tbuckley/cabot-search huggingface dataset:
606. The NOD-SCID β2M Null Mouse Xenograft Model for Studying Activation, Expansion and GvHD Potential of Gene Transduced Human T Cells In Vivo
Authors: Jon E. Walker, Gerhard Bauer, Phillip Herrbrich, David Hess, Todd Meyerrose, Bruno Nervi, Michael Rettig, Jan A. Nolta, John F. DiPersio
Journal: Molecular Therapy (2004)

The survival, expansion and Graft versus Host Disease (GvHD) potential of human T cells in immunodeficient mouse models (SCID, SCID-Beige) have been limited by residual immune function and the need to inject large numbers of human T cells (>108–109) in conjunction with human antigen presenting cells into the peritoneal cavities of the animals. To overcome this problem, we used an immunodeficient mouse strain carrying the Beta 2 microglobulin knockout (NOD-SCID-β2M Null), which consistently permits survival, expansion, activation and GvHD potential of human T cells, even after intravenous (IV) injection of small numbers of enriched CD3/CD28 activated cells. In the current studies, T cells were isolated by Ficoll gradient centrifugation, and stimulated for 48 hours on immobilized antibodies to CD3 and CD28 in 24 well plates. Also, T cells transduced with a retroviral vector transferring a truncated CD34 receptor in conjunction with a Herpes Simplex Virus Thymidine Kinase (HSV TK) were prepared in the same way. FACS analyses of T cells pre-and post stimulation demonstrated up-regulation of stimulation markers (CD69 and CD25) after CD3/CD28 stimulation. Gene expressing human T cells were selected to a purity of over 90% using the Miltenyi magnetic bead separation system. A normal ratio of CD4+ and CD8+ cells and high viability was maintained during the culture period. Small numbers of cells (5–7×106 cells per mouse) were injected IV retro-orbitally, and the animals were followed for 4 weeks. Peripheral blood from the mice was analyzed on day 7, day 14, and day 30. The animals were sacrificed shortly after day 30 due to weight loss and clinical findings consistent with GvHD. Blood, spleen, liver, lymph nodes and other tissues were analyzed for the presence of human T cells. On day 7, human T cells (0.5–5%) could be detected in the peripheral blood of the mice. Human T cell numbers increased steadily over the follow up period, and high levels of human T cells (10–45%) could be measured on day 30. The T cell activation markers CD25 and CD69 were up-regulated. Gene transduced human T cells had also expanded in the same way in vivo and could be detected by FACS analysis via expression of the CD34 surface marker. Human CD3+ cells infiltrated the spleen, GI tract and other organs by day 30, coincident with the development of runting, weight loss and clinical findings consistent with GvHD. In summary, the NOD-SCID-β2M Null mouse provides a unique, efficient and consistent model to study gene transduced human T cell activation, expansion, survival and GvHD in a murine preclinical xenotransplantation model.
Fatality outside hospital from acute coronary events in three British health districts, 1994-5
Authors: R M Norris
Journal: BMJ (1998)

To provide a contemporary account of the treatment and outcomes of acute coronary attacks in England and Wales and to identify strategies that might improve the outcome.Two year community and hospital based study in three British health districts.Health districts of Brighton (population 282,000), South Glamorgan (408,000), and York (264,000).3523 men and women under 75 years of age who died outside hospital from acute coronary causes, who were admitted to hospital with acute myocardial infarction, or who developed acute infarction or died unexpectedly from acute coronary causes while they were already in hospital.Attempted resuscitation in people having a cardiac arrest outside hospital.Total case fatality, case fatality outside and inside hospital, and the effect of resuscitation on case fatality outside hospital.1589 patients died within 30 days of the acute event. Case fatality was 45% (95% confidence interval 43% to 47%), rising from 27% (160/595) (23% to 31%) at age < 55 years to 53% (1019/1916) (51% to 55%) at 65-74 years. Overall, 74% (1172/1589) (72% to 76%) of fatal events happened outside hospital, and there was a negative age gradient (P < 0.001) such that 91% (145/160) (87% to 95%) of fatalities occurred outside hospital at age < 55 compared with 70% (710/1019) (67% to 73%) at 65-74 years. Without successful resuscitation of 55 patients outside hospital, total case fatality at 30 days would have risen from 45% to 46.7%.Opportunities for reducing fatality from acute coronary attacks lie mainly outside hospital. These results and others imply that survival from cardiac arrest outside hospital might be trebled by improved ambulance and patient response. Proper application of secondary preventive measures for patients with coronary disease could have an even larger impact.
Abstract 18390: Ang II activates the RhoA Exchange Factor Arhgef1 in Humans
Authors: Maria-Luigia Carbone, Jérémy Brégeon, Nabila Devos, Anne Blanchard, Michel Azizi, Pierre Pacaud, Xavier Jeunemaitre, Gervaise Loirand
Journal: Circulation (2014)

