tbuckley/cabot-search huggingface dataset:
Maternal Malignancies Detected With Noninvasive Prenatal Testing—Reply
Authors: Meredith Halks-Miller, Darya Chudova, Diana W. Bianchi
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
Redundant Mechanisms Regulating Brain Tyrosine and Tryptophan Hydroxylases
Authors: A J Mandell
Journal: The Annual Review of Pharmacology and Toxicology (1978)

rine, dopamine, and serotonin. In addition to presenting a view of some of today's issues, this paper emphasizes the Simultaneity and redundancy of the mechanisms being discussed. The brain must maintain both its sensitivity and inertia, and it appears to do so through a group of control mechanisms that are layered over each other along the dimension of time, with varying degrees of specificity and potency. The breadth attempted in this review looks toward the day when regulatory influ­ ences will no longer be discussed on an either/or basis, because investigators in different laboratories focus their attention on separate mechanisms, and the issues will be seen as requiring the simultaneous measurement of multiple parameters and data reduction through pattern analyses using multivariate . statistics. The areas to be covered in this review include regulation by (a) the kinetic interactions of reactants and products, (b) conformational alterations in enzyme, (c) supply of amino acid substrate, (d) supply of reduced pterin cofactor, (e) amount of enzyme protein, and (I) neurophysiologic al organization.
HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors
Authors: Karen T. Tashima, Laura M. Smeaton, Carl J. Fichtenbaum, Adriana Andrade, Joseph J. Eron, Rajesh T. Gandhi, Victoria A. Johnson, Karin L. Klingman, Justin Ritz, Sally Hodder, Jorge L. Santana, Timothy Wilkin, Richard H. Haubrich
Journal: Annals of Internal Medicine (2015)

Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials.To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents.Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394).Outpatient HIV clinics.Treatment-experienced patients with HIV infection and viral resistance.Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs.The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment.360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group.Unblinded study design, and the study may not be applicable to resource-poor settings.Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population.National Institute of Allergy and Infectious Diseases, Boehringer Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram Biosciences (LabCorp).
Immunotherapy-Induced Regulatory T Cells in Mice Sensitized to Peanut: Epicutaneous Vs Sublingual
Authors: Vincent Dioszeghy, Lucie Mondoulet, Véronique Dhelft, Mélanie Ligouis, Emilie Puteaux, Christophe Dupont, Pierre Henri Benhamou
Journal: Journal of Allergy and Clinical Immunology (2013)
Pharmacogenetics: Defective Enzymes in Relation to Reactions to Drugs
Authors: B N L Du
Journal: Annual Review of Medicine (1972)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer.
Authors: L De Andrés, J Brunet, A López-Pousa, J Burgués, M Vega, J M Tabernero, R Mesía, J J López
Journal: Journal of Clinical Oncology (1995)

PURPOSE A randomized trial was designed to compare cisplatin (CDDP) and fluorouracil (FU) versus carboplatin (CBDCA) and FU as neoadjuvant treatment in stage IV-M0 head and neck cancer to assess whether CBDCA-FU is better than CDDP-FU with regard to response and toxicity. PATIENTS AND METHODS Patients were randomized to receive CDDP 100 mg/m2 intravenously on day 1 and FU 5,000 mg/m2 over a 120-hour continuous infusion, or CBDCA 400 mg/m2 over a 24-hour continuous infusion on day 1 and FU with the same schedule. Both regimens were repeated every 21 days. The patients received three courses of chemotherapy, excluding those who failed to achieve a partial response (PR) after the second course. Complete responders were treated with radiotherapy. The remaining patients underwent surgery if the tumor was resectable. RESULTS Interim analysis was performed when 95 patients were included. The trial was stopped due to significantly better results in the control arm. Differences in response (P = .04) were favorable to CDDP-FU. Hematologic toxicity predominated in the CBDCA-FU arm (P &lt; .001). Mucositis and vomiting predominated in the CDDP-FU arm (P = .03, P &lt; .001, respectively). Favorable outcomes (complete response [CR] plus any grade of toxicity and PR plus grade 0 to 3 toxicity) predominated in the CDDP-FU arm (P = .02). Only the treatment assigned was associated with response (P = .02) and favorable outcomes (P = .009) in the logistic regression analysis. In the CDDP-FU arm, disease-free and overall survival were significantly better. Cox regression analysis showed that only treatment association with disease-free survival remains significant. CONCLUSION Our results indicate that CDDP-FU is more effective than CBDCA-FU as neoadjuvant treatment in stage IV-M0 head and neck cancer.
New health promotion for chemsex and γ-hydroxybutyrate (GHB)
Authors: Adam Winstock
Journal: BMJ (2015)

McCall and colleagues point out the growing problem of chemsex in the UK and the need for a coordinated policy and health response.1 Although there are common sexual behavioural risks associated with the use of any intoxicant that reduces inhibition, few would suggest that alcohol improves performance. This is not the case with γ-hydroxybutyrate (GHB), crystallised methamphetamine, and mephedrone, which can increase arousal, stamina, and pleasure.

