tbuckley/cabot-search huggingface dataset:
The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes
Authors: Louis Monnier, Claude Colette, Lawrence Leiter, Antonio Ceriello, Markolf Hanefeld, David Owens, Naoko Tajima, Jaakko Tuomiletho, Jaime Davidson
Journal: Diabetes Care (2006)

In an analysis of the datasets collected in the Diabetes Control and Complications Trial, Kilpatrick et al. (1) reported that mean blood glucose was predictive of microvascular complications in patients with type 1 diabetes, while glucose variability did not appear to be a factor in their development. We question their methodology and thereby also the conclusions. They calculated the variability of within-day blood glucose as the SD around the mean of a seven-point glycemic profile measured at each patient’s quarterly visit. With such a methodology, they have probably not selected major glucose fluctuations, but rather a composite of both major and minor fluctuations, …
Early HIV-1 Envelope-specific Cytotoxic T Lymphocyte Responses in Vertically Infected Infants
Authors: Cheryl A. Pikora, John L. Sullivan, Dennis Panicali, Katherine Luzuriaga
Journal: The Journal of Experimental Medicine (1997)

High frequencies of cytotoxic T lymphocyte precursors (CTLp) recognizing HIV-1 laboratory strain gene products have been detected in adults within weeks of primary infection. In contrast, HIV-1–specific CTLp are uncommonly detected in infants younger than 6 mo. To address the hypothesis that the use of target cells expressing laboratory strain env gene products might limit the detection of HIV-1 env-specific CTLp in early infancy, recombinant vaccinia vectors (vv) expressing HIV-1 env genes from early isolates of four vertically infected infants were generated. The frequencies of CTLp recognizing target cells infected with vv-expressing env gene products from early isolates and HIV-1 IIIB were serially measured using limiting dilution followed by in vitro stimulation with mAb to CD3. In one infant, the detection of early isolate env-specific CTLp preceded the detection of IIIB-specific CTLp. CTLp recognizing HIV-1 IIIB and infant isolate env were detected by 6 mo of age in two infants. In a fourth infant, HIV-1 IIIB env and early isolate env-specific CTLp were simultaneously detected at 12 mo of age. These results provide evidence that young infants can generate HIV-1–specific CTL responses and provide support for the concept of neonatal vaccination to prevent HIV-1 transmission. However, the early predominance of type-specific CTL detected in some young infants suggests that the use of vaccines based on laboratory strains of HIV-1 may not protect against vertical infection.
Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat
Authors: P J De Bleser, C D Scott, T Niki, G Xu, E Wisse, A Geerts
Journal: Hepatology (1996)

The liver is reported to be the main source of soluble insulin–like growth factor–II/mannose 6–phosphate (IGF–II/M6P) receptor in adults. In view of the role of this receptor in the activation of transforming growth factor β (TGF–β) during hepatic fibrogenesis, we have investigated the correlation between serum levels and tissue expression of the receptor during acute CCl4 intoxication of the rat. Sixteen hours after CCl4, injection, the level of the soluble receptor in serum, as measured by radioimmunoassay (RIA), increased threefold. At 24 hours, values almost returned to normal, but increased again by twofold at 48 hours. By 96 hours, nearly normal values were obtained. Northern blot analysis showed peaks in tissue IGF–II/M6P receptor messenger RNA (mRNA) levels at 24 hours and at 48 hours. In normal liver, immunostaining for IGF–II/M6P receptor showed weak positivity in parenchymal cells. CCl4–induced hydropic changes appeared in centrilobular parenchymal cells (PCs) at 8 hours. These changes extended to the midzonal region at 16 hours. Hydropic cells were devoid of receptor staining. The hydropic wave became extinct at 32 hours. At 48 hours, we observed a collapse of PCs in the centrilobular zone, coinciding with strongly positive staining for IGF–II/M6P receptor in fat–storing cells (FSCs), identified by dual IGF–II/M6P receptor and desmin immunostaining. Between 48 and 72 hours, the liver gradually regained its normal appearance. As shown by Western blotting, in vitro differentiated FSCs released soluble receptor in the medium. Northern blot analysis showed this release to be preceded by an increased receptor–mRNA expression, whereas immunostaining showed an increase of intracellular receptor. In conclusion, we have shown that acute CCl4 intoxication induces two peaks in serum levels of soluble receptor. While the first peak at 16 hours coincides with the loss of receptor– staining in hydropically damaged PCs, the second peak at 48 hours is paralleled by an increase in positive staining in FSCs and tissue mRNA level. Differentiated FSCs shed soluble receptor in vitro . As a consequence, these cells might contribute to the serum levels of soluble receptor in vivo . These results indicate that measuring serum soluble IGF–II/M6P receptor might useful in the diagnosis of early acute liver damage.
Targeted Overexpression of CCAAT/Enhancer-Binding Protein-δ Evokes Enhanced Gene Transcription of Platelet-Derived Growth Factor α-Receptor in Vascular Smooth Muscle Cells
Authors: Zhao-Hui Yang, Yutaka Kitami, Yasunori Takata, Takafumi Okura, Kunio Hiwada
Journal: Circulation Research (2001)