Introduction: Although a causative role for RhoA-Rho kinase signaling has been recognized in the development of human hypertension, the molecular mechanism(s) as well as the RhoA exchange factors (GEFs) responsible for the over activation of RhoA remain unknown. Arhgef1 has been recently identified as a RhoA GEF involved in Ang II-mediated regulation of vascular tone and hypertension in mice. Hypothesis: Here we assessed the hypothesis that Arhgef1 is activated and involved in the activation of RhoA-Rho kinase signaling by Ang II in humans. Methods: We used in vitro stimulation of human coronary artery smooth muscle cells and human peripheral blood cells (PBMC) by Ang II (0.1 μmol/L), and PBMC isolated from normotensive subjects before and after activation of the renin-angiotensin system by a low-salt diet for 7 days (checked by the increase in plasma aldosterone and active renine). Activation of Arhgef1 was monitored by measuring its tyrosine phosphorylation by western blot and phosphorylation of the Rho kinase target MYPT was used to measure the activity of RhoA/Rho kinase signaling. Results: In vitro, Ang II induced activation of Arhgef1 in human vascular smooth muscle cells and PBMC. Silencing of Arhgef1 expression by siRNA in human vascular smooth muscle cells inhibited Ang II-induced activation of RhoA-Rho kinase signaling (0.67±0.12 vs 3.21±0.91relative to unstimulated condition, n=4, P&lt;0.05). In normotensive subjects, activation of the renin-angiotensin system by a low-salt diet stimulated Arhgef1 activity in PBMC (1.26±0.12-fold over basal level, n=39, P&lt;0.05). This activation was associated with an increase activity of RhoA-Rho kinase signaling (1.33±0.14-fold over basal level, n=39, P&lt;0.05). Conclusions: Our results show that Ang II stimulates Arhgef1 activity and strongly suggest that Arhgef1 mediates Ang II-induced RhoA activation in humans. Moreover, we show for the first time that measurement of RhoA GEF activity in PBMC might be a useful method to evaluate RhoA GEF activity in humans.
531. Activation of VEGF by Engineered Zinc Finger Transcriptional Activators: A Novel Therapeutic Approach to Diabetic Neuropathy
Authors: Carolyn L. Dent, Gabriel Lau, Edward J. Rebar, Lei Zhang, YaLi Lee, Andrew C. Jamieson, Casey C. Case, Tyler Martin, Philip D. Gregory
Journal: Molecular Therapy (2004)

Zinc finger protein transcription factors (ZFP TFs) can be engineered to regulate expression of any endogenous target gene, and thus represent a novel approach to the treatment of disease. In the area of diabetic neuropathy, for example, where no current treatment options are available, ZFP TF technology offers a unique solution to an unmet medical need.
Temporary Artificial Lung
Authors: Brian Vastag
Journal: JAMA (2001)

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
Folate and Nitrate-Induced Endothelial Dysfunction
Authors: Joseph Loscalzo
Journal: Circulation (2001)

