tbuckley/cabot-search huggingface dataset:
Cytokines as Mediators of Autoimmune Diabetes and Diabetic Complications
Authors: OLEH G. PANKEWYCZ, JING-XIN GUAN, JOHN F. BENEDICT
Journal: Endocrine Reviews (1995)

Over the last several years, there has been a considerable and rapid expansion in our understanding of the cytokines. Insights into cytokine functions gained from basic biological studies are currently being applied to the study of autoimmune diabetes. It has become clear that cytokines are critical regulating elements involved in the processes of initiating, promoting, and effecting beta-cell destruction. It is also evident that cytokine functions in IDDM are determined by timing of appearance and local synthesis, as well as the prevailing cytokine and cellular milieu. Elucidating individual cytokine responses in IDDM may offer new insights into mechanisms of disease pathogenesis and may lead to novel cytokine-based therapies for the treatment of IDDM. It may also be possible that the intensity or character of a patient's cytokine response to islet injury or to the metabolic changes inherent to diabetes may influence the ultimate expression of IDDM or its complications. Clearly, this rapidly expanding field of study should have a major impact on our understanding of diabetogenesis, our ability to intervene in our understanding of diabetogenesis, our ability to intervene in the disease process itself, and ultimately our capacity to care for individuals with IDDM.
Abstract 2503: Distinct radiosensitivities of human FancG-/- and FancD2-/- cell lines
Authors: Mark E. Bernard, Michael W. Epperly, Darcy Franicola, Xichen Zhang, Donna Shields, Frank Houghton, Christopher J. Bakkenist, Eva C. Guinan, Neeta Kannan, Joel S. Greenberger
Journal: Cancer Research (2011)

Abstract Background: Fanconi Anemia is an autosomal recessive disorder marked by a dysfunction of DNA repair, an increased sensitivity to DNA crosslinking agents, and some patients poorly tolerating ionizing irradiation. We determined the radiosensitivity of two Fanconi patient cell lines and we determined if the nitroxide radioprotector Tempo or a novel mitochondrial targeted nitroxide JP4-039 could alter their radiosensitivity. Materials and Methods: Fanconi patient derived fibroblastic cell lines, PD326 and PD20F, and their respective transgene restored cell lines FancG and FancD2 were irradiated to doses ranging from 0 to 8 Gy in the presence or absence of Tempo or JP4-039 (10 µm), plated, and colonies greater than 50 cells were counted eight days later. Results: The PD20F cell line was more radiosensitive compared to the restored FancD2 cell line (n = 1.6 + 0.2 and 10.7 + 3.1, respectively, p = 0.0423). In contrast the PD326 cell line was more radioresistant than its restored FancG cell line as seen by an increased shoulder on the survival curve (n = 8.1 + 1.4 and 2.2 + 0.3, respectively, p = 0.0174). JP4-039 but not Tempo increased radioresistance in the PD326 (n = 15.7 + 2.5, p = 0.0373), and FancG cell lines (10.2 + 2.1, p = 0.0151). Conclusions: The human Fanconi Anemia cell line PD326 is radioresistant when compared to its transgene restored FancG cell line, and this radioresistance is increased by treatment with the mitochondrial targeted nitroxide JP4-039. In contrast, PD20F is more radiosensitive when compared to its transgene restored FancD2 cell line. Testing the efficacy of JP4-039 and Tempo on mitigating the effects of mitomycin C treatment is being evaluated. Supported by 2U19A1068021-06 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2503. doi:10.1158/1538-7445.AM2011-2503
cAMP Phosphodiesterase Inhibitors Increases Nitric Oxide Production by Modulating Dimethylarginine Dimethylaminohydrolases
Authors: Soni Savai Pullamsetti, Rajkumar Savai, Martina Barbara Schaefer, Jochen Wilhelm, Hossein Ardeschir Ghofrani, Norbert Weissmann, Christian Schudt, Ingrid Fleming, Konstantin Mayer, James Leiper, Werner Seeger, Friedrich Grimminger, Ralph Theo Schermuly
Journal: Circulation (2011)

