tbuckley/cabot-search huggingface dataset:
56. Intraplacental Gene Transfer of IGF-1 Corrects Intrauterine Growth Restriction in the Rabbit Model
Authors: Joseph T. Bruder, Ping Chen, Kurt Kroeger, Melissa Hamilton, Miguel Carrion, Douglas E. Brough, Lisa L. Wei, C. Richter King, Peter A. Campochiaro, Peter Gehlbach
Journal: Molecular Therapy (2004)

The growth of abnormal blood vessels in the eye, associated with proliferative diabetic retinopathy, retinopathy of prematurity and wet age-related macular degeneration (AMD), is the major cause of blindness in developed countries. Current treatments that destroy or inhibit the growth of existing blood vessels can delay vision loss but do not affect the underlying disease and neovascularization is a recurring problem. Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic and neuroprotective protein that is naturally produced in the eye. When delivered to the eye via an adenovirus vector, PEDF can block growth of new blood vessels and trigger the regression of established abnormal vessels in animal models for AMD and diabetic retinopathy.
The role of IgG antibodies in allergy and immunotherapy
Authors: R. Aalberse
Journal: Allergy (2011)

In specific immunotherapy (SIT), a beneficial response is associated with an increase in allergen-specific IgG(4) . This does not indicate that IgE-producing B cells have switched to IgG(4) production, because in human DNA, IgE is downstream from IgG(4) . Thus, by conventional switching, B cells should produce IgG(4) before IgE. This presentation discusses three possible hypotheses explaining the favourable association between IgG(4) and SIT, including that SIT causes B cells to become regulatory. Regulatory B cells may produce cytokines like IL-10 that promote IgG(4) production. IgG(4) can undergo in vitro switching to create bispecific antibodies that recognize more than one antigen, which has important consequences for reducing IgE-allergen complexes in immunotherapy.
US manufacturers resist moves to sell drugs over the counter
Authors: Fred Charatan
Journal: BMJ (2001)

An advisory panel of the US Food and Drug Administration (FDA) has voted overwhelmingly that three allergy remedies—loratadine, cetirizine, and fexofenadine—are safe enough to be bought at pharmacies and supermarkets without a doctor's prescription. But the manufacturers of the drugs are resisting the idea.

Loratadine and cetirizine are already available over the counter in the United Kingdom (as Clarityn and Zirtek respectively), provided that the packs do not contain more than 10 days' supply of the drug. Fexofenadine, marketed in the United Kingdom as Telfast and in the United …
Synovial Fluid Changes in Joint Disease.
Authors: Marian W. Ropes, Walter Bauer
Journal: Annals of Internal Medicine (1953)

This little monograph presents the authors' 20 years of experience with articular anatomy, physiology, and pathology. The book begins with a discussion of normal articular fluid. Much of the work presented was done on cattle, but the findings are apparently comparable to those in fluid recovered post mortem from human joints. The second chapter presents a general analysis of the variations that can occur in pathological states. The comprehensiveness of this section is reflected in its subheadings: pressure, amount and gross appearance of fluid, bacteriology, cytology, proteins, electrolytes, nonelectrolytes (including sugar, lactate, lipids, and cholesterol), enzymes, and mucin. On the basis of these studies, the authors divide abnormal joint fluids into two main groups: those characteristic of diseases of traumatic origin and those found in rheumatoid arthritis and diseases of infectious origin. In chapters 3 and 5 these two groups are discussed in detail and in relation to specific disease
Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor
Authors: Y Gazitt, E Tian, B Barlogie, CL Reading, DH Vesole, S Jagannath, J Schnell, R Hoffman, G Tricot
Journal: Blood (1996)
Abstract 4205: Mass-spectroscopy phosphorylation profiling identified differential activation of signaling molecules via spleen tyrosine kinase in B-cell receptor signaling and stromal cell stimulation in DLBCL and CLL cells that are inhibited by GS-9973
Authors: Julie A. Di Paolo, Astrid Clarke, Hong Rong, Emma Rousseau
Journal: Cancer Research (2014)

