas L. Patterson, Igor Grant
Journal: American Journal of Psychiatry (2003)

Proton magnetic resonance spectroscopy was used to evaluate gender influences on alcohol-associated changes in brain metabolism.Concentrations of N-acetylaspartate, choline-containing compounds, myo-inositol, and creatine plus phosphocreatine in frontal lobe gray matter and white matter were estimated in eight women and 17 men who were recently detoxified from long-term alcoholism. Twelve women and 13 men with no history of alcoholism were used as a comparison group.In male and female alcoholics, frontal lobe white matter concentrations of N-acetylaspartate were significantly lower (-8.8%) than those seen in nonalcoholic comparison subjects. In the frontal lobe gray matter region, a significant alcoholism status-by-gender interaction and follow-up analyses revealed that female alcoholics had significantly lower N-acetylaspartate concentrations (-10.73%) relative to female comparison subjects, while male alcoholics and male comparison subjects had similar levels of this metabolite (<1% difference).Lower concentrations of white matter N-acetylaspartate, which may indicate neuronal loss or dysfunction, is equally severe in men and women with comparable alcohol abuse histories. However, female alcoholics exhibited significantly less N-acetylaspartate in frontal gray matter relative to female nonalcoholic comparison subjects, which could mean that female alcoholics are more susceptible to gray matter injury than their male counterparts. However, this finding could also be explained by higher-than-expected levels of N-acetylaspartate in the healthy female comparison group.
Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice
Authors: RM Steinman, B Gutchinov, MD Witmer, MC Nussenzweig
Journal: The Journal of Experimental Medicine (1983)

Clone 33D1 is a mouse-rat hybridoma that secretes a specific anti-dendritic cell (DC) monoclonal antibody (14). Because the antibody kills DC in the presence of rabbit complement, it can be used to study the functional consequences of selective DC depletion. Previous data on the cell specificity of 33D1 were first extended. By cytotoxicity (rabbit complement) and indirect immunofluorescence (biotin-avidin technique), 33D1 reacted with DC but not with macrophages nor other splenocytes. In contrast, the monoclonal antibody, F4/80 (15), reacted with macrophages but not DC. The functional assay evaluated in this paper was stimulation of the primary mixed leukocyte reaction (MLR). 33D1 antibody itself did not inhibit stimulation by enriched populations of DC. In the presence of complement, 33D1 killed DC and ablated stimulatory function. The effect of 33D1 and complement on MLR stimulation by heterogenous cell mixtures was then evaluated. Removal of DC from unfractionated spleen suspensions reduced stimulatory capacity 75-90 percent, comparable to that produced with specific anti-Ia antibody and complement. Stimulation of both proliferative and cytotoxic responses was reduced. DC depletion had similar effects on MLR generated across full strain differences, or across selected subregions (H2I, H-2K/D) of the major histocompatibility complex. To further compare the functional properties of spleen DC and macrophages, MLR stimulation by adherent and nonadherent fractions of spleen were tested separately. 62 +/- 8 percent of the total stimulatory capacity of spleen was in the plastic adherent population. Activity was ablated greater than 90 percent after elimination of DC. MLR stimulation by 24-h cultures of spleen adherent cells, which contained a three- to sixfold excess of Ia(+) macrophages, was also ablated when DC were removed. Stimulation by nonadherent spleen was more resistant, but was reduced 50-75 percent by 33D1 and complement. The function of spleen cells treated with 33D1 or anti-Ia antibody and complement was restored with a small inoculum of purified DC. The latter corresponded to 0.5 percent of total stimulator cells and were enriched by previously described techniques that did not require the 33D1 antibody. We conclude that the DC, a trace component of mouse spleen, is the principal cell type required for stimulation of the primary MLR. Because other cells are not immunogenic, but do express Ia and H-2 alloantigens, DC likely represent the critical accessory cell required for the induction of lymphocyte responses.
Human Papillomavirus–Negative Pharyngeal Cancer
Authors: Magnus T. Dillon, Kevin J. Harrington
Journal: Journal of Clinical Oncology (2015)

Human papillomavirus–negative head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, and despite optimal treatment with chemoradiotherapy to the limit of tolerance, many patients will relapse. A number of methods for intensifying treatment of HNSCC have been investigated, leading to the current standards of care. Novel agents targeting tumor cell and stromal signaling, DNA damage response, and immune system are now reaching clinical trials in combination with chemoradiotherapy. In this review, we discuss the evidence for the current treatment of locally advanced human papillomavirus–negative HNSCC, as well as investigational therapies, such as hypoxia modification, molecular targeting of epidermal growth factor receptor family, vascular endothelial growth factor receptor or DNA damage response proteins in combination with radiation therapy.
(10) Case for diagnosis
Authors: J.D.T. Kilby
Journal: British Journal of Dermatology (1973)

Journal Article (10) Case for diagnosis Get access J.D.T. Kilby J.D.T. Kilby Department of Dermatology, Bristol Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue s9, 1 July 1973, Pages 51–53, https://doi.org/10.1111/j.1365-2133.1973.tb03443.x Published: 01 July 1973
Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing
Authors: Timothy J. Wells, Deborah Whitters, Yanina R. Sevastsyanovich, Jennifer N. Heath, John Pravin, Margaret Goodall, Douglas F. Browning, Matthew K. O’Shea, Amy Cranston, Anthony De Soyza, Adam F. Cunningham, Calman A. MacLennan, Ian R. Henderson, Robert A. Stockley
Journal: The Journal of Experimental Medicine (2014)

