tbuckley/cabot-search huggingface dataset:
In vivo gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation
Authors: Vikas Hegde, Robyn P. Hickerson, Sitheswaran Nainamalai, Paul A. Campbell, Frances J.D. Smith, W.H. Irwin McLean, Deena M. Leslie Pedrioli
Journal: Journal of Controlled Release (2014)

Therapeutics based on short interfering RNAs (siRNAs), which act by inhibiting the expression of target transcripts, represent a novel class of potent and highly specific next-generation treatments for human skin diseases. Unfortunately, the intrinsic barrier properties of the skin combined with the large size and negative charge of siRNAs make epidermal delivery of these macromolecules quite challenging. To help evaluate the in vivo activity of these therapeutics and refine delivery strategies we generated an innovative reporter mouse model that predominantly expresses firefly luciferase (luc2p) in the paw epidermis--the region of murine epidermis that most closely models the tissue architecture of human skin. Combining this animal model with state-of-the-art live animal imaging techniques, we have developed a real-time in vivo analysis work-flow that has allowed us to compare and contrast the efficacies of a wide range nucleic acid-based gene silencing reagents in the skin of live animals. While inhibition was achieved with all of the reagents tested, only the commercially available "self-delivery" modified Accell-siRNAs (Dharmacon) produced potent and sustained in vivo gene silencing. Together, these findings highlight just how informative reliable reporter mouse models can be when assessing novel therapeutics in vivo. Using this work-flow, we developed a novel clinically-relevant topical formulation that facilitates non-invasive epidermal delivery of unmodified and "self-delivery" siRNAs. Remarkably, a sustained >40% luc2p inhibition was observed after two 1-hour treatments with Accell-siRNAs in our topical formulation. Importantly, our ability to successfully deliver siRNA molecules topically brings these novel RNAi-based therapeutics one-step closer to clinical use.
Global Public Health: Targeting Inequities
Authors: William H. Foege
Journal: JAMA (1998)

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
MUC1 Is a Counter-Receptor for Myelin-Associated Glycoprotein (Siglec-4a) and Their Interaction Contributes to Adhesion in Pancreatic Cancer Perineural Invasion
Authors: Benjamin J. Swanson, Kimberly M. McDermott, Pankaj K. Singh, John P. Eggers, Paul R. Crocker, Michael A. Hollingsworth
Journal: Cancer Research (2007)

Abstract Perineural invasion in pancreatic adenocarcinoma, a common pathologic phenomenon whereby cancer cells invade and intimately contact the endoneurium of pancreatic nerves, is thought to contribute to both pain and local disease recurrence. MUC1, a type I transmembrane mucin that can affect the adhesive properties of cells, contains a large extracellular tandem repeat domain, which is heavily glycosylated in normal epithelia, but is overexpressed and differentially glycosylated in pancreatic cancer. This altered glycosylation includes the shortened core I O-glycans for monosialyl and disialyl T antigens. Myelin-associated glycoprotein (MAG), a membrane-bound protein expressed on oligodendrocytes and Schwann cells, binds myelin to neurons. MAG's preferred ligands are derivatives of the monosialyl and disialyl T antigen. We investigated whether MUC1 is a counter-receptor for MAG and if their interaction contributed to pancreatic perineural invasion. Results showed that MAG binds pancreatic cells expressing MUC1, that this binding is sialidase-sensitive, and that MAG physically associates with MUC1. Heterotypic adhesion assays between pancreatic cancer cells and Schwann cells revealed that increased expression of MUC1 or MAG enhanced adhesion. Conversely, specific inhibition of MAG or sialyl-T MUC1 partially blocked adhesion. Immunohistochemical analysis of pancreatic perineural invasion showed the expression of both MUC1 and MAG. These results support the hypothesis that the adhesive interactions between MUC1 and MAG are of biological significance in pancreatic cancer perineural invasion. [Cancer Res 2007;67(21):10222–9]
Inadequate T follicular cell help impairs B cell immunity during HIV infection
Authors: Rafael A Cubas, Joseph C Mudd, Anne-Laure Savoye, Matthieu Perreau, Julien van Grevenynghe, Talibah Metcalf, Elizabeth Connick, Amie Meditz, Gordon J Freeman, Guillermo Abesada-Terk, Jeffrey M Jacobson, Ari D Brooks, Shane Crotty, Jacob D Estes, Giuseppe Pantaleo, Michael M Lederman, Elias K Haddad
Journal: Nature Medicine (2013)
Comparative evaluation of establishing a human gut microbial community within rodent models
Authors: Melissa L. Wos-Oxley, André Bleich, Andrew P.A. Oxley, Silke Kahl, Lydia M. Janus, Anna Smoczek, Hannes Nahrstedt, Marina C. Pils, Stefan Taudien, Matthias Platzer, Hans-Jürgen Hedrich, Eva Medina, Dietmar H. Pieper
Journal: Gut Microbes (2012)

The structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of different diseases. Establishing a defined human gut microbial community within inbred rodent models provides a means to study microbial-related pathologies, however, an in-depth comparison of the established human gut microbiota in the different models is lacking. We compared the efficiency of establishing the bacterial component of a defined human microbial community within germ-free (GF) rats, GF mice and antibiotic-treated specific pathogen-free mice. Remarkable differences were observed between the different rodent models. While the majority of abundant human-donor bacterial phylotypes were established in the GF rats, only a subset was present in the GF mice. Despite the fact that members of the phylum Bacteriodetes were well established in all rodent models, mice enriched for phylotypes related to species of Bacteroides. In contrary to the efficiency of Clostridiales to populate the GF rat in relative proportions to that of the human-donor, members of Clostridia cluster IV only poorly colonize the mouse gut. Thus, the genetic background of the different recipient rodent systems (that is, rats and mice) strongly influences the nature of the populating human gut microbiota, determining each model's biological suitability.
HEART DISEASE AMONG ADOLESCENT SCHOOL CHILDREN OF NEW YORK CITY
Authors: MORRIS GOODMAN
Journal: JAMA (1934)

In a recent communication we reported the organization, procedure and method of examination of the Diagnostic Cardiac Clinic of New York City. 1 The present report deals with an analysis of some of the data accumulated in the twenty-seven months of the clinic's existence. This includes data on the prevalence of cardiac abnormalities and organic heart disease among adolescent school children. The problems bearing on the school child with heart disease, including medical supervision and early diagnosis, are discussed. In the period between Oct. 1, 1930, and Dec. 31, 1932, 166,152 children applied for working certificates in New York City. Of that number only 109,964 could be included in this analysis, because the children diagnosed as having cardiac abnormalities among the remaining 56,188 were not referred to the clinic for complete cardiac study. The great majority of these children were in the age group between 14 and 17 years and
Social Phobia—Not Just Another Name for Shyness
Authors: Lynne Lamberg
Journal: JAMA (1998)

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
Preparation of I-131-labeled human serum prealbumin and its metabolism in normal and sick patients.
Authors: E L Socolow, K A Woeber, R H Purdy, M T Holloway, S H Ingbar
Journal: Journal of Clinical Investigation (1965)

Despite some early doubts concerning its presence in plasma and its physiological function (1-4), the thyroxine-binding prealbumin of human serum (TBPA) is now known to play a significant role in the transport of thyroxine (T4) (5-8).Nor- mally, as assessed by in vitro techniques, TBPA appears to bind at least 25 to 35%o of T4 in serum (5, 6).In the serum of many patients with se- vere acute or chronic illness, however, the propor- tion of endogenous T4 in serum bound by TBPA and the T4-binding capacity of TBPA decline (8,9).The recent availability of substantial quanti- ties of a highly purified preparation of TBPA has made possible an investigation of the in vivo me- tabolism of this protein in normal patients and in patients with a variety of disorders that lead to de- creased binding of T4 by TBPA in serum.In ad- dition, the cause of this decrease in T4 binding in the serum of such "sick" patients has been evalu- ated.A portion of the findings has been presented in abstract form (10).While these studies were in progress, Oppenheimer, Surks, Bernstein, and Smith reported similar studies in abstract form (11, 12). MethodsHighly purified TBPA was prepared from plasma Fraction IV-6 (method 6) of Cohn and colleagues (13).
High-Avidity T Cells Are Preferentially Tolerized in the Tumor Microenvironment
Authors: Ziqiang Zhu, Vinod Singh, Stephanie K. Watkins, Vincenzo Bronte, Jennifer L. Shoe, Lionel Feigenbaum, Arthur A. Hurwitz
Journal: Cancer Research (2012)