These drugs also carry specific …
Complement Factor H-Related 5-Hybrid Proteins Anchor Properdin and Activate Complement at Self-Surfaces
Authors: Qian Chen, Melanie Manzke, Andrea Hartmann, Maike Büttner, Kerstin Amann, Diana Pauly, Michael Wiesener, Christine Skerka, Peter F. Zipfel
Journal: Journal of the American Society of Nephrology (2015)

C3 glomerulopathy (C3G) is a severe kidney disease for which no specific therapy exists. The causes of C3G are heterogeneous, and defective complement regulation is often linked to C3G pathogenesis. Copy number variations in the complement factor H-related ( CFHR ) gene cluster on chromosome 1q32 and CFHR5 mutant proteins associate with this disease. Here, we identified CFHR5 as a pattern recognition protein that binds to damaged human endothelial cell surfaces and to properdin, the human complement activator. We found the two N-terminal short consensus repeat domains of CFHR5 contact properdin and mediate dimer formation. These properdin-binding segments are duplicated in two mutant CFHR5 proteins, CFHR2-CFHR5 Hyb from German patients with C3G and CFHR5 Dup from Cypriot patients with C3G. Each of these mutated proteins assembled into large multimeric complexes and, compared to CFHR5, bound damaged human cell surfaces and properdin with greater intensity and exacerbated local complement activation. This enhanced surface binding and properdin recruitment was further evidenced in the mesangia of a transplanted and explanted kidney from a German patient with a CFHR2-CFHR5 Hyb protein. Enhanced properdin staining correlated with local complement activation with C3b and C5b-9 deposition on the mesangial cell surface in vitro . This gain of function in complement activation for two disease-associated CFHR5 mutants describes a new disease mechanism of C3G, which is relevant for defining appropriate treatment options for this disorder.
Abstract 300: increasing radiation dose enhances immunotherapy efficacy and together prolongs tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma
Authors: Henry M. Smilowitz, Peggy Micca, Daniel Sasso, Qian Wu, Nathanial Dyment, Lynn Kuo
Journal: Cancer Research (2015)

Abstract Previously we developed a clinically relevant therapy model for advanced intracerebral B16 melanomas in syngeneic mice combining radiation and immunotherapies. Here seven days after B16F10Luc2 melanoma cells were implanted intracerebrally (D7), syngeneic mice with bioluminescent tumors that had formed (1E105 to 7E106 photons/minute (&amp;gt;1E106, large (L); &amp;lt;1E106, small (S)) were segregated into L/S-balanced subgroups. Then, mice received either radiation therapy alone (RT) or radiation therapy plus immunotherapy (RT plus IT). Radiation dose was varied (15, 18.75 or 22.5 Gray (Gy), given on D8), while immunotherapy was provided similarly to all mice. The data support the hypothesis that increasing radiation dose increases the efficacy of immunotherapy in a subgroup of mice. The tumors that were greatly delayed in beginning their progressive growth were bioluminescent in vivo–some for many months, indicating prolonged tumor “dormancy,” in some cases presaging long-term cures. Mice bearing such tumors far more likely had received radiation plus immunotherapy than radiation alone. Radiotherapy is a very important adjunct to immunotherapy; the greater the tumor debulking by radiation therapy, the greater should be the benefit to tumor immunotherapy. Citation Format: Henry M. Smilowitz, Peggy Micca, Daniel Sasso, Qian Wu, Nathanial Dyment, Lynn Kuo. increasing radiation dose enhances immunotherapy efficacy and together prolongs tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 300. doi:10.1158/1538-7445.AM2015-300
Abbreviated treatment for elderly, infirm, or noncompliant patients with limited-stage small-cell lung cancer.
Authors: N Murray, C Grafton, A Shah, K Gelmon, E Kostashuk, E Brown, C Coppin, A Coldman, R Page
Journal: Journal of Clinical Oncology (1998)

