tbuckley/cabot-search huggingface dataset:
Pleiotrophin mediates hematopoietic regeneration via activation of RAS
Authors: Heather A. Himburg, Xiao Yan, Phuong L. Doan, Mamle Quarmyne, Eva Micewicz, William McBride, Nelson J. Chao, Dennis J. Slamon, John P. Chute
Journal: Journal of Clinical Investigation (2014)

Hematopoietic stem cells (HSCs) are highly susceptible to ionizing radiation-mediated death via induction of ROS, DNA double-strand breaks, and apoptotic pathways. The development of therapeutics capable of mitigating ionizing radiation-induced hematopoietic toxicity could benefit both victims of acute radiation sickness and patients undergoing hematopoietic cell transplantation. Unfortunately, therapies capable of accelerating hematopoietic reconstitution following lethal radiation exposure have remained elusive. Here, we found that systemic administration of pleiotrophin (PTN), a protein that is secreted by BM-derived endothelial cells, substantially increased the survival of mice following radiation exposure and after myeloablative BM transplantation. In both models, PTN increased survival by accelerating the recovery of BM hematopoietic stem and progenitor cells in vivo. PTN treatment promoted HSC regeneration via activation of the RAS pathway in mice that expressed protein tyrosine phosphatase receptor-zeta (PTPRZ), whereas PTN treatment did not induce RAS signaling in PTPRZ-deficient mice, suggesting that PTN-mediated activation of RAS was dependent upon signaling through PTPRZ. PTN strongly inhibited HSC cycling following irradiation, whereas RAS inhibition abrogated PTN-mediated induction of HSC quiescence, blocked PTN-mediated recovery of hematopoietic stem and progenitor cells, and abolished PTN-mediated survival of irradiated mice. These studies demonstrate the therapeutic potential of PTN to improve survival after myeloablation and suggest that PTN-mediated hematopoietic regeneration occurs in a RAS-dependent manner.
Defining polycystic ovary syndrome
Authors: A. Balen, R. Homburg, S. Franks
Journal: BMJ (2009)

New criteria say that hyperandrogenism and ovarian dysfunction are needed

Polycystic ovary syndrome (PCOS) is a well recognised and common condition that causes considerable morbidity. It comprises a group of signs and symptoms, and several attempts have been made to reach consensus on its definition. The latest proposed definition comes from a new group, the Androgen Excess and PCOS Society, which has reviewed the literature on the defining features of the syndrome.1

The original case series described seven women who had enlarged polycystic ovaries and amenorrhoea.2 The cardinal symptoms were subsequently recognised to be chronic anovulation (oligomenorrhoea or amenorrhoea) and hyperandrogenism (usually hirsutism, acne, and sometimes alopecia). These symptoms were combined in a definition produced by a consensus agreement supported by the US National Institutes of Health.3 In Europe and Australasia, ovarian imaging by ultrasound became an important component in the diagnosis, largely because ovarian morphology was part of the original description of the disease. To gain transatlantic harmony, the European …
An integrated framework for finite-element modeling of mitral valve biomechanics from medical images: Application to MitralClip intervention planning
Authors: Tommaso Mansi, Ingmar Voigt, Bogdan Georgescu, Xudong Zheng, Etienne Assoumou Mengue, Michael Hackl, Razvan I. Ionasec, Thilo Noack, Joerg Seeburger, Dorin Comaniciu
Journal: Medical Image Analysis (2012)
Acute Adverse Effects of Fine Particulate Air Pollution on Ventricular Repolarization
Authors: Duanping Liao, Michele L. Shaffer, Sol Rodriguez-Colon, Fan He, Xian Li, Deborah L. Wolbrette, Jeff Yanosky, Wayne E. Cascio
Journal: Environmental Health Perspectives (2010)

