tbuckley/cabot-search huggingface dataset:
Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting
Authors: Maria Wirzenius, Tuomas Tammela, Marko Uutela, Yulong He, Teresa Odorisio, Giovanna Zambruno, Janice A. Nagy, Harold F. Dvorak, Seppo Ylä-Herttuala, Masabumi Shibuya, Kari Alitalo
Journal: The Journal of Experimental Medicine (2007)

Lymphatic vessel growth, or lymphangiogenesis, is regulated by vascular endothelial growth factor-C (VEGF-C) and -D via VEGF receptor 3 (VEGFR-3). Recent studies suggest that VEGF, which does not bind to VEGFR-3, can also induce lymphangiogenesis through unknown mechanisms. To dissect the receptor pathway that triggers VEGFR-3–independent lymphangiogenesis, we used both transgenic and adenoviral overexpression of placenta growth factor (PlGF) and VEGF-E, which are specific activators of VEGFR-1 and -2, respectively. Unlike PlGF, VEGF-E induced circumferential lymphatic vessel hyperplasia, but essentially no new vessel sprouting, when transduced into mouse skin via adenoviral vectors. This effect was not inhibited by blocking VEGF-C and -D. Postnatal lymphatic hyperplasia, without increased density of lymphatic vessels, was also detected in transgenic mice expressing VEGF-E in the skin, but not in mice expressing PlGF. Surprisingly, VEGF-E induced lymphatic hyperplasia postnatally, and it did not rescue the loss of lymphatic vessels in transgenic embryos where VEGF-C and VEGF-D were blocked. Our data suggests that VEGFR-2 signals promote lymphatic vessel enlargement, but unlike in the blood vessels, are not involved in vessel sprouting to generate new lymphatic vessels in vivo.
Prognostic Validation of the International Classification of Immunoglobulin M Gammopathies: A Survival Advantage for Patients with Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance?
Authors: Paolo G. Gobbi, Luca Baldini, Chiara Broglia, Maria Goldaniga, Mario Comelli, Pierre Morel, Enrica Morra, Sergio Cortelazzo, Roberto Bettini, Giampaolo Merlini
Journal: Clinical Cancer Research (2005)

To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002).A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenstrom's macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and sex and over an equivalent period of follow-up (standardized mortality ratio, SMR).IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations.Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.
Response to Letter Regarding Article, “Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction”
Authors: Dirk Westermann, Mario Kasner, Frank Spillmann, Alexander Riad, Wolfgang Poller, Matthias Pauschinger, Heinz-Peter Schultheiss, Carsten Tschöpe, Paul Steendijk, Kerstin Weitmann, Wolfgang Hoffmann
Journal: Circulation (2009)
Opportunities for New Drug Development in Psychiatry
Authors: Patricio O’Donnell, Michael D. Ehlers
Journal: JAMA Psychiatry (2015)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Human bactericidal/permeability-increasing protein and a recombinant NH2-terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria.
Authors: J Weiss, P Elsbach, C Shu, J Castillo, L Grinna, A Horwitz, G Theofan
Journal: Journal of Clinical Investigation (1992)

The bactericidal/permeability-increasing protein (BPI) of neutrophils and BPI fragments neutralize the effects of isolated Gram-negative bacterial lipopolysaccharides both in vitro and in vivo. Since endotoxin most commonly enters the host as constituents of invading Gram-negative bacteria, we raised the question: Can BPI and its bioactive fragments also protect against whole bacteria? To determine whether the bactericidal and endotoxin-neutralizing activities of BPI/fragments are expressed when Gram-negative bacteria are introduced to the complex environment of whole blood we examined the effects of added BPI and proteolytically prepared and recombinant NH2-terminal fragments on: (a) the fate of serum-resistant encapsulated Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa that survive the antibacterial actions of whole blood and (b) the ability of these bacteria to trigger cytokine release. Added BPI in nanomolar concentrations killed each of three encapsulated strains of E. coli and in closely parallel fashion inhibited tumor necrosis factor (TNF) release. Holo-BPI and its NH2-terminal fragment were equipotent toward a rough LPS chemotype K1-encapsulated strain, but the fragment was substantially more potent than holo-BPI toward two encapsulated smooth LPS chemotype strains. TNF release induced by K. pneumoniae and P. aeruginosa was also inhibited by both holo-BPI and fragment but, at the protein concentrations tested, P. aeruginosa was killed only by the fragment and K. pneumoniae was not killed by either protein. The bactericidal action of BPI/fragment toward E. coli is inhibited by C7-depleted serum, but accelerated by normal serum, indicating that BPI, acting in synergy with late complement components, enhances extracellular killing of serum-resistant bacteria. Thus, BPI and an even more potent NH2-terminal fragment may protect against Gram-negative bacteria in the host by blocking bacterial proliferation as well as endotoxin-mediated effects, not only as components of the intracellular antibacterial arsenal of the neutrophil, but also as potentially therapeutic extracellular agents.
Inhaled steroids in children: adrenal suppression and growth impairment
Authors: K-H. Carlsen, J. Gerritsen
Journal: European Respiratory Journal (2002)

