tbuckley/cabot-search huggingface dataset:
Genetic Targeting of the Active Transcription Factor XBP1s to Dendritic Cells Potentiates Vaccine-induced Prophylactic and Therapeutic Antitumor Immunity
Authors: Shenghe Tian, Zuqiang Liu, Cara Donahue, Louis D Falo, Zhaoyang You
Journal: Molecular Therapy (2011)

In vivo dendritic cells (DC) targeting is an attractive approach with potential advantages in vaccine efficacy, cost, and availability. Identification of molecular adjuvants to in vivo "modulate " DC to coordinately render improved Th1 and CD8 T cell immunity, and attenuated deleterious Treg effects, is a critical challenge. Here, we report that in vivo genetic targeting of the active transcription factor XBP1s to DC (XBP1s/DC) potentiated vaccine-induced prophylactic and therapeutic antitumor immunity in multiple tumor models. This immunization strategy is based on a genetic vaccine encoding both cytomegalovirus (CMV)-driven vaccine Aghsp70 and DC-specific CD11c-driven XBP1s. The novel targeted vaccine induced durable Th1 and CD8 T cell responses to poorly immunogenic self/tumor antigen (Ag) and attenuated tumor-associated Treg suppressive function. Bone marrow (BM)-derived DC genetically modified to simultaneously overexpress XBP1s and express Aghsp70 upregulated CD40, CD70, CD86, interleukin (IL)-15, IL-15Rα, and CCR7 expression, and increased IL-6, IL-12, and tumor necrosis factor (TNF)-α production in vitro. XBP1s/DC elevated functional DEC205(+)CD8α(+)DC in the draining lymph nodes (DLN). The data suggest a novel role for XBP1s in modulating DC to potentiate tumor vaccine efficacy via overcoming two major obstacles to tumor vaccines (i.e., T cell hyporesponsiveness against poorly immunologic self/tumor Ag and tumor-associated Treg-mediated suppression) and improving DEC205(+)CD8α(+)DC.
The role of extracellular polysaccharide substance produced by Staphylococcus epidermidis in miliaria
Authors: Christen M Mowad, Kenneth J McGinley, Arlene Foglia, James J Leyden
Journal: Journal of the American Academy of Dermatology (1995)

Previous studies have indicated that cutaneous bacteria, particularly coagulase-negative staphylococci, play a role in the pathogenesis of miliaria. An accumulation of periodic acid-Schiff (PAS)-positive material has been described as blocking the sweat duct in miliaria. Furthermore, a PAS-positive extracellular polysaccharide substance (EPS) has been identified as a product of some strains of Staphylococcus epidermidis.We evaluated the relative ability of various species of coagulase-negative staphylococci to induce miliaria with particular reference to the potential role of EPS.We inoculated various strains of coagulase-negative staphylococci on the volar forearms of subjects under an occlusive dressing coupled with thermal stimulation. Ability to induce miliaria as well as microbiologic, histologic, and immunostaining features were evaluated.Miliaria was induced only with strains of S. epidermidis; other species including S. haemolyticus, S. hominis, S. cohnii, S. saprophyticus, and S. simulans were not capable of inducing miliaria. Moreover, only S. epidermidis strains capable of producing EPS were capable of inducing miliaria.Our data indicate that EPS is the PAS-positive material that obstructs the delivery of sweat to the skin surface in miliaria and therefore demonstrate that the EPS produced by S. epidermidis plays a central role in the pathogenesis of miliaria. Furthermore, in a survey of staphylococcal flora isolated from 68 subjects, EPS-producing strains were found to be common.
Abstract P3-07-09: Prevalence and effects of off-label use of chemotherapeutic agents in elderly breast cancer patients: estimates from Surveillance, Epidemiology and End Results-Medicare data
Authors: AA Eaton, CS Sima, KS Panageas
Journal: Cancer Research (2012)