rganic nitrates have served as mainstays of therapy for the treatment of coronary artery disease for more than a century.Their use, however, has been complicated by unwanted side effects, including hypotension and the development of nitrate tolerance.Nitrate tolerance is a term used to define tachyphylaxis to nitrates with long-term use.The mechanisms of nitrate tolerance have been debated for some time and include depletion of thiols, an increase in venous blood volume limiting vasodilator responsiveness, and increased generation of reactive oxygen species.
The puzzle of cooperationGenetic and Cultural Evolution of Cooperation edited by Peter Hammerstein. MIT Press, 2003. E29.95 hbk (xxiii + 450 pages) ISBN 0262083264. Foundations of Human Sociality: Economic Experiments and Ethnographic Evidence from Fifteen Small-Scale Societies edited by Joseph Henrich, Robert Boyd, Samuel Bowles, Colin Camerer, Ernst Fehr and Herbert Gintis. Oxford University Press, 2004. E55.00 hbk, E16.99 pbk (xiv + 320 pages) ISBN 0 19926204 7/0- 19 926205 5
Authors: T WENSELEERS
Journal: Trends in Ecology & Evolution (2004)
Shaping the Repertoire of Cytotoxic T-Lymphocyte Responses: Explanation for the Immunodominance Effect Whereby Cytotoxic T Lymphocytes Specific for Immunodominant Antigens Prevent Recognition of Nondominant Antigens
Authors: Stéphane Pion, Gregory J. Christianson, Pierre Fontaine, Derry C. Roopenian, Claude Perreault
Journal: Blood (1999)
Abstract 4381: MiR-205 and Trastuzumab: Potential as adjuvant therapeutic tool and predictive biomarker
Authors: Elvira D'Ippolito, Claudia Piovan, Ilaria Plantamura, Marta Giussani, Patrizia Casalini, Manuela Campiglio, Elda Tagliabue, Marilena V. Iorio
Journal: Cancer Research (2014)

Abstract Despite the improvement in the management of HER2+ breast cancer patients with the approval of Trastuzumab in the clinical practise, and the success rate of this treatment, a still considerable percentage of patients do not respond or eventually develop a secondary resistance, leading to relapse and poor outcome. A crucial issue is represented by the urgent need of biomarkers able to predict the response to treatment, and certainly of new therapeutic tools to counteract the resistance mechanisms. It is known that resistance to anti-HER2 therapies can be due to escape mechanisms triggered by alternative receptors: here we show that HER3 silencing, either mediated by miR-205, known to directly target the receptor (Iorio MV et al., 2009) or by a siRNA specific against HER3, is able to improve the responsiveness to Trastuzumab, reducing tumor cell growth and colony formation capability. This effect seems to be mediated by impairment of the Akt-mediated pathway. Finally, evaluating miR-205 expression in a series of 51 HER2+ breast cancer patients treated with Trastuzumab in adjuvant setting, we observed that miR-205 is significantly associated with outcome: setting the median expression as cut-off, and performing a contingency analysis (Fisher's exact test), miR-205 expression was above the median in a significantly (p=0.03) higher percentage of responders versus non responders patients (61% versus 26%). In summary, here we show that miR-205 improves the responsiveness to Trastuzumab treatment at least partially though HER3 silencing, and associated to outcome of patients treated in adjuvant setting, thus representing a potential adjuvant tool and predictive biomarker. Citation Format: Elvira D'Ippolito, Claudia Piovan, Ilaria Plantamura, Marta Giussani, Patrizia Casalini, Manuela Campiglio, Elda Tagliabue, Marilena V. Iorio. MiR-205 and Trastuzumab: Potential as adjuvant therapeutic tool and predictive biomarker. [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 4381. doi:10.1158/1538-7445.AM2014-4381
Abstract 14873: Is There Difference in Clinical Outcomes Following Percutaneous Coronary Intervention (PCI) for Acute Coronary Syndrome (ACS) between Hospitals With and Without Onsite Cardiac Surgery Backup?
Authors: Tomonori Akasaka, Seiji Hokimoto, Noriaki Tabata, Kenji Sakamoto, Kenichi Tsujita, Sunao Kojima, Koichi Kaikita, Hisao Ogawa
Journal: Circulation (2014)