Inhaled steroids have been used for many years. The first report of their beneficial use in asthmatic children was published almost 30 yrs ago 1. With increasing knowledge of the side-effects of systemically administered steroids, there has been a steady increase in the use of inhaled steroids, and they are presently considered to be the most important treatment for asthma. Inhaled steroids are the cornerstone of all guidelines on asthma treatment 2–4. They reduce symptoms in children with asthma 5, improve quality of life in asthmatic children and their families 6, decrease patients' and their parents' absence from school/work 7, reduce airway inflammation 8, and improve lung function 9, bronchial responsiveness 10 and exercise-induced asthma 11, 12. The sale and use of inhaled steroids has markedly increased in Nordic countries since the late 1980s, which has probably had an impact upon the admission rate of childhood asthma in these countries. In older children, the admission 13 and particularly readmission 14 rates for acute asthma have decreased in these countries. The use of inhaled steroids has thus had a major impact upon daily life and the “mastering” of asthma in asthmatic children.

Despite the beneficial effects of inhaled steroids in childhood asthma, general agreement as to how early to start treatment has not been reached. This is mostly due to the general fear of the side-effects of inhaled steroids, but also because of an awareness of the possible effects upon lung growth in young children, as has been reported by the use of systemic steroids in animal experiments 15.

The local side-effects of inhaled steroids on skin, the mucous membranes of the respiratory tract, and the oropharyngeal area are also well known, but have received much less attention than the …
Active Adaptation of the Tethered Mitral Valve
Authors: Jacob P. Dal-Bianco, Elena Aikawa, Joyce Bischoff, J. Luis Guerrero, Mark D. Handschumacher, Suzanne Sullivan, Benjamin Johnson, James S. Titus, Yoshiko Iwamoto, Jill Wylie-Sears, Robert A. Levine, Alain Carpentier
Journal: Circulation (2009)

Background— In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching. Methods and Results— Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61±6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4±1.3 cm 2 (17±10%) from 14.3±1.9 to 16.7±1.9 cm 2 ( P =0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18±0.14 versus 0.42±0.14 mm; P &lt;0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31 + ) coexpressing α-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41±19% versus 9±5%; P =0.02), indicating endothelial-mesenchymal transdifferentiation. α-Smooth muscle actin–positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial α-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells. Conclusions— Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation.
Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study
Authors: S A Mitchell
Journal: Gut (2002)

<b>Background and aims:</b> The strong clinical association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) suggests common factors in their pathogenesis. Smoking, previous appendectomy, and tonsillectomy have been associated with a decreased risk of developing UC. In this study, our aim was to examine these risk factors in patients with PSC with and without underlying inflammatory bowel disease (IBD). <b>Methods:</b> The smoking habits and history of previous appendectomy and/or tonsillectomy of 170 patients with PSC, 41 without underlying IBD, 170 patients with UC but normal liver function tests, and 170 age and sex matched community controls were obtained by questionnaire. <b>Results:</b> A total of 112 PSC patients (66%) had never smoked compared with 66 controls (39%). Only 12 PSC patients (7%) were current smokers versus 43 controls (25%). The resultant odds ratio of having PSC was 0.17 (95% confidence interval (CI) 0.08–0.35) among current smokers and 0.33 (95% CI 0.21–0.52) among ever (former+current) smokers. Among former smokers, the odds of having PSC were also significantly decreased (odds ratio 0.45, 95% CI 0.26–0.73; p&lt;0.05). In the subgroup of PSC patients without IBD, only 5% were current smokers versus 26% of matched controls, and never smokers were overrepresented (68% <i>v</i> 37%). The rate of previous appendectomy was similar in all three study groups (14%, 12%, and 13%) but the frequency of tonsillectomy was reduced in the PSC group (21% <i>v</i> 31%; p=0.05). <b>Conclusion:</b> PSC, like UC, is a disease of non-smokers as the odds of having PSC was significantly decreased among current and former smokers. The association between non-smoking and PSC was independent of whether the PSC patient had underlying IBD. Previous tonsillectomy but not appendectomy may also be associated with a decreased risk of PSC but this warrants further study.
Angiokeratoma circumscriptum of the penis
Authors: M. Saha, R. Barlow, C.B. Bunker
Journal: British Journal of Dermatology (2006)

