tbuckley/cabot-search huggingface dataset:
Sonic Hedgehog–Modified Human CD34+ Cells Preserve Cardiac Function After Acute Myocardial Infarction
Authors: Alexander R. Mackie, Ekaterina Klyachko, Tina Thorne, Kathryn M. Schultz, Meredith Millay, Aiko Ito, Christine E. Kamide, Ting Liu, Rajesh Gupta, Susmita Sahoo, Sol Misener, Raj Kishore, Douglas W. Losordo
Journal: Circulation Research (2012)

Ischemic cardiovascular disease represents one of the largest epidemics currently facing the aging population. Current literature has illustrated the efficacy of autologous, stem cell therapies as novel strategies for treating these disorders. The CD34+ hematopoetic stem cell has shown significant promise in addressing myocardial ischemia by promoting angiogenesis that helps preserve the functionality of ischemic myocardium. Unfortunately, both viability and angiogenic quality of autologous CD34+ cells decline with advanced age and diminished cardiovascular health.To offset age- and health-related angiogenic declines in CD34+ cells, we explored whether the therapeutic efficacy of human CD34+ cells could be enhanced by augmenting their secretion of the known angiogenic factor, sonic hedgehog (Shh).When injected into the border zone of mice after acute myocardial infarction, Shh-modified CD34+ cells (CD34(Shh)) protected against ventricular dilation and cardiac functional declines associated with acute myocardial infarction. Treatment with CD34(Shh) also reduced infarct size and increased border zone capillary density compared with unmodified CD34 cells or cells transfected with the empty vector. CD34(Shh) primarily store and secrete Shh protein in exosomes and this storage process appears to be cell-type specific. In vitro analysis of exosomes derived from CD34(Shh) revealed that (1) exosomes transfer Shh protein to other cell types, and (2) exosomal transfer of functional Shh elicits induction of the canonical Shh signaling pathway in recipient cells.Exosome-mediated delivery of Shh to ischemic myocardium represents a major mechanism explaining the observed preservation of cardiac function in mice treated with CD34(Shh) cells.
Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease
Authors: R J Wakefield
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To determine the prevalence of subclinical synovitis using ultrasound (US) imaging of both painful and asymptomatic joints, in patients with early (&lt;12 months), untreated oligoarthritis (⩽5 joints). <b>Methods:</b> Eighty patients underwent a detailed clinical assessment by two physicians. All painful joints were identified, which were immediately scanned by a sonographer. In the last 40 patients, an additional standard group of joints was scanned to establish the prevalence of synovitis in asymptomatic joints. <b>Results:</b> In 80 patients, 644 painful joints (with and without clinical synovitis) were identified and each underwent a US assessment. Of these joints, 185 had clinical synovitis, of which, US detected synovitis in only 79% (147/185). In the other 38 joints US demonstrated tenosynovitis instead of synovitis in 12 joints and possible, but not definite, synovitis in 11 joints. Fifteen joints were, however, normal on US. In 459 joints that were not clinically synovitic, US detected synovitis in 33% (150/459). In 64% (51/80) of patients, US detected synovitis in more joints than clinical examination and in 36% (29/80) of patients, US detected a polyarthritis (&gt;6 joints). Of the 826 asymptomatic (non-painful) joints scanned, 13% (107/826) had US detected synovitis. <b>Conclusion:</b> Sonography detected more synovitis than clinical examination in patients with oligoarthritis. In almost two thirds of patients there was evidence of subclinical disease while one third could be reclassified as polyarticular. These findings suggest that a definition of oligoarthritis based purely on clinical findings may be inappropriate, which may have important implications for disease management.
Evaluating the Safety of Diabetes Drugs
Authors: Robert I. Misbin
Journal: Diabetes Care (2005)

Problems had been festering at the Food and Drug Administration (FDA) for years (1,2). In 2004, the abscess finally broke. First came the recognition that widely used antidepressants were associated with suicide in young patients, and then came the withdrawal of Vioxx. Drugs in diabetes and metabolism have not been spared. The obesity drug Meridia and the lipid-lowering agent Crestor are two of the five drugs whose safety was challenged by FDA epidemiologist Dr. David Graham in testimony before a Senate committee (3).