Abstract— Platelet-derived growth factor (PDGF) is thought to play a significant role in various models of vascular remodeling, particularly in the early process of vascular diseases. Its action is mediated by its specific receptor, the PDGF receptor. The PDGF α-receptor (PDGFαR) plays an important role in the growth and proliferation of vascular smooth muscle cells (VSMCs), and its gene expression is thought to be regulated by several potential transcriptional nuclear factors. However, the detailed mechanisms of tissue-specific transactivation of the PDGFαR gene in VSMCs remain to be clarified. We have previously demonstrated that the rat PDGFαR gene contains an enhancer core sequence for CCAAT/enhancer-binding proteins (C/EBPs) in its promoter region, and we have also suggested that C/EBP-δ is the principal factor involved in the induction of tissue-specific transcriptional activity of the PDGFαR gene in VSMCs. To explore the definitive roles of C/EBP-δ protein on PDGFαR gene transcription in VSMCs, we developed C/EBP-δ transgenic rats by using a chimeric fusion gene of the mouse smooth muscle α-actin promoter and an entire coding region of rat C/EBP-δ cDNA. This report describes the first successful targeted overexpression of C/EBP-δ capable of inducing PDGFαR gene transcription and modifying cell proliferative activity to PDGFs. Targeted overexpression of C/EBP-δ evokes high levels of PDGFαR gene expression, susceptibility to VSMC growth, and proliferation of VSMCs to PDGFs. The results obtained reveal evidence of a new role and new functional significance of C/EBP-δ on VSMC growth via the PDGFαR during the process of vascular remodeling and atherosclerosis.
Reversibility of diabetic cardiomyopathy with insulin in rats.
Authors: F S Fein, J E Strobeck, A Malhotra, J Scheuer, E H Sonnenblick
Journal: Circulation Research (1981)

Diabetes appears to cause a cardiomyopathy independent of atherosclerotic coronary artery disease and hypertension. Left ventricular papillary muscle function studies in rats made severely diabetic with streptozotocin have shown a slowing of relaxation and a depression of shortening velocity. However, the effects of insulin therapy on the myocardial mechanics of diabetic rats have not been studied. Therefore, rats diabetic for 6-10 weeks were treated with PZI insulin for 2, 6, 10, or 28 days and the mechanical performance of their left ventricular papillary muscles was compared to that of untreated diabetics and age-matched controls; cardiac contractile protein enzymatic activity was also measured. Neither 2 nor 6 days of therapy had any effects on the depressed cardiac muscle performance of diabetic animals, although plasma glucose concentration was restored to normal. By 10 days of therapy, recovery of mechanical performance was nearly complete, and by 28 days of therapy, complete reversal of the altered myocardial mechanics was observed. Crystalline insulin added to the bath (9 mU/ml) had no effect on myocardial mechanics in either diabetics or controls. A gradual recovery of actomyosin and myosin ATPase activity in the hearts of insulin-treated diabetic animals was also found, complementing the mechanical studies. In addition to demonstrating a gradual but complete reversibility of the abnormalities in papillary muscle function in diabetic rats (although control of hyperglycemia was less than ideal), this study confirms that this model of a cardiomyopathy is not a result of streptozotocin-induced cardiac toxicity. Additional data are provided indicating that depressed thyroid hormone levels in diabetic rats are not responsible for the mechanical changes observed.
Update in Lung Cancer and Oncological Disorders 2010
Authors: Balazs Halmos, Charles A. Powell
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Lung cancer remains the leading cause of cancer mortality in the world, with 157,000 deaths expected in the United States in 2010 (1).Despite the large death toll, there are reasons to be cautiously optimistic for a future with fewer lung cancer deaths.First, incidence and death rates are declining in U.S. men and are plateauing in women, following trends of declining smoking prevalence rates over the past 30 years (2).Second, recent studies of lung cancer screening, staging, drug development, and molecular diagnostics have demonstrated important advances that promise to decrease death rates over time (3).Third, epidemiological and bench science research have provided important insights into lung cancer susceptibility and pathogenesis.Recent advances in clinical and bench science directed toward diagnostics and therapy have had significant and often dramatic impacts on patient outcomes.These developments suggest that smoking prevention, chest computed tomography (CT) screening, and personalized approaches to treating lung cancer will significantly reduce lung cancer mortality.In this update, we present recent research findings and highlight future directions for lung cancer research and therapy.
Voltage-Sensitive Dyes and Functional Activity in the Olfactory Pathway
Authors: A R Cinelli, J S Kauer
Journal: Annual Review of Neuroscience (1992)