Abstract Dysregulation of protein kinase activity leading to aberrant or excessive downstream signaling is widely believed to underlay the pathogenesis of multiple cancers. The purpose of this study was to identify the spleen tyrosine kinase (SYK)-dependent phosphoproteins that were activated in a diffuse large B-cell lymphoma (DLBCL) cell line, DHL4, and primary chronic lymphocytic leukemia (CLL) cells, upon either B-cell receptor (BCR) activation, stromal cell contact, or in a resting state and demonstrate inhibition with a selective SYK inhibitor, GS-9973. A commercial PTMScan Direct procedure from Cell Signaling Technology was utilized in this assessment. Cell lysates generated from resting, αIgG treatment or HS-5 human stromal cell line contact were digested with trypsin and the resultant peptides were enriched by immunoprecipitation with either an anti-phosphotyrosine or anti-phosphoserine/threonine antibody cocktail, and subjected to mass spectrometric analysis to identify and quantify phosphorylated peptides. The phosphorylated peptide profile was then compared to a similarly treated lysate after incubation with 1 μM GS-9973. Protein phosphorylations that were significantly changed by &amp;lt; or &amp;gt; 2.5-fold with GS-9973 treatment were identified and confirmed, where possible, by western blot of DHL-4 lysates or in primary CLL samples with antibodies specific for the identified sites. PTMScan Direct analysis showed overlapping, but not equivalent, patterns of phosphorylated peptides upon αIgG or stromal cell activation. A shared set of GS-9973 inhibited phosphoproteins were identified including pSyk, pAkt, pMek, pErk, pJnk2, pPKCδ, and pS6 kinase. Western blot analysis validated 13 out of 14 proteins as being modulated by 1 μM GS-9973 treatment. Furthermore, dose-response inhibition was demonstrated for pAkt-T473, pBCR-Y177, pBlnk-Y84, pMek-S217/221, and pErk-T202/Y204 with EC50s ranging from 23 to 50 nM. These data support the concept that Syk inhibition can block multiple signaling pathways known to be important in malignant B-cells function. Furthermore, identification of these sites elucidates possible pharmacodynamic signatures of GS-9973 inhibition that may be followed in clinical investigations of GS-9973 in oncology. Citation Format: Julie A. Di Paolo, Astrid Clarke, Hong Rong, Emma Rousseau. Mass-spectroscopy phosphorylation profiling identified differential activation of signaling molecules via spleen tyrosine kinase in B-cell receptor signaling and stromal cell stimulation in DLBCL and CLL cells that are inhibited by GS-9973. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4205. doi:10.1158/1538-7445.AM2014-4205
Active Site Inhibited Factor VIIa (DEGR VIIa) Attenuates the Coagulant and Interleukin-6 and -8, but not Tumor Necrosis Factor, Responses of the Baboon to LD100Escherichia coli
Authors: F.B. Taylor, A.C.K. Chang, G. Peer, A. Li, M. Ezban, U. Hedner
Journal: Blood (1998)
Gene Therapy-Leukemia Link
Authors: Joan Stephenson
Journal: JAMA (2003)

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
Transmission of alpha-synuclein in Parkinson’s disease
Authors: Virginia M-Y Lee
Journal: Molecular Neurodegeneration (2013)