The mechanisms for the relationship between particulate pollution and cardiac disease are not fully understood.We examined the effects and time course of exposure to fine particulate matter < or = 2.5 microm in aerodynamic diameter (PM(2.5)) on ventricular repolarization of 106 nonsmoking adults who were living in communities in central Pennsylvania.The 24-hr beat-to-beat electrocardiogram (ECG) data were obtained using a high-resolution 12-lead Holter system. After visually identifying and removing artifacts and arrhythmic beats, we summarized normal beat-to-beat QTs from each 30-min segment as heart rate (HR)-corrected QT measures: QT prolongation index (QTI), Bazett's HR-corrected QT (QTcB), and Fridericia's HR-corrected QT (QTcF). A personal PM(2.5) monitor was used to measure individual-level real-time PM(2.5) exposures for 24 hr. We averaged these data and used 30-min time-specific average PM(2.5) exposures.The mean age of the participants was 56 +/- 8 years, with 41% male and 74% white. The means +/- SDs for QTI, QTcB, and QTcF were 111 +/- 6.6, 438 +/- 23 msec, and 422 +/- 22 msec, respectively; and for PM(2.5), the mean +/- SD was 14 +/- 22 microg/m3. We used distributed lag models under a framework of linear mixed-effects models to assess the autocorrelation-corrected regression coefficients (beta) between 30-min PM(2.5) and the HR-corrected QT measures. Most of the adverse ventricular repolarization effects from PM(2.5) exposure occurred within 3-4 hr. The multivariable adjusted beta (SE, p-value) due to a 10-microg/m3 increase in lag 7 PM(2.5) on QTI, QTcB, and QTcF were 0.08 (0.04, p < 0.05), 0.22 (0.08, p < 0.01), and 0.09 (0.05, p < 0.05), respectively.Our results suggest a significant adverse effect of PM(2.5) on ventricular repolarization. The time course of the effect is within 3-4 hr of elevated PM(2.5).
Patients with early inflammatory arthritis who fulfil the 2010 American College of Rheumatology–European League Against Rheumatism classification criteria for rheumatoid arthritis have increased mortality compared with those who do not: results from the Norfolk Arthritis Register
Authors: JH Humphreys, SMM Verstappen, M Lunt, J Chipping, KL Hyrich, T Marshall, DPM Symmons
Journal: The Lancet (2013)
An Experimental Investigation OF THE SUITABILITY OF THE MORE SOLUBLE SALTS OF QUININE AND CINCHONINE FOR INTRAVENOUS INJECTION
Authors: L. Rogers
Journal: BMJ (1917)

QUININE AND CINCHONINE SALTg.rmDTouclmAru 3u of the minute filterable virus frequently to be found in meningococcal cultures makes it impossible to be certain that in picking up a normal sized meningococcus one is not at the same time picking up some of this filterable yirus.And this objection also applies to the presence of Nil Nil Nil.C = Complete agglutination.P = Partial agglutination.
IFN-γ Mediates the Rejection of Haematopoietic Stem Cells in IFN-γR1-Deficient Hosts
Authors: Martin Rottman, Claire Soudais, Guillaume Vogt, Laurent Renia, Jean-François Emile, Hélène Decaluwe, Jean-Louis Gaillard, Jean-Laurent Casanova
Journal: PLoS Medicine (2008)

Interferon-gamma receptor 1 (IFN-gammaR1) deficiency is a life-threatening inherited disorder, conferring predisposition to mycobacterial diseases. Haematopoietic stem cell transplantation (HSCT) is the only curative treatment available, but is hampered by a very high rate of graft rejection, even with intra-familial HLA-identical transplants. This high rejection rate is not seen in any other congenital disorders and remains unexplained. We studied the underlying mechanism in a mouse model of HSCT for IFN-gammaR1 deficiency.We demonstrated that HSCT with cells from a syngenic C57BL/6 Ifngr1+/+ donor engrafted well and restored anti-mycobacterial immunity in naive, non-infected C57BL/6 Ifngr1-/- recipients. However, Ifngr1-/- mice previously infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) rejected HSCT. Like infected IFN-gammaR1-deficient humans, infected Ifngr1-/- mice displayed very high serum IFN-gamma levels before HSCT. The administration of a recombinant IFN-gamma-expressing AAV vector to Ifngr1-/- naive recipients also resulted in HSCT graft rejection. Transplantation was successful in Ifngr1-/- x Ifng-/- double-mutant mice, even after BCG infection. Finally, efficient antibody-mediated IFN-gamma depletion in infected Ifngr1-/- mice in vivo allowed subsequent engraftment.High serum IFN-gamma concentration is both necessary and sufficient for graft rejection in IFN-gammaR1-deficient mice, inhibiting the development of heterologous, IFN-gammaR1-expressing, haematopoietic cell lineages. These results confirm that IFN-gamma is an anti-haematopoietic cytokine in vivo. They also pave the way for HSCT management in IFN-gammaR1-deficient patients through IFN-gamma depletion from the blood. They further raise the possibility that depleting IFN-gamma may improve engraftment in other settings, such as HSCT from a haplo-identical or unrelated donor.
Bilateral cavernous sinus thrombosis complicating sinusitis
Authors: M Absoud, F Hikmet, P Dey, M Joffe, E Thambapillai
Journal: Journal of the Royal Society of Medicine (2006)