Pulmonary arterial hypertension is characterized by a progressive increase in pulmonary vascular resistance caused by endothelial dysfunction, inward vascular remodeling, and severe loss of precapillary pulmonary vessel cross-sectional area. Asymmetrical dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and its metabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) play important roles in endothelial dysfunction. We investigated whether combined phosphodiesterase (PDE) 3 and 4 inhibition ameliorates endothelial function by regulating the ADMA-DDAH axis.We investigated the effects of the PDE3/4 inhibitor tolafentrine in vitro on endothelial cell survival, proliferation, and apoptosis. Effects of tolafentrine on the endothelial nitric oxide synthase/nitric oxide pathway, DDAH expression, DDAH promoter activity, and cytokine release from endothelial cells and their subsequent influence on DDAH expression were investigated. In monocrotaline-induced pulmonary arterial hypertension in rats, the effects of inhaled tolafentrine on DDAH expression and activity were investigated. Real-time-polymerase chain reaction, immunocytochemistry, and PDE activity assays suggested high expression of PDE3 and PDE4 isoforms in endothelial cells. Treatment of endothelial cells with PDE3/4 inhibitor significantly decreased ADMA-induced apoptosis via a cAMP/PKA-dependent pathway by induction of DDAH2. Chronic nebulization of PDE3/4 inhibitor significantly attenuated monocrotaline-induced hemodynamic, gas exchange abnormalities, vascular remodeling, and right heart hypertrophy. Interestingly, PDE3/4 inhibitor treatment reduced ADMA and elevated nitric oxide/cGMP levels. Mechanistically, this could be attributed to direct modulatory effects of cAMP on the promoter region of DDAH2, which was consequently found to be increased in expression and activity. Furthermore, PDE3/4 inhibitor suppressed apoptosis in endothelial cells and increased vascularization in the lung.Combined inhibition of PDE3 and 4 regresses development of pulmonary hypertension and promotes endothelial regeneration by modulating the ADMA-DDAH axis.
Lipid Abnormalities in Insulin-dependent Diabetic Patients with Albuminuria
Authors: Pietro Vannini, Adolfo Ciavarella, Miranda Flammini, Alberto M Bargossi, Gabriele Forlani, Luigi C Borgnino, Giorgio Orsoni
Journal: Diabetes Care (1984)

The relationship between serum lipid, lipoprotein, and apolipoprotein levels and abnormalities of renal function has been investigated in 112 insulin-dependent (type I) diabetic patients. They were subdivided into three matched groups according to the amount of albuminuria: group A (albuminuria &amp;lt; 20 μg/min), group B (albuminuria between 20 and 150 μg/min; Albustix negative), and group C (albuminuria &amp;gt; 150 μg/min; Albustix positive). Twenty-one nondiabetic subjects with albuminuria above 150 μg/min but without nephrotic syndrome and/or renal failure and 77 healthy subjects were also studied. Mean total and LDL cholesterol, triglycerides, and apo B were higher, while HDL cholesterol and HDL/LDLcholesterol ratio were lower in group C than in groups A and B; the apo A/apo B ratio was lower in group C than in group A. Differences in apo B and in apo A/apo B ratio were found between groups A and B. No correlation between lipid parameters and amount of albuminuria was observed. Significant differences in lipid concentrations were also found in diabetic patients when compared with nondiabetic subjects with albuminuria and with healthy subjects. The present study confirmed previous reports of lipid disorders in insulin-dependent (type I) diabetes; however, the most important observation was the finding of albuminuria-related differences in lipid parameters in diabetic patients without renal failure. We think that the greater lipid abnormalities observed in diabetic patients with larger amounts of albuminuria might be the consequence both of impairment of glomerular permeability and of the diabetic state.
Abstract 2294: The nuclear association among ERα – PR – AIB1 is modulated by progestins and antiprogestins in experimental breast cancer
Authors: Sebastian J. Giulianelli, María A. Gorostiaga, Claudia Lanari
Journal: Cancer Research (2011)