Abstract Purpose: To gain FDA approval, drug companies submit evidence from clinical trials demonstrating that a drug is safe and efficacious in a certain setting. Current regulations allow oncologists to prescribe approved drugs for uses other than those for which the drug was approved (off-label use). While there seems to be a consensus that off-label use is common in oncology, there is a lack of published data on recent trends and on utilization in different populations. The strength of evidence demonstrating safety and efficacy varies for drugs used in the off-label setting, and patients may be at risk for unacceptable toxicity. The risk of toxicity may be higher among older patients, whose ability to tolerate chemotherapy is compromised by age-related organ decline and comorbidities. Our objective was to describe the prevalence of off-label use of chemotherapeutic agents in elderly breast cancer patients with Medicare coverage and to compare toxicity between patients using off-label drugs and patients using only approved drugs. Materials and Methods: We identified women 65 and older with a first primary breast cancer diagnosed in 2000–2007 from Surveillance, Epidemiology and End Results (SEER) cancer registry data linked with Medicare claims. Specific chemotherapeutic agents used following diagnosis were identified in Medicare claims and classified as on- or off-label use based on whether the drug was approved for breast cancer as of May 2012. Thirty-day toxicity (ER visit, hospitalization or death) was compared between patients whose first line regimen contained only approved drugs and patients whose first line regimen contained at least one off-label drug using the Cochran-Mantel-Haenszel test. Results: The most commonly-used approved drugs were cyclophosphamide (used in 14% of patients), doxorubicin (10%), docetaxel (5%), fluorouracil (5%), and paclitaxel (5%). In total, forty-five off-label agents were used. Vinorelbine and carboplatin were each used in 1% of patients. No other off-label drug was used in more than 109 (0.11%) of patients. Toxicity was significantly higher for patients treated with off-label agents compared to patients treated with only approved drugs, after adjusting for stage at diagnosis (p = 0.01). Conclusions: In this population-based cohort, rates of chemotherapy use were generally low, and rates of off-label use were even lower, with only 3% of patients treated off-label. Off-label use became more common as stage at diagnosis increased, with use increasing from 1% in stage 0/1 patients to 12% in stage 4 patients. The higher toxicity rates observed in patients treated with off-label drugs may indicate that these drugs are less safe than approved agents. This result will be confirmed in a matched analysis accounting for age, stage and comorbidities. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-09.
Community Psychiatry and Emergency Service
Authors: DONALD A. SCHWARTZ, AUDREY T. WEISS, JAMES M. MINER
Journal: American Journal of Psychiatry (1972)

The psychiatric emergency service at the Orange County (Calif.) Medical Center provides emergency service for periods from one to two hours up to a day or more on the unit. Comparisons were made between patients seen only once over the first four months of operation and those seen more than once during that period. Patients with acute situational problems could be handled on a one-visit basis, often without hospitalization. Those with personality disorders (including alcohol and drug problems) came more frequently and were hospitalized more often.
Role of tumour necrosis factor (TNF) in host defence against tuberculosis: implications for immunotherapies targeting TNF
Authors: S Ehlers
Journal: Annals of the Rheumatic Diseases (2003)

Studies in mouse infection models clearly demonstrate tumour necrosis factor (TNF) to be a critical component of both the antibacterially protective and the inflammatory immune response to Mycobacterium tuberculosis. It is therefore not surprising that treatment of patients-for example, those with rheumatoid arthritis-with biological agents interfering with TNF activity have shown an increased risk of reactivating tuberculosis. However, conceivably, TNF targeting biological agents can be developed that because of their particular mode of action and their specific pharmacodynamics may be less likely to have this side effect.
Performance indicators for general practice
Authors: F A. Majeed, S. Voss
Journal: BMJ (1995)

Some family health services authorities are now producing performance indicators for the general practices they administer.1 2 3 With the move towards a primary care led NHS,4 5 these indicators will become an important management tool. League tables of practice performance are a possibility: for example, practices could be ranked by rates of uptake of cervical smear tests and the proportion of drugs prescribed generically. Many general practitioners, particularly those who work in deprived communities, will find this development threatening and may think that league tables will unfairly label their practice as performing poorly. Family health services authorities must therefore ensure that performance indicators are interpreted appropriately.6

Performance indicators may be used to identify and reward high performing practices with increased allocations for staff and premises. Conversely, if resources are allocated according …
Specificity of the FTA-ABS Test for Syphilis
Authors: Dan M. Mackey
Journal: JAMA (1969)