To evaluate the efficacy of an abbreviated treatment plan consisting of two cycles of chemotherapy plus thoracic irradiation in a population of limited-stage small-cell lung cancer (LSCLC) patients who were elderly, infirm, or noncompliant with standard-duration therapy.Fifty-five LSCLC patients (median age, 73) were treated with one cycle of cyclophosphamide, doxorubicin, and vincristine (CAV) followed 3 weeks later by one cycle of etoposide and cisplatin (EP). Both regimens were administered at conventional full dose. Thoracic irradiation (20 to 30 Gy) was delivered concurrently with EP.Complete response occurred in 28 patients (51%) and partial response in 21 (38%). The median survival time was 54 weeks; the 2-year survival rate was 28% and the actual 5-year survival rate was 18%. Three patients died of toxicity.Elderly, infirm, or noncompliant LSCLC patients who are unable to receive standard-duration chemotherapy may have useful palliation and potential for long-term survival with abbreviated chemotherapy (two cycles) and thoracic irradiation.
Insulin–InsR signaling drives multipotent progenitor differentiation toward lymphoid lineages
Authors: Pengyan Xia, Shuo Wang, Ying Du, Guanling Huang, Takashi Satoh, Shizuo Akira, Zusen Fan
Journal: The Journal of Experimental Medicine (2015)

The lineage commitment of HSCs generates balanced myeloid and lymphoid populations in hematopoiesis. However, the underlying mechanisms that control this process remain largely unknown. Here, we show that insulin–insulin receptor (InsR) signaling is required for lineage commitment of multipotent progenitors (MPPs). Deletion of Insr in murine bone marrow causes skewed differentiation of MPPs to myeloid cells. mTOR acts as a downstream effector that modulates MPP differentiation. mTOR activates Stat3 by phosphorylation at serine 727 under insulin stimulation, which binds to the promoter of Ikaros, leading to its transcription priming. Our findings reveal that the insulin–InsR signaling drives MPP differentiation into lymphoid lineages in early lymphopoiesis, which is essential for maintaining a balanced immune system for an individual organism.
Excitatory Amino Acid Transmitters
Authors: J C Watkins, R H Evans
Journal: The Annual Review of Pharmacology and Toxicology (1981)

Excitatory Amino Acid Transmitters, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/pharmtox/21/1/annurev.pa.21.040181.001121-1.gif
Sex Differences in Airway Remodeling in a Mouse Model of Chronic Obstructive Pulmonary Disease
Authors: Anthony Tam, Andrew Churg, Joanne L. Wright, Steven Zhou, Miranda Kirby, Harvey O. Coxson, Stephen Lam, S. F. Paul Man, Don D. Sin
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

After adjustment for the amount of smoking, women have a 50% increased risk of chronic obstructive pulmonary disease (COPD) compared with men. The anatomic basis and/or mechanism(s) of these sex-related differences in COPD are unknown.To characterize the impact of female sex hormones on chronic cigarette smoke-induced airway remodeling and emphysema in a mouse model of COPD.Airway remodeling and emphysema were determined morphometrically in male, female, and ovariectomized mice exposed to 6 months of cigarette smoke. Antioxidant- and transforming growth factor (TGF)-β-related genes were profiled in airway tissues. The selective estrogen receptor modulator tamoxifen was also administered during smoke exposure in a short-term model. Airway wall thickness of male and female human smokers at risk of or with mild COPD was measured using optical coherence tomography.Small airway wall remodeling was increased in female but not male or ovariectomized mice and was associated with increased distal airway resistance, down-regulation of antioxidant genes, increased oxidative stress, and activation of TGF-β1. These effects were prevented by ovariectomy. Use of tamoxifen as a therapeutic intervention mitigated smoke-induced increase in oxidative stress in female mice. Compared with male human smokers, female human smokers had significantly thicker airway walls.The excess risk of small airway disease in female mice after chronic smoke exposure was associated with increased oxidative stress and TGF-β1 signaling and also was related to the effects of female sex hormones. Estrogen receptor antagonism might be of value in reducing oxidative stress in female smokers.
Small pharmacies are more likely to dispense antibiotics without a medical prescription than large pharmacies in Catalonia, Spain
Authors: C Llor, D L Monnet, J M Cots
Journal: Eurosurveillance (2010)