Cavernous sinus thrombosis is a rare yet potentially fatal and debilitating condition in children which is important to diagnose early. It requires a high index of suspicion and confirmation by imaging.
Phosphodiesterase Type 5
Authors: David A. Kass, Hunter C. Champion, Joseph A. Beavo
Journal: Circulation Research (2007)

Phosphodiesterase type 5A (PDE5A) selectively hydrolyzes cyclic GMP. Inhibitors of PDE5A such as sildenafil are widely used to treat erectile dysfunction, but growing evidence supports important roles for the enzyme in both the vasculature and heart. In disorders such as cardiac failure, PDE5A upregulation may contribute to a decline in cGMP and protein kinase G signaling, exacerbating dysfunction. PDE5A plays an important role in the pulmonary vasculature where its inhibition benefits patients with pulmonary hypertension. In the heart, PDE5A signaling appears compartmentalized, and its inhibition is cardioprotective against ischemia-reperfusion and antracycline toxicity, blunts acute adrenergic contractile stimulation, and can suppress chronic hypertrophy and dysfunction attributable to pressure-overload. In this review, we discuss the molecular biology, pharmacology, and physiology of PDE5A, mechanisms of vascular and cardiac regulation, and recent evidence supporting the utility of selective PDE5A inhibition for the treatment of cardiovascular disorders.
Ethics expert advocates payment for organ donors
Authors: David Spurgeon
Journal: BMJ (2006)

Ethical and philosophical arguments against the sale of organs for transplantation are difficult to sustain when scrutinised closely, says a University of Toronto professor of public health and surgery in an article entitled “The case for a regulated system of living kidney sales” ( Nature Clinical Practice Nephrology 2006;2:600-1).

Abdallah Daar, director of ethics and policy for the McLaughlin Centre for Molecular Medicine and co-director of the Canadian Program on Genomics and Global Health, says he and colleagues in the International Forum for Transplant Ethics do not argue that organ sales are always acceptable or that …
Continuous Intragastric Milk Feeds in Infants of Low Birth Weight
Authors: H. B. Valman, C. D. Heath, R. J. K. Brown
Journal: BMJ (1972)

In a feeding trial 66 infants of low birth weight received continuous intragastric milk feeds from the fourth hour of life, starting with 60 ml/kg/24 hr and reaching a maximum of 300 ml/kg/24 hr on the ninth day. Each infant received only full-strength milk, which was either expressed human breast milk or SMA-S26 (a proprietary low-protein adapted cows9 milk) or half-cream Regal milk (partly-skimmed evaporated cows9 milk). For various reasons 10 babies had to be withdrawn, and the final assessment was made on the 56 who completed the trial successfully. Persistent vomiting was a problem in only four infants. In two of them the trial was continued after gastric lavage and in the other two vomiting stopped when the volume was reduced. Despite a careful search no evidence was found of aspiration of feeds in any infant. Continuous intragastric milk infusion was shown to be a safe method of feeding infants of low birth weight and SMA-S26 was almost as well tolerated as human milk. Because of the high-protein content of half-cream cows9 milk preparations and the resultant high plasma amino-acid levels when they are given in these large volumes they should be avoided for this type of feeding although they produce better weight gains in the first week of life.
NCCTG N0821 (Alliance): A Phase II First-Line Study of Pemetrexed, Carboplatin, and Bevacizumab in Elderly Patients with Advanced Nonsquamous Non–Small-Cell Lung Cancer With Good Performance Status
Authors: Grace K. Dy, Julian R. Molina, Yingwei Qi, Rafat Ansari, Sachdev Thomas, Helen J. Ross, Gamini Soori, Daniel Anderson, Marie Christine Aubry, Jeffrey Meyers, Araba A. Adjei, Sumithra Mandrekar, Alex A. Adjei
Journal: Journal of Thoracic Oncology (2014)
Prognosis in patients with recent onset low back pain in Australian primary care: inception cohort study
Authors: N. Henschke, C. G Maher, K. M Refshauge, R. D Herbert, R. G Cumming, J. Bleasel, J. York, A. Das, J. H McAuley
Journal: BMJ (2008)