Background: Based on 2011 ACCF/AHA/SCAI PCI guideline, it is recommended that PCI should be performed at hospital with onsite cardiac surgery. But, recent data suggests that there is no significant difference in clinical outcomes following primary or elective PCI between hospitals with and without onsite cardiac surgery. The proportion of PCI centers without onsite cardiac surgery comprises approximately more than half of all PCI centers in Japan. We examined the impact of with or without onsite cardiac surgery on clinical outcomes following PCI to ACS. Methods: From Aug 2008 to March 2011, subjects (n=2288) were enrolled from the Kumamoto Intervention Conference Study (KICS), which is a multicenter registry, and enrolling consecutive patients undergoing PCI in 15 centers in Japan. Patients were assigned to two groups treated in hospitals with (n=1954) or without (n=334) onsite cardiac surgery. Clinical events were followed up for 12 months. Primary endpoint was in-hospital death, cardiovascular death, myocardial infarction, and stroke. And we monitored other events those were non-cardiovascular deaths, bleeding complications, revascularizations, and emergent CABG. Results: There was no overall significant difference in primary endpoint between hospitals with and without onsite cardiac surgery (9.6%vs9.5%; P=0.737). There was also no significant difference when events in primary endpoint were considered separately. In other events, only revascularization was more frequently seen in hospitals with onsite cardiac surgery (22.1%vs12.9%; P&lt;0.001). Kaplan-Meier analysis for primary endpoint showed that there was no significant difference between two groups (Log Rank P=0.943). By cox proportional hazards model analysis for primary endpoint, without onsite cardiac surgery was not a predictive factor for primary endpoint (HR 0.969, 95%CI 0.704-1.333; P=0.845). We performed propensity score matching analysis to correct for the disparate patient numbers between two groups, and there was also no significant difference for primary endpoint (6.9% vs 8.0%; P=0.544). Conclusions: There is no significant difference in clinical outcomes following PCI for ACS between hospitals with and without onsite cardiac surgery backup in Japan.
Changes in lung mechanics and gas exchange in patients with pulmonary sarcoidosis (PS)
Authors: Marina Kameneva, Darya Syrtsova, Olga Baranova, Alexandra Speranskaya, Olga Yuryeva, Artem Tishcov
Journal: European Respiratory Journal (2014)

Aim: To investigate the type and degree of pulmonary mechanics and gas exchange in patients with different stages of PS.

Materials and methods: 129 cases of PS were analyzed: 48 male (mean age 38 SD 11 yr) and 81 female (mean age 50 SD 10 yr). All patients underwent lung function tests: spirometry, body plethysmography, compliance, diffusion capacity measurement, blood gases.

Results: Average values of all function parameters in the group of patients with the 1 stage of the PS (n=21) were normal, but individual analysis showed a reduction in diffusion capacity in 8 patients (38%). For the 2 stage (n=59) also had no change in characteristic parameters of pulmonary mechanics, but reduction of diffusion capacity have been observed in 50% of cases (76 SD 12 %pred). For the 3 stage (n=37) was characterized by reduction of diffusion capacity (70 SD 16 %pred) and increase of lung elastic recoil (CR=0.70 SD 0.25 kPa/l). The greatest changes were observed at the 4 stage (n=12): FEV1/VC (0.65 SD 0.12Pred), diffusion capacity (56 SD 19 %pred), TLC (79 SD 14%pred) decreased and CR (0.73 SD 0.34 kPa/l) increased, a mixed type of ventilation disorders was formed.

Conclusion: Reduction of lung diffusion capacity precedes the appearance of ventilation disorders and is the earliest functional sign of PS. Changes in pulmonary mechanics are the features of the later stages of PS. The parameters of lung elasticity change first, meaning a disease progression. The predominant type of ventilation disorders is mixed.
The Effect of Estrogens and a Carcinogenic Chemical in Stimulating the Secretion of the Mammogenic Duct Growth Factor of the Anterior Pituitary
Authors: A. A. Lewis, C. W. Turner
Journal: Cancer Research (1941)