Many of the difficulties encountered in studying how information is handled in the CNS relate to problems with observing and characterizing activities oflarge numbers of neurons, yet it is undoubtedly the interactions between multitudes of cellular elements that underlie the complexity of processing in neuronal circuits. One of the greatest challenges facing the study of circuitry function, then, is to be able to observe the anatomical and physiological characteristics of many cells simultaneously in minute detail. The large numbers and great diversity of neurons, the segregation of processing functions within them, and the enormous complexity of their interconnections require methods that permit simultaneous observations to be made from many neuronal sites with high spatial and temporal resolution. This review summarizes results obtained with voltage-sensitive dye re­ cording, a method having good spatial and temporal resolution for observ­ ing distributed neuronal activity, as it has been applied to the olfactory pathway. Since spatially and temporally distributed activity patterns appear to be basic components of odorant encoding, the olfactory system has been useful for analyzing general mechanisms, possibly rei event to other brain regions, by which such patterns might carry information. In the present review we describe results obtained with voltage-sensitive dye
Dermatitis artefacta induced in a patient by one of her multiple personalities
Authors: WALTER B. SHELLEY
Journal: British Journal of Dermatology (1981)

Journal Article Dermatitis artefacta induced in a patient by one of her multiple personalities Get access WALTER B. SHELLEY WALTER B. SHELLEY Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue 5, 1 November 1981, Pages 587–589, https://doi.org/10.1111/j.1365-2133.1981.tb00804.x Published: 01 November 1981 Article history Accepted: 26 January 1981 Published: 01 November 1981
B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8− dendritic cells require the intramembrane endopeptidase SPPL2A
Authors: Hannes Bergmann, Mehmet Yabas, Alanna Short, Lisa Miosge, Nadine Barthel, Charis E. Teh, Carla M. Roots, Katherine R. Bull, Yogesh Jeelall, Keisuke Horikawa, Belinda Whittle, Bhavani Balakishnan, Geoff Sjollema, Edward M. Bertram, Fabienne Mackay, Andrew J. Rimmer, Richard J. Cornall, Matthew A. Field, T. Daniel Andrews, Christopher C. Goodnow, Anselm Enders
Journal: The Journal of Experimental Medicine (2012)

Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase–like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature B cell subsets, mirroring deficiency of the cytokine B cell–activating factor (BAFF). Accumulation of Sppl2a-deficient B cells was rescued by overexpression of the BAFF-induced survival protein B cell lymphoma 2 (BCL2) but not BAFF and was distinguished by low surface BAFF receptor and IgM and IgD B cell receptors. CD8-negative dendritic cells were also greatly decreased. SPPL2A deficiency blocked the proteolytic processing of CD74 MHC II invariant chain in both cell types, causing dramatic build-up of the p8 product of Cathepsin S and interfering with earlier steps in CD74 endosomal retention and processing. The findings illuminate an important role for the final step in the CD74–MHC II pathway and a new target for protease inhibitor treatment of B cell diseases.
Angiotensin II Receptor Blockade Reduces Tachycardia-Induced Atrial Adhesion Molecule Expression
Authors: Andreas Goette, Alicja Bukowska, Uwe Lendeckel, Michaela Erxleben, Matthias Hammwöhner, Denis Strugala, Jan Pfeiffenberger, Friedrich-Wilhelm Röhl, Christof Huth, Matthias P.A. Ebert, Helmut U. Klein, Christoph Röcken
Journal: Circulation (2008)

Background— Increased levels of inflammatory markers are predictors of thromboembolic events during atrial fibrillation (AF). Increased endocardial expression of adhesion molecules (ie, vascular cell adhesion molecule [VCAM] and intercellular adhesion molecule [ICAM]) could be an important link between initiation of inflammatory and prothrombogenic mechanisms responsible for thrombus development at the atrial endocardium (endocardial remodeling). Methods and Results— Tissue microarrays were used to screen right atrial tissue specimens obtained from 320 consecutive patients for differences in atrial expression of the prothrombogenic proteins VCAM-1, ICAM-1, thrombomodulin, plasminogen activator inhibitor-1, and von Willebrand factor. An in vitro organotypic human atrial tissue model and a pig model of rapid atrial pacing were used to determine the therapeutic impact of angiotensin II receptor blockade. Immunohistochemical analyses showed that all prothrombogenic proteins are expressed by endocardial cells. Using multivariable analysis, only the intensity of VCAM-1 expression was increased in patients with AF ( P =0.03). Increased atrial VCAM-1 expression was confirmed by Western blotting in patients with persistent and paroxysmal AF (persistent AF 207±42% versus sinus rhythm 100±16%, P =0.028; paroxysmal AF 193±42%, P =0.024 versus sinus rhythm). In vitro pacing of ex vivo human atrial tissue slices confirmed that rapid activation causes VCAM-1 upregulation (mRNA and protein levels). Pacing-induced VCAM-1 expression was abolished by olmesartan. To confirm this finding in vivo, VCAM-1 expression was determined in 14 pigs after rapid atrial pacing (600 bpm). Atrial tachycardia caused an upregulation of VCAM-1 expression, which was prevented by irbesartan, consistent with the observed increase in plasma levels of angiotensin II. Alterations in the in vivo VCAM-1 expression were more pronounced in the left atrium (&gt;5-fold compared with sham) than in the right atrium (3.5-fold compared with sham). Conclusions— AF and rapid atrial pacing both increase endocardial VCAM-1 expression, which can be attenuated by angiotensin II receptor blockade. This provides evidence that angiotensin II plays a pathophysiological role in prothrombotic endocardial remodeling.
Effect of implementation of Integrated Management of Neonatal and Childhood Illness (IMNCI) programme on neonatal and infant mortality: cluster randomised controlled trial
Authors: N. Bhandari, S. Mazumder, S. Taneja, H. Sommerfelt, T. A. Strand
Journal: BMJ (2012)