In this evaluation of the fluorescent treponemal antibody-absorption (FTA-ABS) test, special emphasis is placed on its specificity as opposed to sensitivity. Among a total of 827 persons tested, there were five with a reactive FTAABS test confirmed by the Control Laboratory, and a non-reactive<i>Treponema pallidum</i>immobilization test accompanied by no clinical or historical evidence of syphilis. These five persons represent 0.6% of the total tested and 1.4% of those with a reactive FTA-ABS test. Three of these patients had diseases in which abnormal globulins frequently are found—rheumatoid arthritis, autoimmune hemolytic anemia due to lymphosarcoma, and alcoholic cirrhosis; two had no recorded evidence of disease. All were more than 50 years of age. Whether these cases represent old syphilis or false positive reactions to the FTA-ABS test is problematical.
Re: Markus J. Bader, Christian Gratzke, Michael Seitz, et al. The “All-Seeing Needle”: Initial Results of an Optical Puncture System Confirming Access in Percutaneous Nephrolithotomy. Eur Urol 2011;59:1054–9
Authors: Jin-Yi Li, Zilian Cui, Xiao Feng Gao, Jun-yi Jiang, Tai-le Jing, Lei Shi, Yong-han Peng, Ying-hao Sun
Journal: European Urology (2011)
Hidden Ethical Issues in Clinical Decision Analysis
Authors: Allan S. Brett
Journal: New England Journal of Medicine (1981)

In recent years, decision analysis has been increasingly advocated as a means of solving complicated clinical problems. These problems tend to involve numerous variables that must be carefully weighed before a solution can be proposed. For example, an article demonstrating the application of decision analysis to renal vasculitis and stomach ulcerations recently appeared in the Journal. 1 The rationale for using this method is that intuitive answers to clinical problems may not always be the most accurate. Instead, a decision tree is constructed that incorporates known values about disease frequency, disease mortality and morbidity, treatment toxicity, and accuracy and ill . . .
Abstract 1756: Downregulation of topoisomerase IIα by all-<i>trans</i> retinoic acid in human cervical carcinoma cells
Authors: Xiaoting Li, Shilong Fu, XIn Shen, Donghu Zhou, Apei Jiang, Suping Han, Qing Feng
Journal: Cancer Research (2012)

Abstract Cervical cancer remains a threatening disease to women worldwide. Topoisomerase IIα is a novel proliferation marker for cervical cancer diagnosis, therapy and prognosis. Understanding of the regulation of topoisomerase IIα would facilitate prevention and therapy of cervical cancer. In the present study, a significant repression of topoisomerase IIα level in stage Ib of squamous cervical carcinoma tissue was observed in patients with chemotherapeutic treatment, suggesting topoisomerase IIα is a target for chemotherapeutic drugs. All-trans-retinoic acid (ATRA), a chemopreventive agent, was shown to suppress both endogenous and exogenous topoisomerase IIα protein but not mRNA expression in human cervical carcinoma HeLa cells. Cycloheximide (CHX) prior to ATRA treatment augmented the topoisomerase IIα instability. ATRA induced the degradation of topoisomerase IIα via the proteasome pathway but not lysosome pathway. Ubiquitination was involved in this ATRA-induced topoisomerase IIα degradation. The ATRA-induced topoisomerase IIα repression occurred only in cell nucleus. Interestingly, overexpression of topoisomerase IIα enhanced cyclin D1 expression and caused HeLa cells de-differentiation while knockdown of topoisomerase IIα resulted in the cells differentiation and decreased cyclin D1. ATRA suppressed drug resistant protein P-gp while the typical topoisomerase II inhibitor etoposide did not. The molecular therapeutic implication of ATRA in cervical cancer therapy is discussed. 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 1756. doi:1538-7445.AM2012-1756
Proximal stomach and antrum in stomach emptying.
Authors: M C Barker, I Cobden, A T Axon
Journal: Gut (1979)