Abstract The nuclear receptor coactivator AIB1 (SRC-3) is intimately associated with hormone action in estrogen receptor (ER)-positive breast cancer, and its overexpression has been associated with early resistance to endocrine therapy. In two models of ER+, progesterone receptor (PR)+ breast cancer, human T47D cells growing in vitro and C4-HD and C4-HI mouse mammary carcinomas maintained by syngeneic transplantations in BALB/c mice, we have shown that progestins induce a nuclear physical association between ERα and PR isoform A (PRA). We hypothesize that this interaction is necessary to induce progestin-induced cell proliferation. While both the pure antiestrogen ICI 182780 (ICI) and the antiprogestin RU486 inhibit tumor growth, only ICI blocked the ERα-PRA nuclear interaction induced by medroxyprogesterone acetate (MPA). RU486 showed an agonist-like effect stimulating the association between both receptors. The aim of this study was to investigate the interaction of ERα with PR isoform B (PRB) in both models and to evaluate the role of AIB1 in progestin-induced proliferation and in RU486-induced inhibition of cell proliferation. MPA (10nM) treatment induced an early increase in the nuclear co-localization between pSer118 ERα and pSer162 PRB in epithelial cells from the mouse model (p&amp;lt;0.001), and between total ERα with pSer162 PRB in T47D cells (p&amp;lt;0.001), as shown by confocal microscopy. By co-immunoprecipitation assays we corroborated that both PR isoforms interact with ERα in the cell nuclei. We also found that MPA increased the nuclear association of pSer294 PR and ERα with AIB1 in the murine epithelial tumor cells (p&amp;lt;0.001). These results were corroborated by co-immunoprecipitation in nuclear extracts from untreated or MPA-treated T47D cells. RU486 (10nM) induced similar ERα-PR interactions as MPA, but no association between PR and AIB1 was observed in RU486-treated cells. Our data support the hypothesis that a nuclear complex of ERα, both PR isoforms, and AIB1 mediates the proliferative effects of MPA. In addition, the results suggest that the lack of association of ERα-PR complexes with AIB1 may explain the antagonist effect of RU486 in these cells, supporting the hypothesis that the inhibitory effects of RU486 are related to genomic events. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2294. doi:10.1158/1538-7445.AM2011-2294
RNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells
Authors: Vasanth Vedantham, Giselle Galang, Melissa Evangelista, Rahul C. Deo, Deepak Srivastava
Journal: Circulation Research (2015)

Treatment of sinus node disease with regenerative or cell-based therapies will require a detailed understanding of gene regulatory networks in cardiac pacemaker cells (PCs).To characterize the transcriptome of PCs using RNA sequencing and to identify transcriptional networks responsible for PC gene expression.We used laser capture microdissection on a sinus node reporter mouse line to isolate RNA from PCs for RNA sequencing. Differential expression and network analysis identified novel sinoatrial node-enriched genes and predicted that the transcription factor Islet-1 is active in developing PCs. RNA sequencing on sinoatrial node tissue lacking Islet-1 established that Islet-1 is an important transcriptional regulator within the developing sinoatrial node.(1) The PC transcriptome diverges sharply from other cardiomyocytes; (2) Islet-1 is a positive transcriptional regulator of the PC gene expression program.
Infusion of Chlorothiazide in a Patient With Primary Aldosteronism
Authors: Richard A. Schacht
Journal: JAMA (1967)

An abnormally elevated rate of potassium clearance occurred in a patient with primary aldosteronism after the intravenous administration of 500 mg of chlorothiazide sodium. The infusion of chlorothiazide may have some value as a screening test for the detection of patients with aldosteronism.
Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index: a prospective, multicenter GITMO study
Authors: Roberto Raimondi, Alberto Tosetto, Rosi Oneto, Riccardo Cavazzina, Francesco Rodeghiero, Andrea Bacigalupo, Renato Fanin, Alessandro Rambaldi, Alberto Bosi
Journal: Blood (2012)
Shall The Journal be Removed to Washington?
Authors: R. Harvey Reed
Journal: JAMA (1891)