When estrogens are injected into normal immature and castrated male or female animals growth of the duct system of the mammary gland is stimulated. During the past several years increasing evidence has accumulated indicating that this mammary hyperplasia is due not to a direct action of estrogen upon the mam- mary gland but instead to an increased rate of secretion of anterior pituitary hormones which have been called mammogen (17, 23, i8). Data recently published 1 indicate that this consists of 2 factors: a duct- growth factor and a lobule-alveolar-growth factor. A technic for the biological assay of the mammogenic duct-growth factor, in which young male mice are used, has been described (22). This method has now been extensively employed in assaying the mammogen content of pituitaries from dairy and beef cattle during several stages of growth, the sexual cycle, pregnancy, and lactation (23). The object of the present paper is to describe how this same assay technic may be used to advantage in the direct determination of the ability of various estro- genic chemicals to stimulate the secretion of mam- mogen (duct factor) by the pituitary. Such informa- tion is not only of interest as indicating the relative effectiveness on mammary hyperplasia of various types of chemical compounds which have estrogenic effects, but has a far greater value in measuring the effect of carcinogenic chemicals upon the secretion of mam- mogen. Lacassagne (21), Gardner, (i3, i4), and others (I) have shown that the injection of estrogens into male mice of cancer-susceptible strains will induce the formation of mammary tumors. As mammary growth is a prerequisite for mammary tumor formation, it would appear that the direct cause of such tumors is the secretion of mammogen by the pituitary rather
Abstract P085: Infant Weight and Length Trajectories Have Different Impacts on Body Composition at Age 3
Authors: Jessica G Woo, Heidi Sucharew, Patricia M Herbers, Philip R Khoury, Nicholas M Edwards, Heidi J Kalkwarf
Journal: Circulation (2014)

Introduction: Rapid infant weight gain has been linked with higher childhood body mass index (BMI) and risk of obesity. However, because BMI cannot distinguish lean from fat mass, the role of infant weight or length trajectories on childhood body composition is unclear. Hypothesis: This study aimed to evaluate how specific aspects of infant growth trajectories are associated with fat mass, lean mass and % body fat at age 3. Methods: Total 323 children age 3 y (46% female, 20% African-American) had body composition measured by dual-energy x-ray absorptiometry, and weight and length measurements from birth to age 2 y from pediatrician growth charts. Growth trajectories were characterized using the SuperImposition by Translation And Rotation (SITAR) model. This technique estimates an average growth curve with random effects that allow individual growth curves to shift up or down (size), shift right or left on the age axis (tempo) or rotate to steepen/flatten the growth curve (velocity). Tempo did not improve model fit so was excluded. Size and velocity parameters for weight and length trajectories were regressed against fat mass (FM), lean mass (LM) and % body fat measurements at age 3. Results: On average, girls had higher FM (3.9 vs. 3.4 kg) and lower LM (8.8 vs. 9.5 kg) than boys. Adjusting for sex, LM at age 3 was significantly higher with greater weight velocity and with longer length size between ages 0-2 (Table), but were not related to length velocity or weight size. Adjusting for sex, higher FM was seen for those with higher weight size between ages 0-2, but was not related to either weight or length velocities. Percent body fat at age 3 was associated with both larger weight size and shorter length size between 0-2 years of age, but not with either growth velocities. Conclusions: Weight and length size and velocity differ in their impact on children’s body composition by age 3. This study suggests that faster early weight gain (higher weight velocity) and longer lengths but not higher overall weight may lead to leaner body composition by age 3.
Proposed Legislation Seeks to Reform Mental Health Care
Authors: Laura Buchholz
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
FcγRIIA requires a Gi-dependent pathway for an efficient stimulation of phosphoinositide 3-kinase, calcium mobilization, and platelet aggregation
Authors: Marie-Pierre Gratacap, Jean-Pascal Hérault, Cécile Viala, Ashraf Ragab, Pierre Savi, Jean-Marc Herbert, Hugues Chap, Monique Plantavid, Bernard Payrastre
Journal: Blood (2000)
844. Novel Pathways of Cell Entry and Trafficking Utilized by Ad Capsid Proteins in the Absence of the Whole Virus
Authors: Altan Rentsendorj, Hasmik Agadjanian, Maguire Meghan, Jiansong Xie, Xinhua Chen, Michelle MacVeigh, Hamm-Alvarez Sarah, Lali K. Medina-Kauwe
Journal: Molecular Therapy (2004)

Cellular infection by Adenovirus serotype 5 (Ad5) is mediated by the viral capsid fiber and penton proteins. Whereas the fiber initiates high affinity binding to cellular Coxsackievirus Adenovirus Receptor (CAR) proteins, the penton binds to secondary integrin receptors, triggering receptor-mediated endocytosis of the virus. We have previously demonstrated that recombinant soluble penton proteins can assemble with plasmid DNA and deliver a reporter gene into cultured cells in the absence of the whole virus.