The accumulation of misfolded proteins is a fundamental pathogenic process in neurodegenerative diseases. However, the factors that trigger aggregation and spreading of α-synuclein (α-syn), the principal component of the intraneuronal inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs) that characterize Parkinson’s disease (PD) and dementia with LBs (DLB) in brain are poorly understood. We demonstrate that pre-formed fibrils (pffs) generated from recombinant α-syn enter cultured primary neurons generated from non-transgenic wildtype mice, promote recruitment of soluble endogenous α-syn into insoluble PD-like LBs and LNs. Accumulation of pathologic α-syn led to selective decreases in synaptic proteins, progressive impairments in neuronal excitability and connectivity, and eventually, neuron death. Moreover, we further show that in young asymptomatic α-syn transgenic (Tg) mice, intracerebral injections of synthetic α-syn pffs accelerate both the formation of intracellular LB/LN-like inclusions and the onset of neurological symptoms in recipient animals. Pathologic α-syn propagated along major central nervous system (CNS) pathways to regions far beyond injection sites and dramatically reduced survival with a highly reproducible interval from injection to death in inoculated animals. Thus, synthetic α-Syn pffs are wholly sufficient to initiate PD-like LBs/LNs and to transmit disease in primary neurons in vitro and Tg mice in vivo. Thus, these data support a prion-like cascade in synucleinopathies whereby cell-to-cell transmission and propagation of misfolded α-syn underlie the CNS proliferation of LBs/LNs. These findings open up new avenues for understanding the progression of PD and for developing novel therapeutics.
Abstract 20013: Adiponectin Protects Against Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice
Authors: Sumko Yoshida, José J Fuster, Kenneth Walsh
Journal: Circulation (2014)

Introduction & Objective:  Human population-based studies have found an independent association of obesity or visceral adiposity with abdominal aortic aneurysms (AAA) presence or increasing abdominal aortic diameter. However, the molecular mechanisms that link obesity to AAA development remain largely unknown. The unbalanced production of adipokines by dysfunctional adipose tissue in obese individuals greatly contributes to the increased cardiovascular risk associated with obesity. In this study we assessed the role of adiponectin, an anti-inflammatory adipokine typically down-regulated in obese individuals, in a model of AAA using apolipoprotein E/adiponectin double-knockout (ApoE-/- Apn-/-) mice.   Methods & Results:  We used an experimental model where angiotensin II (Ang II) is infused to hyperlipidemic ApoE-deficient mice for 28 days via a subcutaneous osmotic mini-pump to induce the formation of supra-renal AAA. We found that Ang II infusion for 7 days leads to a significant decrease in the expression of adiponectin in white adipose tissue in this model. Ang II infusion in male ApoE-/- Apn-/- mice led to a higher incidence of AAA and an increase in the maximal supra-renal aortic diameter compared with that of ApoE-/- mice as determined by ultrasound imaging (incidence of AAA: 100% vs. 42%, maximal aortic diameter: 2.12 ± 0.07 mm vs. 1.67 ± 0.09 mm, respectively at 28 days). Adiponectin deficiency augmented the early accumulation of macrophages into the aortic wall in Ang II-infused mice. Gene expression of the pro-inflammatory factors (TNFa, IL-1b, IL-6 and CCL2/MCP-1) was significantly increased in the supra-renal aorta of ApoE-/- Apn-/- relative to ApoE-/- mice after Ang II infusion. MMP-2 and MMP-9 activation was also augmented in the aorta of ApoE-/- Apn-/- mice compared to ApoE-/- mice.   Conclusions:  These results suggest that adiponectin exerts anti-inflammatory actions in the aortic wall that may protect against Ang II-induced AAA formation and growth in hyperlipidemic ApoE-deficient mice. Since adiponectin expression is significantly decreased in obese individuals, these results provide a potential mechanistic connection between obesity and AAA development.
The hospital of the future: Planning hospitals with limited evidence: a research and policy problem
Authors: N. Edwards, A. Harrison
Journal: BMJ (1999)

This is the last in a series of seven articles Research into the running and planning of hospital services has been neglected. This is surprising given the importance of hospitals for the public, politicians, and the healthcare system (box 1). ### Box 1: The importance of hospitals RETURN TO TEXT The articles in this series have shown that despite this importance there is a paucity of research and policy about how hospitals work, how they should be staffed, what size they should be, and how change can be managed. This article examines the main gaps in our knowledge about the future of the hospital sector identified in this series and examines the implications of this for policy and research (box 2). #### Summary points Hospital planning is done on the basis of limited research There is little evaluation of completed plans Many of the assumptions used are not stated clearly and are often based on limited or poor evidence—this applies to many of the arguments for increased centralisation The paradox of increasing admissions and falling bed numbers has contributed to the problems of responding to emergency care Planning needs to take into account the limited state of knowledge ### Box 2: Gaps in research There are many uncertainties … RETURN TO TEXT
Researchers find conflicting evidence on benefits of garlic
Authors: David Spurgeon
Journal: BMJ (2000)