<h3>To the Editor:</h3> —I have within the last week or ten days received two or three letters suggesting that the question of removingThe Journalshould be referred back to the Trustees, who have the power to act. And now comes the deponent, the<i>St. Louis Clinique</i>of February, 1891, who deposes and says, that "<i>we hope a motion will prevail to refer the question</i>back to the trustees." But he preludes that assertion by saying that "the Board was given full power to act: by its actThe Journalwas located in Chicago, and by its authority it could remain or be removed." Very good. But will the said deponent tell the Court, who gave said Board this authority? And tell us whether the same body which extended the power in the first place, cannot rescind that power, or take up any subject referred to the Board of Trustees,
LEFT VENTRICULAR NON-COMPACTION AND LONG-TERM CARDIOVASCULAR OUTCOMES: ANALYSIS OF 769 PATIENTS BY CARDIAC MAGNETIC RESONANCE
Authors: Geetha P. Bhumireddy, Nikolas Krishna, Shahzad Zia, Nripen Dontineni, Shaun Madhar, Michael Sood, Joshua Socolow, Igor Klem, Terrence Sacchi, John Heitner
Journal: Journal of the American College of Cardiology (2012)
Use of blockers during surgery may have caused 10 000 deaths in the UK
Authors: N. Hawkes
Journal: BMJ (2013)

Up to 10 000 deaths may have been caused in the United Kingdom by following a guideline that can no longer be relied upon, says an analysis by a group from Imperial College in London.

Writing in Heart online, the group said that a guideline recommending the use of β blockers to protect the heart during non-cardiac surgery relied heavily on results from a trial led by a now discredited Dutch researcher, Don Poldermans.1 To make matters worse, Poldermans also chaired the committee that wrote the guideline.

Darrel Francis and colleagues said that there was no proof …
Opiates for Pain: Patients' Tolerance and Society's Intolerance
Authors: Alan I. Trachtenberg
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The cloning of the μ opioid receptor is a breakthrough. It is unfortunate that the Medical News and Perspectives<sup>1</sup>report on this contains misinformation about the use of opiates in the treatment of chronic pain. Unfortunate emphasis is given to the "possibility of finding a powerful analgesic that does not become so quickly tolerated by the body as does morphine, which could bring pain relief to people who suffer from chronic pain, patients who are not normally given morphine because of the problems of tolerance." This is not especially tantalizing to those of us familiar with the clinical treatment of (and literature on) chronic pain and drug dependence. Tolerance and physical dependence should not be barriers to use of opioids in the treatment of chronic pain.<sup>2,3</sup> The reason that patients with chronic pain are not given opiates when indicated is not tolerance but rather the
Topical 5-aminolaevulinic acid photodynamic therapy for the treatment of skin conditions other than non-melanoma skin cancer
Authors: S.H. Ibbotson
Journal: British Journal of Dermatology (2002)

Summary Topical 5‐aminolaevulinic acid (ALA) photodynamic therapy (PDT) is used increasingly for superficial non‐melanoma skin cancer (NMSC) and dysplasia. However, the relative accumulation of the photosensitizer protoporphyrin IX (PpIX) in diseased tissue is not specific for neoplastic disease, and has been shown after the application of ALA to benign proliferative skin conditions such as viral warts and psoriasis. This review appraises the quality of evidence available for the use of topical ALA–PDT in the treatment of skin conditions other than NMSC. The diseases that have been studied in most detail are recalcitrant viral warts, acne, psoriasis and cutaneous T‐cell lymphoma. Publications relating to the treatment of other diseases by topical PDT are restricted to small case series or case reports. The relevant literature will be discussed and the potential for topical PDT in the treatment of several skin diseases is highlighted, although more detailed studies are required to clarify the role of PDT beyond the treatment of NMSC.
Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo
Authors: Claire M. Edwards, James R. Edwards, Seint T. Lwin, Javier Esparza, Babatunde O. Oyajobi, Brandon McCluskey, Steven Munoz, Barry Grubbs, Gregory R. Mundy
Journal: Blood (2007)
Adaptation to metals in widespread and endemic plants.
Authors: A J Shaw
Journal: Environmental Health Perspectives (1994)