Abstract One obstacle in eliciting potent antitumor immune responses is the induction of tolerance to tumor antigens. TCRlo mice bearing a TCR transgene specific for the melanoma antigen tyrosinase-related protein-2 (TRP-2, Dct) harbor T cells that maintain tumor antigen responsiveness but lack the ability to control melanoma outgrowth. We used this model to determine whether higher avidity T cells could control tumor growth without becoming tolerized. As a part of the current study, we developed a second TRP-2–specific TCR transgenic mouse line (TCRhi) that bears higher avidity T cells and spontaneously developed autoimmune depigmentation. In contrast to TCRlo T cells, which were ignorant of tumor-derived antigen, TCRhi T cells initially delayed subcutaneous B16 melanoma tumor growth. However, persistence in the tumor microenvironment resulted in reduced IFN-γ production and CD107a (Lamp1) mobilization, hallmarks of T-cell tolerization. IFN-γ expression by TCRhi T cells was critical for upregulation of MHC-I on tumor cells and control of tumor growth. Blockade of PD-1 signals prevented T-cell tolerization and restored tumor immunity. Depletion of tumor-associated dendritic cells (TADC) reduced tolerization of TCRhi T cells and enhanced their antitumor activity. In addition, TADCs tolerized TCRhi T cells but not TCRlo T cells in vitro. Our findings show that T-cell avidity is a critical determinant of not only tumor control but also susceptibility to tolerization in the tumor microenvironment. For this reason, care should be exercised when considering T-cell avidity in designing cancer immunotherapeutics. Cancer Res; 73(2); 595–604. ©2012 AACR.
Elevated stricture rate following the use of fully covered self-expandable metal biliary stents for biliary leaks following liver transplantation
Authors: M. Phillips, H. Bonatti, B. Sauer, L. Smith, M. Javaid, M. Kahaleh, T. Schmitt
Journal: Endoscopy (2011)

Background: Biliary leaks and strictures are common complications after liver transplantation and can be managed surgically or endoscopically. Endoscopic management using fully covered self-expandable metal stents (FCSEMS) might provide some advantages over the commonly used plastic stents in the management of bile leaks after liver transplantation.
The Transition From Phase II To Phase III Studies
Authors: Dominik R. Berthold, Aliya Gulamhusein, John I. Jackson, Ian F. Tannock
Journal: Journal of Clinical Oncology (2009)