In a series of measurements of liquid-phase gastric emptying using a radionuclide marker on 35 subjects, five were identified in whom the proximal stomach and antrum were clearly distinguishable. Three of these subjects were normal controls and two suffered from systemic sclerosis. In the three normal subjects, analysis of the movement of the liquid showed the expected movement from fundus to antrum and thence through the pylorus. In the two patients with systemic sclerosis, there was, in contrast, evidence of mass retropulsion of the contents of the antrum into the fundus. In such cases, the measurement of stomach emptying based on the assumption of a single-compartment system in likely to be misleading.
Abstract 4995: Role of MICAL1 in NEDD9 invasive signaling
Authors: Casey O. Holmes, Amanda M. Brock, Philip T. Sobash, Jessica A. Tiedeken, Steven A. Rosenzweig
Journal: Cancer Research (2014)

Abstract Metastasis is the final step leading to patient death in most solid tumors, including head and neck squamous cell carcinoma (HNSCC). For metastasis to proceed, tumor cells must become mobile and invasive, losing their communal behavior. A goal of our work is to delineate the downstream effectors of growth factor signaling pathways that contribute to invasion. Using a phosphotyrosine proteomics screen we previously identified neural precursor cell expressed, developmentally down-regulated 9 (NEDD9; CasL) as a mediator of VEGF and IGF-1 signaling to invasion in HNSCC cells. NEDD9 tyrosine phosphorylation led to matrix metalloproteinase9 (MMP9) expression and secretion, invadopodia formation and enhanced invasion. To determine the molecular details of NEDD9 protein:protein interactions leading to invasion, we have generated a series of NEDD9 substrate domain tyrosine (Y to F, YXXP) and SH3 domain mutants. Mutation of all 13 YXXP motifs to FXXP blocked NEDD9 tyrosine phosphorylation, MMP9 expression and invadopodia formation. Of note, we found that NEDD9 co-immunoprecipitated with Molecule Interacting with CasL 1 (MICAL1). To further define this interaction and its downstream impact, stable NEDD9 or MICAL1 silenced HNSCC cell lines expressing select shRNAs were generated, with each exhibiting reduced migration and invasion. MICAL shRNA transfected cell lines also exhibited decreased MMP9 secretion, consistent with our findings that lack of MICAL1 decreases cell invasion and with findings of other labs that MICALs interact with Rab proteins altering intracellular trafficking. Further, we have verified that MICAL1 and NEDD9 form complexes in cells based on coimmunoprecipitation analyses. Better understanding of this pathway will undoubtedly lead to the identification of novel therapeutics for the prevention of invasion and metastasis. Supported by NIH R01CA134845 (SAR), P30 CA138313 and NIH/NCRR UL1 TR000062/TL1 TR000061 from the South Carolina Clinical &amp; Translational Research Institute (COH). Citation Format: Casey O. Holmes, Amanda M. Brock, Philip T. Sobash, Jessica A. Tiedeken, Steven A. Rosenzweig. Role of MICAL1 in NEDD9 invasive signaling. [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 4995. doi:10.1158/1538-7445.AM2014-4995
Supermarket offers allergy tests
Authors: O. Dyer
Journal: BMJ (1996)

A British general practitioner is facing finan- cial ruin from crippling legal costs more than five years after winning a High Court slander action against his former partner.Dr Malcolm Smith made legal history in October 1991 when he won record slander damages of 1 50 000 ($225 000) and costs estimated at 1 60 000 ($240 000) from Dr Alanah Houston.Dr Houston, who practised from the same premises as Dr Smith, had accused him of groping her and her staff.But Dr Houston declared herself bank- rupt within two months of the judgment.Now Dr Smith, who has had his house repos- sessed and has been forced to leave his practice through inability to pay the running costs, is facing action by his solicitor to enforce a 184 000 ($276 000) bill for costs -plus interest, which is mounting daily.The saga is a cautionary tale for those tempted to invoke the law to right a wrong.Yet as Dr Smith saw it, he had no choice because the accusation could have spelt professional ruin.The case has already cost him nearly 100 000 ($150 000); his father mortgaged his house to help raise the legal fees.After the court judgment, Dr Smith's solicitor, Thomas Watts, clocked up another £120 000 ($180 000) in fees.Mr Watts said that these were incurred in dealing with the media, preparing to fight an appeal by Dr Houston (at which, in the end, Dr Smith rep- resented himself), attempting to enforce the judgment against her, and fighting an appli- cation by her to force the sale of the jointly owned health centre in Northampton.The appeal court reduced the damages to £50 000 ($75 000), but Dr Smith received only £1 000 ($1500) after the trustee in bank- ruptcy's legal costs, which absorbed nearly all Dr Houston's 130 000 ($195 000) assets.Last week Dr Smith was in court again, this time battling against his solicitor.He wants to appeal against the bill but has been ordered to give "security for costs"-a charge overt his only remaining asset, the mortgaged health centre property, to ensure that his opponent will be paid his costs if Dr Smith loses.The appeal court upheld the ruling.Dr Smith's 1800 patients are still registered in his name, but they are looked after by locums.According to him, the practice is losing money, and he lives on "the charity of my family."The case has become a "full time job.
The collagen lattice: a model for studying the physiology, biosynthetic function and pharmacology of the skin
Authors: B. COULOMB, L. DUBERTET, C. MERRILL, R. TOURAINE, E. BBLL
Journal: British Journal of Dermatology (1984)