Unique among drug withdrawals is the diabetes drug phenformin, which was declared an imminent hazard by Secretary Califano and was removed from the market in 1977 because of lactic acidosis (4). As was the case with Vioxx, more recent withdrawals of diabetes and metabolism drugs were done by the manufacturers. The obesity drug Redux was removed in 1997 because of heart valvulopathy (5). The diabetes drug Rezulin was removed in 2000 because of liver failure and the lipid-lowering drug Baycol in 2001 because of rhabdomyolysis (6).

But the news for diabetes drugs has not been all bad. The concern about lactic acidosis that accompanied the approval of Glucophage has been found to be greatly exaggerated (7). Despite reports of liver injury that appeared shortly after the approval of Avandia, there is little, if any, evidence that either Avandia or the related drug Actos increase the risk of liver injury over background (8).

One lesson that should be learned from these examples is that it is hazardous to make firm conclusions about the safety of a new drug. The approval of a new drug is based on safety data from a few thousand patients treated under the intense medical supervision of a clinical trial. The very patients who are likely to have side …
Erdheim-Chester disease
Authors: B. Rhodes
Journal: Journal of the Royal Society of Medicine (2005)

Erdheim-Chester diseaseDr Lee and his colleagues (April 2005 JRSM 1 ) describe a case of renal failure in which the radiographic appearance of bone pointed to Erdheim-Chester disease, a histiocytosis.Among the organs affected in this condition they mention pericardium.We think it important to emphasize the frequency with which heart, pericardium and great vessels are affected.Recording 6 new patients with cardiovascular involvement, Haroche et al. 2 have reviewed all 178 reported cases of Erdheim-Chester disease.56% had periaortic fibrosis, 44% pericardial infiltration and/or effusions and 31% myocardial infiltration.Interestingly, 6 patients had a right atrial myxoma.Of the 58 patients with follow-up data, 31% died from cardiovascular complications.
Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study
Authors: T. André, H. Blons, M. Mabro, B. Chibaudel, J-B. Bachet, C. Tournigand, M. Bennamoun, P. Artru, S. Nguyen, C. Ebenezer, N. Aissat, A. Cayre, F. Penault-Llorca, P. Laurent-Puig, A. de Gramont
Journal: Annals of Oncology (2012)
Hypoxic Preconditioning Enhances the Benefit of Cardiac Progenitor Cell Therapy for Treatment of Myocardial Infarction by Inducing CXCR4 Expression
Authors: Yao Liang Tang, Wuqiang Zhu, Min Cheng, Lijuan Chen, John Zhang, Tao Sun, Raj Kishore, M. Ian Phillips, Douglas W. Losordo, Gangjian Qin
Journal: Circulation Research (2009)

Myocardial infarction rapidly depletes the endogenous cardiac progenitor cell pool, and the inefficient recruitment of exogenously administered progenitor cells limits the effectiveness of cardiac cell therapy. Recent reports indicate that interactions between the CXC chemokine stromal cell–derived factor 1 and its receptor CXC chemokine receptor 4 (CXCR4) critically mediate the ischemia-induced recruitment of bone marrow–derived circulating stem/progenitor cells, but the expression of CXCR4 in cardiac progenitor cells is very low. Here, we studied the influence of hypoxia on CXCR4 expression in cardiac progenitor cells, on the recruitment of intravenously administered cells to ischemic heart tissue, and on the preservation of heart function in a murine myocardial infarction model. We found that hypoxic preconditioning increased CXCR4 expression in CLK (cardiosphere-derived, Lin − c-kit + progenitor) cells and markedly augmented CLK cell migration (in vitro) and recruitment (in vivo) to the ischemic myocardium. Four weeks after surgically induced myocardial infarction, infarct size and heart function were significantly better in mice administered hypoxia-preconditioned CLK cells than in mice treated with cells cultured under normoxic conditions. Furthermore, these effects were largely abolished by the addition of a CXCR4 inhibitor, indicating that the benefits of hypoxic preconditioning are mediated by the stromal cell–derived factor 1/CXCR4 axis, and that therapies targeting this axis may enhance cardiac-progenitor cell–based regenerative therapy.
Direct Evidence for Endothelial Vascular Endothelial Growth Factor Receptor-1 Function in Nitric Oxide–Mediated Angiogenesis
Authors: Shakil Ahmad, Peter W. Hewett, Ping Wang, Bahjat Al-Ani, Melissa Cudmore, Takeshi Fujisawa, Jody J. Haigh, Ferdinand le Noble, Ling Wang, Debabrata Mukhopadhyay, Asif Ahmed
Journal: Circulation Research (2006)