monotherapy offers similar improvements in survival and PSA response rate as the docetaxel/estramustine combination. 5,6 One of the key messages of our trial is that estramustine phosphate significantly increases toxicity: more patients in the docetaxel/ estramustine group (45%) had at least one grade 3/4 toxicity compared with those who received docetaxel alone (21%; P ϭ .005). 1 The increase in toxicity is also suggested by the Fizazi et al 4 meta-analysis and the indirect comparisons between the Southwest Oncology Group 99-16 and the TAX 327 studies. 5,6 Although, we all believe in what we are doing for the patients with CRPC, we should not forget that we are dealing with palliative patients.These patients are old, with frequent comorbidities.The survival benefit provides by docetaxel remains modest. 5,6 "Primum non nocere" is one of the most important principle of antic and modern medicine, particularly in the case of palliative disease.In this context, we strongly believe that estramustine should not be used in combination with chemotherapy, based on the available data.Only a large randomized trial including several hundreds of patients could, maybe, show a small clinical benefit in favor of estramustine-based chemotherapy.Would it be relevant in regard of the quality of life of our patients?
Successful in-vitro fertilisation and embryo transfer after treatment with recombinant human FSH
Authors: Marc Germond, Salvatore Dessole, Alfred Senn, Ernest Loumaye, Colin Howles, Vanya Beltrami, Paul Devroey, Andre Van Steirteghem, Bernadette Mannaerts, Herjan Coelingh Bennink
Journal: The Lancet (1992)
Marjorie Olive Bennett (nee Dunster) Leonard Roy Griffiths Eric Bernard Grogono Dorothy Grace Hervey Frank Charles Naldrett ("Pat") Holden Howard Lloyd-Thomas Catherine Logan (nee Aicken) James Henry Miller Hartwin Siegfried Sadowski David Alexander Sime
Authors: J. Crossley, D Telford, A T Macheta, A. James, A. Grogono, D. Bowman, E. W. Jones, J. Lloyd-Thomas, R Logan, A. Conner, A. Stein, R. Graham, P. E Harris
Journal: BMJ (2000)
Haemodynamic adaptation two months after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients.
Authors: L A Colombato, L Spahr, J P Martinet, M P Dufresne, M Lafortune, D Fenyves, G Pomier-Layrargues
Journal: Gut (1996)

BACKGROUND AND AIMS: In portal hypertensive patients, transjugular intrahepatic portosystemic shunt (TIPS) acutely increases cardiac output and exaggerates peripheral vasodilatation. It has been suggested that the worsened hyperdynamic state may progress to high output heart failure. The aim was to evaluate the acute and short-term haemodynamic adaptation to this procedure. METHODS: Systemic, splanchnic, and pulmonary haemodynamics were studied in 15 cirrhotic patients under stable haemodynamic conditions before placement of TIPS, then 15-30 minutes after and two months later. For inclusion in the final analysis, an uneventful post-TIPS at two months follow up and a stable portacaval gradient were required. The following variables were measured or calculated: portacaval gradient; cardiac index (thermodilution); systolic and diastolic mean arterial, atrial, pulmonary arterial, and wedged pulmonary capillary pressures; heart rate; and total peripheral and pulmonary vascular resistances. Blood flow in the shunt was measured using duplex Doppler ultrasound. RESULTS: The portacaval gradient decreased by 56% and remained stable thereafter. Shunt blood flow was unchanged when measured immediately after TIPS and two months later. Immediately after TIPS there was a pronounced increase in cardiac index (+32%; p &lt; 0.05) in association with a decrease in peripheral and pulmonary vascular resistance (-21%; p &lt; 0.05 and -14%; NS). Two months later, whereas the initial rise in cardiac index was attenuated, peripheral vascular resistances remained similar and pulmonary vascular resistances decreased further (-33%; p &lt; 0.05) compared with immediate post-TIPS values. CONCLUSIONS: Hyperdynamic circulation worsened immediately after TIPS, with a progressive adaptation during follow up. The mechanisms of post-TIPS induced haemodynamic changes include an abrupt volume load resulting from splanchnic decompression and an increased delivery of gut derived vasodilators to the systemic circulation. The persistence of decreased peripheral and pulmonary vascular resistances despite the reduction in high cardiac output two months after TIPS suggests that vasodilatation is not solely a compensatory response to a TIPS induced increased preload. Vasodilatory substances shunted away from the liver probably play an important part in this phenomenon.
Abstract 2277: Autophagy-associated necroptosis contributes to cancer cell cytotoxicity induced by the chalcone compound SBC2
Authors: Weiyang He, Qiong Wang, Balasubramanian Srinivasan, Xiuling Xu, Wenshu Chen, Mabel T. Padilla, Xin Gou, Chengguo Xing, Yong Lin
Journal: Cancer Research (2012)