<b>Objective</b> To estimate the one year prognosis and identify prognostic factors in cases of recent onset low back pain managed in primary care. <b>Design</b> Cohort study with one year follow-up. <b>Setting</b> Primary care clinics in Sydney, Australia. <b>Participants</b> An inception cohort of 973 consecutive primary care patients (mean age 43.3, 54.8% men) with non-specific low back pain of less than two weeks’ duration recruited from the clinics of 170 general practitioners, physiotherapists, and chiropractors. <b>Main outcome measures</b> Participants completed a baseline questionnaire and were contacted six weeks, three months, and 12 months after the initial consultation. Recovery was assessed in terms of return to work, return to function, and resolution of pain. The association between potential prognostic factors and time to recovery was modelled with Cox regression. <b>Results</b> The follow-up rate over the 12 months was more than 97%. Half of those who reduced their work status at baseline had returned to previous work status within 14 days (95% confidence interval 11 to 17 days) and 83% had returned to previous work status by three months. Disability (median recovery time 31 days, 25 to 37 days) and pain (median 58 days, 52 to 63 days) took much longer to resolve. Only 72% of participants had completely recovered 12 months after the baseline consultation. Older age, compensation cases, higher pain intensity, longer duration of low back pain before consultation, more days of reduced activity because of lower back pain before consultation, feelings of depression, and a perceived risk of persistence were each associated with a longer time to recovery. <b>Conclusions</b> In this cohort of patients with acute low back pain in primary care, prognosis was not as favourable as claimed in clinical practice guidelines. Recovery was slow for most patients. Nearly a third of patients did not recover from the presenting episode within a year.
Mortality associated with passive smoking in Hong Kong
Authors: S M McGhee, S Y Ho, M Schooling, L M Ho, G N Thomas, A J Hedley, K H Mak, R Peto, T H Lam
Journal: BMJ (2005)

Passive smoking can cause death from lung cancer and coronary heart disease, but there is little evidence for associations with other causes of death in never smokers.A recent study showed increased all cause mortality with exposure to secondhand smoke at home but did not examine associations with specific causes of death and dose-response relations. 1 We have published estimates of the mortality attributable to active smoking in Hong Kong 2 and now present the related findings on passive smoking at home.
<i>Juan de Pareja</i>
Authors: Thomas B. Cole
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Severe adverse reactions prompt call for trial design changes
Authors: Susan Mayor
Journal: BMJ (2006)

Drugs from new chemical or biological classes being tested in phase I trials—the earliest trials of a new drug in humans—should be tested in only one person at a time, a specialist said after a UK phase I trial resulted in six healthy volunteers becoming severely ill.

The young men were taking part in the first study in humans of TGN1412, a fully humanised monoclonal antibody designed to bind to CD28, a cell surface molecule on T cells which play a role in a variety of cell mediated immune reactions. The drug was being developed for the treatment of autoimmune and inflammatory diseases and leukaemia by a German company, TeGenero.

The six volunteers developed severe reactions within three hours of being given TGN1412 intravenously, while two other men who were given a placebo showed no sign of illness. One of those who was given the placebo told the BBC that the men who became ill reported feeling cold before developing severe headache and swelling of the head and neck. They later developed multiple organ failure and needed intensive care.

Ganesh Suntharalingam, clinical director of intensive care at Northwick Park …
Sodium ionophore converts growth manner of vascular smooth muscle cells from spontaneously hypertensive rats
Authors: T. Osanai, T. Kanazawa, T. Okuguchi, T. Kamada, H. Metoki, Y. Oike, K. Onodera
Journal: Cardiovascular Research (1996)