Vascular endothelial growth factor-A (VEGF) is critical for angiogenesis but fails to induce neovascularization in ischemic tissue lesions in mice lacking endothelial nitric oxide synthase (eNOS). VEGF receptor-2 (VEGFR-2) is critical for angiogenesis, although little is known about the precise role of endothelial VEGFR-1 and its downstream effectors in this process. Here we have used a chimeric receptor approach in which the extracellular domain of the epidermal growth factor receptor was substituted for that of VEGFR-1 (EGLT) or VEGFR-2 (EGDR) and transduced into primary cultures of human umbilical vein endothelial cells (HUVECs) using a retroviral system. Activation of HUVECs expressing EGLT or EGDR induced rapid phosphorylation of eNOS at Ser1177, release of NO, and formation of capillary networks, similar to VEGF. Activation of eNOS by VEGFR-1 was dependent on Tyr794 and was mediated via phosphatidylinositol 3-kinase, whereas VEGFR-2 Tyr951 was involved in eNOS activation via phospholipase Cgamma1. Consistent with these findings, the VEGFR-1-specific ligand placenta growth factor-1 activated phosphatidylinositol 3-kinase and VEGF-E, which is selective for VEGFR-2-activated phospholipase Cgamma1. Both VEGFR-1 and VEGFR-2 signal pathways converged on Akt, as dominant-negative Akt inhibited the NO release and in vitro tube formation induced following activation of EGLT and EGDR. The identification Tyr794 of VEGFR-1 as a key residue in this process provides direct evidence of endothelial VEGFR-1 in NO-driven in vitro angiogenesis. These studies provide new sites of modulation in VEGF-mediated vascular morphogenesis and highlight new therapeutic targets for management of vascular diseases.
Galectin-3 Cleavage: A Novel Surrogate Marker for Matrix Metalloproteinase Activity in Growing Breast Cancers
Authors: Pratima Nangia-Makker, Tirza Raz, Larry Tait, Victor Hogan, Rafael Fridman, Avraham Raz
Journal: Cancer Research (2007)

Abstract Failed therapies directed against matrix metalloproteinases (MMP) in cancer patients may be attributed, in part, to lack of diagnostic tools to differentiate between pro-MMPs and active MMPs, which indicate whether a treatment is efficacious or not. Because galectin-3 is cleavable in vitro by MMPs, we have developed differential antibodies recognizing its cleaved and noncleaved forms and tested their clinical utilization as a surrogate diagnostic marker for the presence of active MMPs in growing breast cancers. Wild-type and cleavage-resistant galectin-3 were constructed and expressed in galectin-3–null human breast carcinoma cells (BT-549). Tumorigenic and angiogenic potential of the clones was studied by injections into nude mice. MMP-2, MMP-9, full-length, and cleaved galectin-3 were localized in the xenografts by immunohistochemical analysis of paraffin-embedded sections using specific antibodies. Activities of MMP-2/9 were corroborated by in situ zymography on frozen tissue sections. Galectin-3 cleavage was shown in vivo by differential antibody staining and colocalized with predicted active MMPs both in mouse xenografts and human breast cancer specimens. In situ zymography validated these results. In addition, BT-549 cells harboring noncleavable galectin-3 showed reduced tumor growth and angiogenesis compared with the wild-type. We conclude that galectin-3 cleavage is an active process during tumor progression and could be used as a simple, rapid, and reliable surrogate marker for the activities of MMPs in growing breast cancers. [Cancer Res 2007;67(24):11760–8]
Food and Beverage Marketing in Schools
Authors: Jennifer L. Harris, Tracy Fox
Journal: JAMA Pediatrics (2014)

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 Pediatrics 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 Pediatrics journal
Epithelial Cancer of the Ovary
Authors: C M. Steel
Journal: BMJ (1996)

Frank G Lawton, Jan P Neijt, Kenneth D Swenerton BMJ Publishing Group, pounds sterling44.95, pp 299 ISBN 0 7279 0851 0