The aim of this study was to explore the relationship between pharmacy size and the likelihood of obtaining antibiotics without medical prescription at a pharmacy. In 2008 in Catalonia, two actors presented three different cases in a randomised sample of pharmacies and asked pharmacists for an antibiotic. Pharmacies were considered as small when having limited space with only one counter and a maximum of two professionals selling medicines, as medium sized with three or four attending professionals, and as large with a large selling space and more than four attending professionals. Of the 197 pharmacies visited, 88 (44.7%) were considered as small while only 25 (12.7%) were large. Antibiotics were obtained without a medical prescription in 89 (45.2%) pharmacies, mainly in small pharmacies (63.6%), followed by medium-sized pharmacies (35.7%) and large pharmacies (12%) (p<0.001). Large pharmacies, that probably have a greater income, more closely followed the prevailing legislation of not selling antibiotics to patients without a medical prescription. This observation should now be confirmed in other countries where over-the-counter sales of antibiotics are prevalent and should be taken into account by programmes aiming at achieving a more prudent use of antibiotics.
Post-Transplant Cyclophosphamide Haplo-HSCT Revised: Peripheral Blood Stem Cell Graft and Sirolimus To Enhance Immune Reconstitution and Graft Versus Leukemia Effect In Patients With Active Leukemia
Authors: Nicoletta Cieri, Raffaella Greco, Mara Morelli, Fabio Giglio, Andrea Assanelli, Alessandra Forcina, Maria Teresa Lupo Stanghellini, Massimo Bernardi, Consuelo Corti, Chiara Bonini, Fabio Ciceri, Jacopo Peccatori
Journal: Blood (2013)
Part 2: Evidence Evaluation and Management of Conflicts of Interest
Authors: Peter T. Morley, Eddy Lang, Richard Aickin, John E. Billi, Brian Eigel, Jose Maria E. Ferrer, Judith C. Finn, Lana M. Gent, Russell E. Griffin, Mary Fran Hazinski, Ian K. Maconochie, William H. Montgomery, Laurie J. Morrison, Vinay M. Nadkarni, Nikolaos I. Nikolaou, Jerry P. Nolan, Gavin D. Perkins, Michael R. Sayre, Andrew H. Travers, Jonathan Wyllie, David A. Zideman
Journal: Circulation (2015)

The process for evaluating the resuscitation science has evolved considerably over the past 2 decades. The current process, which incorporates the use of the GRADE methodology, culminated in the 2015 CoSTR publication, which in turn will inform the international resuscitation councils’ guideline development processes. Over the next few years, the process will continue to evolve as ILCOR moves toward a more continuous evaluation of the resuscitation science.
Biliary sclerosis in patients receiving hepatic arterial infusions of floxuridine.
Authors: D Hohn, J Melnick, R Stagg, D Altman, M Friedman, R Ignoffo, L Ferrell, B Lewis
Journal: Journal of Clinical Oncology (1985)

High response rates have been reported with hepatic intra-arterial infusions of floxuridine in patients having colorectal carcinoma metastatic to the liver. The major toxicity of this therapy has been described as "chemical hepatitis." In a randomized trial of intravenous v intra-arterial floxuridine, we observed that all 35 patients receiving intra-arterial therapy developed significant increases in alkaline phosphatase and, in some cases, serum glutamic oxaloacetic transminase and/or bilirubin. Seven patients receiving intra-arterial therapy were studied with cholangiography which, in all cases, demonstrated sclerosis of the intrahepatic and/or extrahepatic bile ducts. In addition, liver biopsies showed cholestasis and pericholangitis with minimal hepatocyte damage. These findings suggest that "biliary sclerosis" rather than "chemical hepatitis" is the predominant toxicity associated with hepatic intra-arterial infusions of floxuridine.
Adjuvant Chemotherapy Use and Health Care Costs After Introduction of Genomic Testing in Breast Cancer
Authors: Andrew J. Epstein, Yu-Ning Wong, Nandita Mitra, Anil Vachani, Sakhena Hin, Lin Yang, Aaron Smith-McLallen, Katrina Armstrong, Peter W. Groeneveld
Journal: Journal of Clinical Oncology (2015)

We assessed the associations between the 21-gene recurrence score assay (RS) receipt, subsequent chemotherapy use, and medical expenditures among patients with early-stage breast cancer.Data from the Pennsylvania Cancer Registry were used to assemble a retrospective cohort of women with early-stage breast cancer from 2007 to 2010 who underwent initial surgical treatment. These data were merged with administrative claims from the 12-month periods before and after diagnosis to identify comorbidities, treatments, and expenditures (n = 7,287). Propensity score-weighted regression models were estimated to identify the effects of RS receipt on chemotherapy use and medical spending in the year after diagnosis.The associations between RS receipt and outcomes varied markedly by patient age. RS use was associated with lower chemotherapy use among women younger than 55 (19.2% lower; 95% CI, 10.6 to 27.9). RS use was associated with higher chemotherapy use among women 75 to 84 years old (5.7% higher; 95% CI, 0.4 to 11.0). RS receipt was associated with lower adjusted 1-year medical spending among women younger than 55 ($15,333 lower; 95% CI, $2,841 to $27,824) and with higher spending among women who were 75 to 84 years old ($3,489 higher; 95% CI, $857 to $6,122).RS receipt was associated with reduced use of adjuvant chemotherapy and lower health care spending among women with breast cancer who were younger than 55. Conversely, among women 75 and older, RS testing was associated with a modest increase in chemotherapy use and slightly higher spending. From a population perspective, the impact of RS testing on breast cancer treatment and health care costs is much greater in younger women.