Vasoconstrictor peptides such as endothelin (ET) cause hypertrophy of vascular smooth muscle cells (VSMC) in Wistar Kyoto rats (WKY) and hyperplasia in spontaneously hypertensive rats (SHR). They also induce an increase in Na+ concentration ([Na+]i) and activate protein kinase C (PKC) independently. Therefore, we tested the hypothesis that the increase in [Na+]i may be involved in the conversion of growth manner under activated PKC in SHR VSMC.10(-7) M phorbol ester (TPA) increased the diameter and protein content of VSMC from both strains under 18% serum conditions. Further addition of 10(-6) M gramicidin (Na+ ionophore) converted TPA-induced hypertrophy to hyperplasia, which was due to the quick transition from S to G2/M phase, only in SHR VSMC. Western blot analysis showed that serum- and TPA-induced tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was potentiated by 10(-6) M gramicidin in SHR. [Na+]i, which was measured by sodium-binding benzofuran isophthalate (SBFI), was increased about 35 mM by 10(-6) M gramicidin in both strains, but TPA did not affect basal [Na+]i and the gramicidin-induced increase in [Na+]i.We conclude that sodium ionophore may convert hypertrophy to hyperplasia synergistically with activated PKC in SHR VSMC, possibly by MAP kinase phosphorylation.
Induction of Mitochondrial Biogenesis Is a Maladaptive Mechanism in Mitochondrial Cardiomyopathies
Authors: Mariangela Sebastiani, Carla Giordano, Chiara Nediani, Claudia Travaglini, Elisabetta Borchi, Massimo Zani, Mariano Feccia, Massimiliano Mancini, Vincenzo Petrozza, Andrea Cossarizza, Pietro Gallo, Robert W. Taylor, Giulia d’Amati
Journal: Journal of the American College of Cardiology (2007)
Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis.
Authors: T Abe, K Okamura, M Ono, K Kohno, T Mori, S Hori, M Kuwano
Journal: Journal of Clinical Investigation (1993)

We have developed two different models of tumor angiogenesis by human brain tumors: one being tube formation by bovine aortic endothelial (BAE) cells cocultured with tumor cells in vitro, and other being in vivo angiogenesis in mice when tumor cells are transplanted into the dorsal sac. We investigated whether tube formation could be induced in BAE cells in type I collagen gel when these cells were cocultured with seven human glioma cell lines. Four of the seven glioma cell lines, which had high levels of basic fibroblast growth factor (bFGF) mRNA, induced tube formation by BAE cells. The tube formation was blocked by coadministration of anti-bFGF antibody. In in vivo model system of tumor angiogenesis in mice, these four cell lines were highly angiogenic. In contrast, with the other three glioma cell lines, which had poor expression of bFGF, BAE cells showed no apparent tube formation. These three cell lines did not efficiently develop capillary networks in mice. The results demonstrated a correlative relationship in the tubulogenesis of BAE cells, bFGF mRNA levels and angiogenesis in mice. The present study with two model systems of tumor angiogenesis suggests that the angiogenesis of some human glioma cell lines is mediated by bFGF, possibly via paracrine control.
Abstract 3313: Snail and slug-mediated epithelial mesenchymal transition in lung cancer cells
Authors: Tamura Daisuke, Tokuzo Arao Arao, Tomoyuki Nagai Nagai, Keiichi Aomatsu, Kazuko Sakai, Kanae Kudo, Hiroyasu Kaneda, Kazuko Matsumoto, Kazuyuki Furuta, Yoshihiko Fujita, Yoshikazu Kotani, Yoshihiro Nishimura, Nagahiro Saijo, Kazuto Nishio
Journal: Cancer Research (2010)

Abstract Epithelial-Mesenchymal Transition (EMT) has been classified as a unique process by which epithelial cells undergo remarkable morphologic changes characterized by a transition from epithelial cobblestone phenotype to elongated fibroblastic phenotype (mesenchymal phenotype) leading to increased motility and invasion. Accumulating evidence indicates that EMT-inducible transcription factors such as Snail homologues (Snail1, 2, and 3) and several basic helix-loop-helix factors Twist, are poor prognostic factors and associated with chemoresistance in oncology. The aim of this study was to investigate the involvement of SNAI-mediated EMT and its malignant potential in lung cancer cells. We introduced SNAI1 or SNAI2 gene into A549 or PC-9 lung cancer cell lines and established stable cell lines A549/GFP, /SNAI1, /SNAI2, PC-9/GFP, /SNAI1 and /SNAI2. Overexpression of SNAI1 and SNAI2 clearly mediated the EMT-related morphological changes including the cell scattering and the elongation of cell-shape. Real-time RT PCR demonstrated that overexpression of SNAI1 and SNAI2 markedly down-regulated the mRNA levels of E-cadherin about 1/2 to 1/100 compared with GFP-expressing control cell lines. The mRNA upregulation of N-cadherin, fibronectin 1 and Vimentin, which changes are characteristic of EMT, were also observed. We are now investigating its oncogenic properties, gene expression changes by microarray analysis and chemoresistance using these stable SNAI1 or SNAI2 transfectants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3313.