What's new in ovarian cancer? Not, alas, the expected outcome. Nevertheless only the most hardened cynic would dismiss the progress made in recent years in drug development, or in technologies for screening and accurate assessment of response to treatment. Nor should we discount the promise held out by new discoveries on the cellular and molecular basis of the disease. Given the availability of several up to date publications, …
Association of the TNF-α-C-857T Polymorphism With Resistance to the Cholesterol-Lowering Effect of HMG-CoA Reductase Inhibitors in Type 2 Diabetic Subjects
Authors: Toru Takahashi, Kazuma Takahashi, Mitsuhiro Yamashina, Chihaya Maesawa, Takashi Kajiwara, Haruhito Taneichi, Noriko Takebe, Yoshihito Kaneko, Tomoyuki Masuda, Jo Satoh
Journal: Diabetes Care (2009)

OBJECTIVE An association of the C-857T polymorphism of the tumor necrosis factor-α (TNF-α) gene promoter region with LDL cholesterol levels has been reported. This study was designed to evaluate the relationship between the TNF-α-C-857T polymorphism and LDL cholesterol levels according to statin treatment in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS DNA was obtained from 322 Japanese subjects (160 male and 162 female) with type 2 diabetes, and TNF-α-C-857T polymorphisms were determined by direct sequencing. Serum LDL cholesterol was measured by a direct method. RESULTS Although serum LDL cholesterol levels were significantly higher in the T carriers (C/T + T/T) than in the non–T carriers (C/C) (3.14 ± 0.86 vs. 2.89 ± 0.75 mmol/l, P &amp;lt; 0.05), there was no difference in LDL cholesterol levels between the non–T carriers and the T carriers in statin-untreated subjects (2.87 ± 0.73 vs. 2.89 ± 0.76 mmol/l, NS), whereas in statin-treated subjects, LDL cholesterol levels were significantly higher in the T carriers than in the non–T carriers (3.43 ± 0.89 vs. 2.90 ± 0.78 mmol/l, P = 0.0007). There were no differences in HDL cholesterol and triglyceride levels between the non–T carriers and the T carriers in both statin-treated and -untreated subjects. The percent decrease in LDL cholesterol levels after administration of statins was significantly smaller in the T carriers compared with the non–T carriers (27.6 vs. 36.4%, P = 0.031). CONCLUSIONS The mutant allele of the C-857T promoter polymorphism of the TNF-α gene may predispose to resistance to the LDL cholesterol–lowering effect of statins and could be one of the markers used to predict the efficacy of statins.
Differential effects of the early and late intrauterine environment on corticotrophic cell development
Authors: Timothy G. Butler, Jeff Schwartz, I. Caroline McMillen
Journal: Journal of Clinical Investigation (2002)

The developing embryo and fetus respond to a range of intrauterine stressors, but the effect of chronic intrauterine stress on the programmed development of pituitary corticotrophs has not been investigated. We have used a pregnant sheep model in which the embryonic environment at conception has been surgically perturbed by uterine carunclectomy. This procedure results in the development of fetuses that either are placentally restricted and chronically hypoxemic or that demonstrate compensatory placental growth and maintain normoxemia throughout late gestation. We found that uterine carunclectomy resulted in the emergence of a population of non–corticotrophin-releasing hormone (non-CRH) target cells that secreted high amounts of adrenocorticotrophic hormone (ACTH) in the fetal pituitary. This change in corticotroph development was independent of late-gestation hypoxemia. However, chronic hypoxemia during late gestation (in either carunclectomized or non-carunclectomized uterine environments) resulted in a reduction in the proportion of ACTH stored in CRH-target. Thus, the early and late intrauterine environments differentially program the development of specific corticotrophic cell types in the fetal pituitary. These patterns of altered corticotroph development are important given the central roles of the hypothalamo-pituitary-adrenal axis in the fetal adaptive response to intrauterine stress and in the early programming of adult disease.
Hapten-specific T cell lines mediating delayed hypersensitivity to contact-sensitizing agents.
Authors: W R Thomas, P L Mottram, J F Miller
Journal: The Journal of Experimental Medicine (1982)