Journal Article Angiokeratoma circumscriptum of the penis Get access M. Saha, M. Saha Department of Dermatology, Chelsea and Westminster Hospital, London SW10 9NH, U.K. St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. E‐mail: monikasaha@doctors.net.uk Search for other works by this author on: Oxford Academic Google Scholar R. Barlow, R. Barlow Department of Dermatology, Chelsea and Westminster Hospital, London SW10 9NH, U.K. St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. E‐mail: monikasaha@doctors.net.uk Search for other works by this author on: Oxford Academic Google Scholar C.B. Bunker C.B. Bunker Department of Dermatology, Chelsea and Westminster Hospital, London SW10 9NH, U.K. St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K. E‐mail: monikasaha@doctors.net.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 4, 1 April 2006, Pages 775–776, https://doi.org/10.1111/j.1365-2133.2005.07120.x Published: 01 April 2006
Delivery of definable number of drug or growth factor loaded poly(dl-lactic acid-co-glycolic acid) microparticles within human embryonic stem cell derived aggregates
Authors: Omar Qutachi, Kevin M. Shakesheff, Lee D.K. Buttery
Journal: Journal of Controlled Release (2013)

Embryoid bodies (EBs) generated from embryonic stem cells are used to study processes of differentiation within a three dimensional (3D) cell environment. In many instances however, EBs are dispersed to single cell suspensions with a subsequent monolayer culture. Moreover, where the 3D integrity of an EB is maintained, cytokines or drugs of interest to stimulate differentiation are often added directly to the culture medium at fixed concentrations and effects are usually limited to the outer layers of the EB. The aim of this study was to create an EB model with localised drug and or growth factor delivery directly within the EB. Using poly(DL-lactic acid-co-glycolic acid) microparticles (MPs) with an average diameter of 13μm, we have demonstrated controllable incorporation of defined numbers of MPs within human ES cell derived EBs, down to 1 MP per EB. This was achieved by coating MPs with human ES cell lysate and centrifugation of specific ratios of ES cells and MPs to form 3D aggregates. Using MPs loaded with simvastatin (pro or active drug) or BMP-2, we have demonstrated osteogenic differentiation within the 3D aggregates, maintained in culture for up to 21days, and quantified by real time QPCR for osteocalcin. Immunostaining for RUNX2 and osteocalcin, and also histochemical staining with picrosirius red to demonstrate collage type 1 and Alizarin red to demonstrate calcium/mineralisation further demonstrated osteogenic differentiation and revealed regional staining associated with the locations of MPs within the aggregates. We also demonstrated endothelial differentiation within human ES cell-derived aggregates using VEGF loaded MPs. In conclusion, we demonstrate an effective and reliable approach for engineering stem aggregates with definable number of MPs within the 3D cellular structure. We also achieved localised osteogenic and endothelial differentiation associated with MPs releasing encapsulated drug molecules or cytokines directly within the cell aggregate. This provides a powerful tool for controlling and investigating differentiation within 3D cell cultures and has applications to drug delivery, drug discovery, stem cell biology, tissue engineering and regenerative medicine.
Randomization for concealment
Authors: David R Cox
Journal: Journal of the Royal Society of Medicine (2010)