Although specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody-dependent enhancement of bacterial infection is largely unrecognized. Here, we demonstrate that in a significant portion of patients with bronchiectasis and Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from complement-mediated killing. Strains that resist antibody-induced, complement-mediated killing produce lipopolysaccharide containing O-antigen. The inhibition of antibody-mediated killing is caused by excess production of O-antigen-specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill strains with long-chain O-antigen. Patients with impaired serum-mediated killing of P. aeruginosa by IgG2 have poorer respiratory function than infected patients who do not produce inhibitory antibody. We suggest that excessive binding of IgG2 to O-antigen shields the bacterium from other antibodies that can induce complement-mediated killing of bacteria. As there is significant sharing of O-antigen structure between different Gram-negative bacteria, this IgG2-mediated impairment of killing may operate in other Gram-negative infections. These findings have marked implications for our understanding of protection generated by natural infection and for the design of vaccines, which should avoid inducing such blocking antibodies.
1,5-Anhydroglucitol and Postprandial Hyperglycemia as Measured by Continuous Glucose Monitoring System in Moderately Controlled Patients With Diabetes
Authors: Kathleen M. Dungan, John B. Buse, Joseph Largay, Mary M. Kelly, Eric A. Button, Shuhei Kato, Steven Wittlin
Journal: Diabetes Care (2006)

Postprandial hyperglycemia is often inadequately assessed in diabetes management. Serum 1,5-anhydroglucitol (1,5-AG) drops as serum glucose rises above the renal threshold for glucose and has been proposed as a marker for postprandial hyperglycemia. The objective of this study is to demonstrate the relationship between 1,5-AG and postprandial hyperglycemia, as assessed by the continuous glucose monitoring system (CGMS) in suboptimally controlled patients with diabetes.Patients with type 1 or type 2 diabetes and an HbA(1c) (A1C) between 6.5 and 8% with stable glycemic control were recruited from two sites. A CGMS monitor was worn for two consecutive 72-h periods. Mean glucose, mean postmeal maximum glucose (MPMG), and area under the curve for glucose above 180 mg/dl (AUC-180), were compared with 1,5-AG, fructosamine (FA), and A1C at baseline, day 4, and day 7.1,5-AG varied considerably between patients (6.5 +/- 3.2 mug/ml [means +/- SD]) despite similar A1C (7.3 +/- 0.5%). Mean 1,5-AG (r = -0.45, P = 0.006) correlated with AUC-180 more robustly than A1C (r = 0.33, P = 0.057) or FA (r = 0.38, P = 0.88). MPMG correlated more strongly with 1,5-AG (r = -0.54, P = 0.004) than with A1C (r = 0.40, P = 0.03) or FA (r = 0.32, P = 0.07).1,5-AG reflects glycemic excursions, often in the postprandial state, more robustly than A1C or FA. 1,5-AG may be useful as a complementary marker to A1C to assess glycemic control in moderately controlled patients with diabetes.
Extracellular Matrix Secretion by Cardiac Fibroblasts
Authors: Mélanie Abonnenc, Adam A. Nabeebaccus, Ursula Mayr, Javier Barallobre-Barreiro, Xuebin Dong, Friederike Cuello, Sumon Sur, Ignat Drozdov, Sarah R. Langley, Ruifang Lu, Konstantina Stathopoulou, Athanasios Didangelos, Xiaoke Yin, Wolfram-Hubertus Zimmermann, Ajay M. Shah, Anna Zampetaki, Manuel Mayr
Journal: Circulation Research (2013)

Rationale: MicroRNAs (miRNAs), in particular miR-29b and miR-30c, have been implicated as important regulators of cardiac fibrosis. Objective: To perform a proteomics comparison of miRNA effects on extracellular matrix secretion by cardiac fibroblasts. Methods and Results: Mouse cardiac fibroblasts were transfected with pre-/anti-miR of miR-29b and miR-30c, and their conditioned medium was analyzed by mass spectrometry. miR-29b targeted a cadre of proteins involved in fibrosis, including multiple collagens, matrix metalloproteinases, and leukemia inhibitory factor, insulin-like growth factor 1, and pentraxin 3, 3 predicted targets of miR-29b. miR-29b also attenuated the cardiac fibroblast response to transforming growth factor-β. In contrast, miR-30c had little effect on extracellular matrix production but opposite effects regarding leukemia inhibitory factor and insulin-like growth factor 1. Both miRNAs indirectly affected cardiac myocytes. On transfection with pre–miR-29b, the conditioned medium of cardiac fibroblasts lost its ability to support adhesion of rat ventricular myocytes and led to a significant reduction of cardiac myocyte proteins (α-actinin, cardiac myosin-binding protein C, and cardiac troponin I). Similarly, cardiomyocytes derived from mouse embryonic stem cells atrophied under pre–miR-29 conditioned medium, whereas pre–miR-30c conditioned medium had a prohypertrophic effect. Levels of miR-29a, miR-29c, and miR-30c, but not miR-29b, were significantly reduced in a mouse model of pathological but not physiological hypertrophy. Treatment with antagomiRs to miR-29b induced excess fibrosis after aortic constriction without overt deterioration in cardiac function. Conclusions: Our proteomic analysis revealed novel molecular targets of miRNAs that are linked to a fibrogenic cardiac phenotype. Such comprehensive screening methods are essential to define the concerted actions of miRNAs in cardiovascular disease.
ON THE MENTAL NERVE AREA AND ITS RELATION TO THE GREYNESS OF HAIR
Authors: G. L. Cheatle
Journal: BMJ (1908)

liver.The necrotic transformation may be so com- plete that the centre of the tumour is of a watery or pultaceous consistence, and this may then be absorbed, le-ding to the disappearance of the tumour.In otlier cases