Continuous cultures of T cells from the lymph nodes of mice sensitized to the contact sensitizers 4-ethoxymethylene-2-phenyl oxazolone or picryl chloride have been established. For continuous proliferation, the lines required specific antigen, syngeneic antigen-presenting cells, and growth factors from the supernatant of concanavalin-A-stimulated lymphoid cultures. Cells from the lines showed antigen specificity and major histocompatibility complex restriction in proliferation assays and in delayed hypersensitivity. They could mediate delayed hypersensitivity to the sensitizer presented as a reactive hapten or coupled to keyhold limpet hemocyanin.
Cytoplasmic transfer in assisted reproduction
Authors: Jason A. Barritt, Steen Willadsen, Carol Brenner, Jacques Cohen
Journal: Human Reproduction Update (2001)

This report details the use of cytoplasmic transfer in human oocytes. The introduction of a small amount of ooplasm from a donor oocyte or zygote may alter the function of oocytes, with probable deficiencies. Cytoplasmic transfer from fertile donor oocytes or zygotes into compromised oocytes from patients with recurrent implantation failure after assisted reproduction has now led to the birth of nearly 30 healthy babies worldwide. Transfer of small amounts of cytoplasm probably involves mRNAs, proteins and mitochondria, as well as other factors and organelles. Even though the use of cytoplasmic transfer has been employed in several IVF clinics--and pregnancies have resulted--it is not known definitively whether the physiology of the early embryo is affected. This review outlines the experimental cytoplasmic transfer techniques and postulates the future impact in assisted reproduction.
Ultrasound-assisted transthoracic biopsy: fine-needle aspiration or cutting-needle biopsy?
Authors: A. H. Diacon, J. Theron, P. Schubert, K. Brundyn, M. Louw, C. A. Wright, C. T. Bolliger
Journal: European Respiratory Journal (2006)

The present study compared the diagnostic yield of ultrasound-assisted cutting-needle biopsy (CNB) and fine-needle aspiration biopsy (FNAB) in chest lesions. A physician performed ultrasound and FNAB with a 22-G spinal needle in all patients, directly followed by a 14-G CNB in patients without contraindication. A total of 155 consecutive lesions arising from the lung (74%), pleura (12%), mediastinum (11%) or chest wall (3%) in patients with a final diagnosis of lung carcinoma (74%), other malignant tumours (12%), non-neoplastic disease (9%) or unknown (5%) were prospectively included. The overall diagnostic yield was 87%. Combined specimens were obtained in 123 lesions (79%). In these, yields of FNAB, CNB and both methods combined were 82, 76 and 89%, respectively. FNAB was significantly better than CNB in lung carcinoma (95 versus 81%) but CNB was superior in noncarcinomatous tumours and in benign lesions. On-site cytology was 90% sensitive and 100% specific for predicting a positive FNAB. One patient required drainage for pneumothorax (0.6%). Ultrasound-assisted fine-needle aspiration biopsy performed by chest physicians is an accurate and safe initial diagnostic procedure in patients with a high clinical probability of lung carcinoma. All other patients should undergo concurrent fine-needle aspiration biopsy and cutting-needle biopsy.
Contrasuppression. A novel immunoregulatory activity.
Authors: R K Gershon, D D Eardley, S Durum, D R Green, F W Shen, K Yamauchi, H Cantor, D B Murphy
Journal: The Journal of Experimental Medicine (1981)

We have described an interaction between two T cells subsets that results in interference with the expression of Ly-1-, 2+ (Ly-2) T cell-mediated suppression. We refer to this novel immunoregulatory activity as contrasuppression. The T cell responsible for the induction of contrasuppression (inducer cell) expresses the phenotype Ly-1-, 2+;I-J+;Qa-1+. This phenotype distinguishes it from the suppressor effector cells which we find to be I-J-2.3. An I-J+ soluble mediator from the contrasuppressor inducer cell acts on another cell (acceptor cell) that expresses the phenotype Ly-1+, 2+; I-J+; Qa-1+. This phenotype distinguishes it from T helper cells. Both the inducer cell (or its biologically active mediator) and its acceptor cell are required for the expression of contrasuppression. Because contrasuppressor cells can block the suppressive activity of cell-free mediators released by Ly-2 suppressor T cells, the mechanism of contrasuppression is either separated from or in addition to the inactivation of suppressor cells themselves. The potential importance of contrasuppressor activity in the regulation of suppressor T cell activity in allowing immunologic memory to be expressed and in permitting microenvironmental immune regulation is discussed.