Bryophytes, including the mosses, liverworts, and hornworts, occur in a variety of habitats with high concentrations of metals and have other characteristics that are advantageous for studies of metal tolerance. Mosses may evolve genetically specialized, metal-tolerant races less frequently than flowering plants. Some species of mosses appear to have inherently high levels of metal tolerance even in individuals that have not been subjected to natural selection in contaminated environments. Scopelophila cataractae, one of the so-called copper mosses, not only tolerates extremely high concentrations of metals in its substrates, but requires these substrates for optimum growth. This species should be included in mechanistic studies of tolerance at the cellular and molecular levels.
Abstract P3-02-01: Pregnancy-associated plasma protein A regulates mitosis and is epigenetically silenced in breast cancer
Authors: R Sainsbury, M Loddo, J Andryszkiewicz, M Widschwendter, K Stoeber, G Williams
Journal: Cancer Research (2013)

Abstract Using Phosphohistone-H3, a marker of cells in mitosis, we identified mitotic delay in 95% of invasive breast cancers with a significant proportion of cells in prophase/prometaphase (58%). This delay was seen in breast cancer tissues only with other malignancies and normal tissues showing a normal mitotic phase distribution (23% of mitotic cells in prophase/prometaphase). We could detect a clear mitotic delay phenotype already in 80% (55 out of 69 evaluable patients) of precursor ductal carcinoma in situ (DCIS) lesions. This strong phenotype has been concealed for over a century because tinctorial stains routinely used in diagnostic practice do not allow cells in prophase or prometaphase to be distinguished from interphase cells. Promoter methylation analysis of candidate genes linked this defect to epigenetic silencing of the gene encoding Pregnancy-Associated Plasma Protein-A (PAPPA), a secreted protease. PAPPA silencing was highly prevalent in precursor lesions and invasive breast cancer. Experimental manipulation of PAPPA protein levels in human mammary epithelial cells and in breast cancer cell lines demonstrates that progression through early mitosis is dependent on PAPPA function, and that breast cancer cells become more invasive after PAPPA down regulation. We discovered that PAPPA regulates mitotic progression through its known role in modulating the IGF-1 signalling pathway, resulting in activation of the forkhead transcription factor FoxM1 which drives a transcriptional cluster of essential mitotic genes. Our results identify PAPPA as a candidate tumour suppressor in breast cancer. PAPPA loss is an early event in breast tumourigenesis increasing tumour cell invasiveness and may contribute to the transition from precursor lesions to invasive disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-02-01.
“The Days of Giants”
Authors: Henry L. Mencken
Journal: Annals of Internal Medicine (1997)

Editorials15 October 1997“The Days of Giants”Henry L. MenckenHenry L. MenckenAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-8_Part_1-199710150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Every schoolboy, I suppose, has heard by this time of Dr. [Oliver Wendell] Holmes' famous address before the Massachusetts Medical Society on May 30, 1860, in which he argued that “if the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind-and all the worse for the fishes”; but what the pedagogues always fail to tell their poor dupes is that he made a categorical exception of wine, which he ranked with opium, quinine, anesthetics and mercury among the sovereign and invaluable boons to humanity.Henry L. ... Author, Article, and Disclosure InformationAuthors: Henry L. Mencken PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1997Volume 127, Issue 8_Part_1Page: 647 ePublished: 15 August 2000 Issue Published: 15 October 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Points: Predicting intrauterine growth retardation
Authors: A T Letchworth, I. Diamond
Journal: BMJ (1987)

Professor D C Carter (7 March, p 593) com- ments on the treatment of hepatic metastases by surgical debulking, but the value of hepatic arterial embolisation is not mentioned.'2In our experience, when vascular endocrine metastases are detected in the liver, providing that the intrahepatic portal veins are patent, hepatic arterial embolisation can provide
The Interdependence of Behavior and the Psychosomatic Symptom
Authors: Peter Moldenhauer
Journal: Psychotherapy and Psychosomatics (1974)

Describing a phase in the therapeutic process of a psychosomatic patient with a borderline ego structure the author exemplifies the analogous function of somatic syndromes and acting-out in groups. Both are based on a deficitary ego, organized as a False Self. The weak ego gets supported and compensated both by the specific behavior pattern as well as the somatic symptom. In this case study an additional treatment of the somatic symptom led to a psychotic reaction, which was followed by increased acting-out. Somatic syndrome and acting-out behavior are interpreted as means of depersonalized communication and as an attempt to delimitate the ego in regard to a group which is in transference experienced as the mother. The conserving function of acting-out for the ego should be considered in respect to the selection of the therapeutic technique.