People who consume raw or cooked garlic regularly face about half the risk of stomach cancer and two thirds the risk of colorectal cancer as people who eat little or none, reports a study in the October issue of the American Journal of Clinical Nutrition . But a second study published last week finds that the evidence about garlic is “inconclusive.”

The first study, which …
Roses and Tulips and Jasmine in a Glass With a Dragonfly and a Butterfly
Authors: M. Therese Southgate
Journal: JAMA (2000)

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
Tumorigenesis in Transplanted Irradiated and Nonirradiated Ovaries&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: W. U. Gardner
Journal: JNCI Journal of the National Cancer Institute (1961)

Over 300 hybrid mice (A × C57) were used to determine the incidences of ovarian tumors after irradiation and transplantation of ovaries. Female mice were given 87 or 175 r total-body radiation. Ovaries of these and non-irradiated donors were permitted to remain in place or transplanted sub-cutaneously or intratesticularly in male hosts. Some irradiated female mice received subcutaneous transplants of nonirradiated ovaries or of testes. Most of the intact and unilaterally castrated males had ovarian granulosa-cell tumors 600 to 700 days after a nonirradiated ovary was placed in the testis. Only about a third of the irradiated ovaries similarly grafted became tumorous. Nonirradiated ovaries grafted subcutaneously became tumorous in all the castrated male hosts, and two thirds of the irradiated ovaries became tumorous when transplanted in castrated male hosts. Approximately two thirds of the intact irradiated females and one third of the unilaterally ovariectomized, irradiated mice had ovarian tumors at death. Only 8 percent of the irradiated females that had an ovary transplanted subcutaneously from a young donor had ovarian tumors at death. Grafts of testis did not inhibit ovarian tumorigenesis. The environment provided by the male favored either ovarian tumorigenesis in grafted ovaries from both nonirradiated and irradiated donors or the growth of cells that had become tumorous. The incidence of lymphomas was higher in the male mice bearing grafts of irradiated ovaries. Two male mice bearing granulosa-cell tumors of the follicular type had mammary adenocarcinomas at death.
Abstract 20344: CCN5 Reverses Fibrosis and Cardiac Dysfunction Induced by Pressure Overload in Murine Models
Authors: Dongtak Jeong, Min-Ah Lee, Changwon Kho, Ahyoung Lee, Jae Gyun Oh, Jason Kovacic, Woo Jin Park, Roger Hajjar
Journal: Circulation (2014)

Introduction:  Cardiac fibrosis (CF) is associated with increased stiffness and diastolic dysfunction in failing hearts, and its severity is an independent predictor for clinical outcomes of heart failure patients. We previously showed that a matricellular protein CCN5 is anti-fibrotic and anti-hypertrophic in the mouse heart. However, the mechanisms involved in the anti-fibrotic activity of CCN5 remains unknown.   Methods:  In this study, we tested two different animal models. First, we generated pressure-overload heart failure models in mouse by TAC operation. Two months following gene transfer of CCN5, cardiac function was evaluated by echocardiography and invasive hemodynamics. Second, endothelial cells were recently shown to significantly contribute to CF through Endothelial-Mesenchymal Transition (EndoMT). Thus, we tested whether CCN5 inhibits EndoMT using the Scl-Cre-ERT; R26RstopYFP double Tg mouse, which is a widely used lineage traceable animal model. Protein and RNA expression levels of CCN5, several types of collagen and onventional TGF-beta signaling related genes were measured by western blot and RT-PCR analysis. Cell growth assay and apoptosis assay were also performed to evaluate the function of CCN5 in isolated rat adult cardiomyocytes and non-cardiomyocyte cells. Third, EndoMT and transdifferentiation assays were performed using human coronary endothelial cells (HCEC) and myofibroflast  in vitro .   Results:  First, CCN5 induces accelerated degradation of preformed fibrogenic materials like collagen in the heart. CCN5 reduces the fraction of Vimentin-positive fibroblasts that have already expanded in response to TAC. Second, our data showed that CCN5 can inhibit EndoMT both in vivo and in vitro. Finally, we found that CCN5 selectively induced apoptosis in myofibroblasts but not in cardiomyocytes or fibroblasts.   Conclusions:  CCN5 evoked reversal of preformed CF, which was accompanied by functional recovery of the failing hearts through the inhibition of transdifferentiation into myofibroblast and selective induction of apoptosis on myofibroblasts. Taken together, our results that CCN5 can effectively target fibrosis in the setting of heart failure.
Abstract 588: Lrig1 suppresses breast cancer stem cell expansion and promotes mesenchymal to epithelial transition
Authors: Nucharee Yokdang, Colleen Sweeney
Journal: Cancer Research (2014)