Abstract Chalcone-based compounds are potential agents for cancer chemoprevention and chemotherapy. The recently developed chalcone-based compound SBC2 suppresses xenograft tumor growth in nude mice, however, the mechanisms by which SBC2 kills cancer cells are elusive. In this study, we have investigated the cellular signaling pathways involved in SBC2's cytotoxicity in cancer cells derived from lung and bladder tumors. SBC2 potently killed different cancer cells, which was effectively blocked by the necroptosis inhibitor Necrostatin-1 and knockdown of the necroptosis pathway components RIP1 and RIP3, suggesting that SBC2-induced cytotoxicity is associated with necroptosis. SBC2 robustly activated JNK and ERK through activation of their upstream activating kinases MEKK1 and MKK7. Blocking JNK and ERK effectively blocked SBC2-induced cytotoxicity, implying an important role of these MAPKs in SBC2-induced cancer cell death. In addition, SBC2 strongly induced autophagy, which was suppressed when JNK was blocked. Furthermore, SBC2 triggered BCL-XL phosphorylation that was dependent on JNK. Importantly, suppression of autophagy with either pharmacological inhibitors or a siRNA targeting the essential autophagy component ATG7 effectively attenuated SBC2-induced cell death. These results suggest that SBC2 kills cancer cells through activating JNK-mediated and autophagy-associated necroptosis. Taken together, our observations substantiate SBC2 as a potential anticancer therapeutic and identify a novel pathway for cancer cell killing by SBC2 that involves autophagy and necroptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2277. doi:1538-7445.AM2012-2277
Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1, and vascular cell adhesion molecule type 1.
Authors: M C Cid, H K Kleinman, D S Grant, H W Schnaper, A S Fauci, G S Hoffman
Journal: Journal of Clinical Investigation (1994)

Adhesion of leukocytes to endothelial cells is a critical step in the development of acute and chronic inflammatory lesions. We report here that estradiol treatment of cultured human umbilical vein endothelial cells stimulated up to a twofold increase in TNF-induced adhesion of both polymorphonuclear leukocytes and PMA-activated peripheral blood mononuclear cells. This effect was more evident (threefold increase) when endothelial cells were cultured on the basement membrane glycoprotein laminin. Progesterone, but not testosterone, had a similar stimulatory effect. Estradiol also promoted a slight increase in interferon gamma-stimulated endothelial cell adherence for peripheral blood mononuclear cells, but no effect of estradiol was observed when adhesion of leukocytes to endothelial cells was stimulated with IL-1 or IL-4. The estradiol-induced increase in leukocyte binding to human umbilical vein endothelial cells was partially blocked by antibodies to the adhesion molecules E-selectin, intercellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1). Indirect immunofluorescence techniques showed that estradiol produces an increase in TNF-induced cell surface expression of these molecules. Northern blot analysis demonstrated a transient increase in TNF-induced expression of mRNA for E-selectin, ICAM-1, and VCAM-1 in endothelial cells treated with estradiol. Our data demonstrate that estradiol has important regulatory functions in promoting leukocyte-endothelial cell interactions that might contribute to the observed predominance in females of some autoimmune inflammatory diseases.
Segmental Reversal of Small Intestine After Massive Bowel Resection
Authors: L. Dean Gibson, Richard Carter, David B. Hinshaw
Journal: JAMA (1962)

EXTENSIVE small-bowel resections are most frequently performed for mesenteric vascular occlusion and volvulus. In 1880, Koeberle reported the first successful massive intestinal resection. When more than 200 cm., or approximately 7 ft., of small intestine is removed, the resection is generally considered to be massive. The immediate mortality is high and the majority of those who survive develop the short-bowel syndrome which often results in death. The term "short-bowel syndrome" refers to the clinical features of malabsorption such as diarrhea, steatorrhea, weight loss, anemia, hypocalcemia, hypomagnesemia, and hypoproteinemia. These features usually are not apparent if more than 100 cm. of normal upper small intestine remains, and it is rare for patients to recover with less than 50 cm. of proximal jejunum, but occasional survivors have been reported. When more than 80% of the small bowel is resected in the dog, cachexia and death within 90 days are the rule. However,