<b>Objective</b> To evaluate the Indian Integrated Management of Neonatal and Childhood Illness (IMNCI) programme, which integrates improved treatment of illness for children with home visits for newborn care, to inform its scale-up. <b>Design</b> Cluster randomised trial. <b>Setting</b> 18 clusters (population 1.1 million) in Haryana, India. <b>Participants</b> 29 667 births in intervention clusters and 30 813 in control clusters. <b>Intervention</b> Community health workers were trained to conduct postnatal home visits and women's group meetings; physicians, nurses, and community health workers were trained to treat or refer sick newborns and children; supply of drugs and supervision were strengthened. <b>Main outcome measures</b> Neonatal and infant mortality; newborn care practices. <b>Results</b> The infant mortality rate (adjusted hazard ratio 0.85, 95% confidence interval 0.77 to 0.94) and the neonatal mortality rate beyond the first 24 hours (adjusted hazard ratio 0.86, 0.79 to 0.95) were significantly lower in the intervention clusters than in control clusters. The adjusted hazard ratio for neonatal mortality rate was 0.91 (0.80 to 1.03). A significant interaction was found between the place of birth and the effect of the intervention for all mortality outcomes except post-neonatal mortality rate. The neonatal mortality rate was significantly lower in the intervention clusters in the subgroup born at home (adjusted hazard ratio 0.80, 0.68 to 0.93) but not in the subgroup born in a health facility (1.06, 0.91 to1.23) (P value for interaction=0.001). Optimal newborn care practices were significantly more common in the intervention clusters. <b>Conclusions</b> Implementation of the IMNCI resulted in substantial improvement in infant survival and in neonatal survival in those born at home. The IMNCI should be a part of India's strategy to achieve the millennium development goal on child survival. <b>Trial registration</b> Clinical trials NCT00474981; ICMR Clinical Trial Registry CTRI/2009/091/000715.
Strategies of muscle training in very severe COPD patients
Authors: I. Vogiatzis
Journal: European Respiratory Journal (2011)

There is strong evidence that exercise training, constituting the cornerstone of pulmonary rehabilitation, improves exercise tolerance, dyspnoea sensations, functional capacity and quality of life in patients with severe chronic obstructive pulmonary disease. However, intolerable sensations of breathlessness and/or peripheral muscle discomfort may prevent such patients from tolerating high-intensity exercise levels for sufficiently long periods of time to obtain true physiological training effects. Accordingly, the major issue that arises is the selection of the appropriate training strategy, which is tailored to the cardiovascular, pulmonary and peripheral muscle limitations of the individual patient and is aimed at maximising the effect of exercise conditioning. Within this context, the present article explores the application of strategies that optimise exercise tolerance by reducing dyspnoea sensations, namely noninvasive mechanical ventilation, oxygen and/or heliox supplementation. Administration of heliox or oxygen during exercise also increases peripheral muscle oxygen delivery, thereby delaying the onset of peripheral muscle fatigue. Particular emphasis is also given to interval exercise and resistance-muscle training as both modalities allow the application of intense loads on peripheral muscles with tolerable levels of dyspnoea sensations. In patients with profound muscle weakness and intense breathlessness upon physical exertion, execution of short bouts of interval or local muscle strength conditioning, along with oxygen breathing, may constitute a feasible and effective approach to pulmonary rehabilitation.
New Generation Cigarettes: Safety or Smoke Screen?
Authors: K. Broder
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article New Generation Cigarettes: Safety or Smoke Screen? Get access Karen Broder Karen Broder Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 2, 17 January 1990, Pages 89–91, https://doi.org/10.1093/jnci/82.2.89 Published: 17 January 1990