It is a matter of concern in many areas of investigation that systematic distortions can arise from the intervention of personal judgements. This issue was raised in the last paper (published posthumously) by WS Gosset (who wrote under the pseudonym ‘Student’), a chemist who rose to a senior position in Guiness’s brewery in Dublin and London. The focus of his paper was his disagreement with RA Fisher about the relative merits of creating experimental groups: Gosset favoured systematic arrangements, such as alternation; Fisher rejected these in favour of random allocation. Gosset did agree one potential advantage of random allocation, however, when he wrote:
Part 12: Cardiac Arrest in Special Situations
Authors: Terry L. Vanden Hoek, Laurie J. Morrison, Michael Shuster, Michael Donnino, Elizabeth Sinz, Eric J. Lavonas, Farida M. Jeejeebhoy, Andrea Gabrielli
Journal: Circulation (2010)

Part 12.1: Cardiac Arrest Associated With AsthmaAsthma is responsible for more than 2 million visits to the emergency department (ED) in the United States each year, with 1 in 4 patients requiring admission to a hospital. 1Annually there are 5,000 to 6,000 asthma-related deaths in the United States, many occurring in the prehospital setting. 2 Severe asthma accounts for approximately 2% to 20% of admissions to intensive care units, with up to one third of these patients requiring intubation and mechanical ventilation. 3This section focuses on the evaluation and treatment of patients with near-fatal asthma.Several consensus groups have developed excellent guidelines for the management of asthma that are available on the World Wide Web
Hodgkin lymphoma in 2 children with chronic granulomatous disease
Authors: Saul Oswaldo Lugo Reyes, Felipe Suarez, Rose-Marie Herbigneaux, Hélène Pacquement, Yves Réguerre, Jean-Pierre Rivière, Maylis de Suremain, Yoann Rose, Jacqueline Feinberg, Nizar Malahoui, Alain Fischer, Stéphane Blanche, Jean-Laurent Casanova, Capucine Picard, Jacinta Bustamante
Journal: Journal of Allergy and Clinical Immunology (2010)
Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation
Authors: J R McDermott
Journal: Gut (2005)

<b>Background and aims:</b> Gastrointestinal inflammation reduces food intake but the biological mechanisms explaining suppressed feeding during inflammation are unknown. We have used a model of upper gut infection (<i>Trichinella spiralis</i> in the mouse) to study the effect of inflammation on food intake, and explored the role of a key enteroendocrine cell (EEC) in the regulation of feeding by the immune response. <b>Methods:</b> Food intake of NIH mice infected with the intestinal nematode <i>Trichinella spiralis</i> was measured. Duodenal cholecystokinin (CCK) cells were counted. Plasma CCK was measured. Infected mice were treated with a specific CCK<sub>1</sub> receptor antagonist, and food intake reassessed. The influence of the immune response on food intake and CCK was mechanistically examined by treating mice with CD4 or mast cell neutralising antibodies. The role of the T helper 2 response was further explored in mice genetically deficient for interleukin (IL)-4, IL-13, or IL-4Rα (receptor α subunit). <b>Results:</b> Food intake of infected mice was significantly reduced at the temporal peak of intestinal inflammation. CCK expressing EEC were upregulated in infected mice, and plasma CCK levels were increased. A CCK<sub>1</sub> receptor antagonist restored the food intake of infected mice to a significant degree. Furthermore, suppression of food intake was completely abolished in the absence of CD4<sup>+</sup> T lymphocytes or IL-4Rα. <b>Conclusions:</b> The data show for the first time that intestinal inflammation results in reduced food intake due to upregulation of CCK. Moreover, following infection, food intake and CCK expressing cells are under the specific control of CD4<sup>+</sup> T-cells, via release of IL-4 and IL-13.
Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase
Authors: Shani Ben-Shlomo, Isabel Zvibel, Mati Shnell, Amir Shlomai, Elena Chepurko, Zamir Halpern, Nir Barzilai, Ran Oren, Sigal Fishman
Journal: Journal of Hepatology (2010)
Breast Cancer Risk in Rats Fed a Diet High in n-6 Polyunsaturated Fatty Acids During Pregnancy
Authors: L. Hilakivi-Clarke, I. Onojafe, M. Raygada, E. Cho, R. Clarke, M. E. Lippman
Journal: JNCI Journal of the National Cancer Institute (1996)

BackgroundWomen who took the synthetic estrogen di-ethylstilbestrol during pregnancy exhibit an elevated risk of breast cancer, whereas those who suffered from preeclampsia, which is associated with low circulating pregnancy estrogens, exhibit a reduced risk. Since a high-fat diet may increase circulating estrogen levels and possibly breast cancer risk, dietary factors during pregnancy could influence the risk of developing this disease.