Journal Article The collagen lattice: a model for studying the physiology, biosynthetic function and pharmacology of the skin Get access B. COULOMB, B. COULOMB Laboratoire de Dermatologie, Hôpital Henri Mondor,94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar L. DUBERTET, L. DUBERTET Laboratoire de Dermatologie, Hôpital Henri Mondor,94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar C. MERRILL, C. MERRILL Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachussets. U. S. A. Search for other works by this author on: Oxford Academic Google Scholar R. TOURAINE, R. TOURAINE Laboratoire de Dermatologie, Hôpital Henri Mondor,94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar E. BBLL E. BBLL Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachussets. U. S. A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s27, 1 July 1984, Pages 83–87, https://doi.org/10.1111/j.1365-2133.1984.tb15585.x Published: 01 July 1984
Effect of Early Institutionalization and Foster Care on Long-term White Matter Development
Authors: Johanna Bick, Tong Zhu, Catherine Stamoulis, Nathan A. Fox, Charles Zeanah, Charles A. Nelson
Journal: JAMA Pediatrics (2015)

Severe neglect in early life is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in the white matter pathways that underlie emotional and cognitive development are unknown.To examine associations among neglect in early life, early intervention, and the microstructural integrity of white matter pathways in middle childhood.The Bucharest Early Intervention Project is a randomized clinical trial of high-quality foster care as an intervention for institutionally reared children in Bucharest, Romania, from 2000 through the present. During infancy, children were randomly selected to remain in an institution or to be placed in foster care. Those who remained in institutions experienced neglect, including social, emotional, linguistic, and cognitive impoverishment. Developmental trajectories of these children were compared with a group of sociodemographically matched children reared in biological families at baseline and several points throughout development. At approximately 8 years of age, 69 of the original 136 children underwent structural magnetic resonance imaging scans.Four estimates of white matter integrity (fractional anisotropy [FA] and mean [MD], radial [RD], and axial [AD] diffusivity) for 48 white matter tracts throughout the brain were obtained through diffusion tensor imaging.Significant associations emerged between neglect in early life and microstructural integrity of the body of the corpus callosum (FA, β = 0.01 [P = .01]; RD, β = -0.02 [P = .005]; MD, β = -0.01 [P = .02]) and tracts involved in limbic circuitry (fornix crus [AD, β = 0.02 (P = .046)] and cingulum [RD, β = -0.01 (P = .02); MD, β = -0.01 (P = .049)]), frontostriatal circuitry (anterior [AD, β = -0.01 (P = .02)] and superior [AD, β = -0.02 (P = .02); MD, β = -0.01 (P = .03)] corona radiata and external capsule [right FA, β = 0.01 (P = .03); left FA, β = 0.01 (P = .03); RD, β = -0.01 (P = .01); MD, β = -0.01 (P = .03)]), and sensory processing (medial lemniscus [AD, β = -0.02 (P = .045); MD, β = -0.01 (P = .04)] and retrolenticular internal capsule [FA, β = -0.01 (P = .002); RD, β = 0.01 (P = .003); MD, β = 0.01 (P = .04)]). Follow-up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care.Results suggest that removal from conditions of neglect in early life and entry into a high-quality family environment can support more normative trajectories of white matter growth. Our findings have implications for public health and policy efforts designed to promote normative brain development among vulnerable children.clinicaltrials.gov Identifier: NCT00747396.