Abstract Leucine-rich repeats and immunoglobulin-like domains-1 (Lrig1) is known as a negative regulator of oncogenic receptor tyrosine kinases (ErbB, Met and Ret); and low Lrig1 expression correlates with poor patient prognosis in breast cancer. Lrig1 has been found to maintain stem cell quiescence and marks a subset of quiescent intestinal stem cells where its loss leads to heightened ErbB expression and duodenal adenomas. Lrig1 is defined as a tumor suppressor in healthy tissue such as intestine and epidermis where Lrig1 loss leads to stem cell expansion and epidermal hyperplasia. However, the role of Lrig1 in cancer stem cells (CSCs) and as a metastatic suppressor is unknown. Lrig1 expression is lowest in the highly invasive breast cancer subtype MDA-MB-231, and Lrig1 expression is highest in the weakly invasive luminal A breast cancer subtype. In patients, high Lrig1 expression exhibits longer relapse-metastatic free survival suggesting that Lrig1 expression protects against metastatic relapse. We hypothesized that Lrig1 suppresses breast CSC expansion and promotes mesenchymal to epithelial transition. Our results indicated that restoration of Lrig1 in highly aggressive cell lines promoted mesenchymal to epithelial transition (MET) and a loss of invasive morphology in 3D matrigel cell culture. These results demonstrated that Lrig1 suppressed cell proliferation in both 2D and 3D matrigel cultures and suppressed tumorsphere formation 10-fold. Importantly, we have shown that Lrig1 is down-regulated in the hTERT-immortalized mammary epithelial cell line-twist ER, (HMLE-twist ER) which undergoes EMT. When Lrig1 is knocked-down in HMLE-twist ER by shRNA, the results showed that loss of Lrig1 enhanced mesenchymal and stem cell expansion. These observations suggest that Lrig1 may play a role in EMT transition in metastasis, as well as providing a whole new area of therapeutic targets in breast cancer along with an improved basic understanding in cancer stem cell biology. Note: This abstract was not presented at the meeting. Citation Format: Nucharee Yokdang, Colleen Sweeney. Lrig1 suppresses breast cancer stem cell expansion and promotes mesenchymal to epithelial transition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 588. doi:10.1158/1538-7445.AM2014-588
The response of psoriasis to betamethasone valerate and clobetasol propionate.
Authors: M.F. CORBETT
Journal: British Journal of Dermatology (1976)

Twelve patients with symmetrical psoriasis were studied for a period of 6 months. Clobetasol propionate 0.05% ointment was applied to the lesions on one side and betamethasone valerate 0.1% ointment to those on the other side as a double‐blind controlled trial of these two treatments. All the patients showed a relative improvement on the side treated with clobetasol propionate. Clobetasol propionate‐treated lesions tended to clear for longer than the corresponding betamethasone valerate treated lesions. The condition of five of the patients was better at the end of the study period than at the beginning.