tbuckley/cabot-search huggingface dataset:
Pharmacovigilance of drug allergy and hypersensitivity using the ENDA–DAHD database and the GA<sup>2</sup>LEN platform. The Galenda project
Authors: P.‐J. Bousquet, P. Demoly, A. Romano, W. Aberer, A. Bircher, M. Blanca, K. Brockow, W. Pichler, M. J. Torres, I. Terreehorst, B. Arnoux, M. Atanaskovic‐Markovic, A. Barbaud, A. Bijl, P. Bonadonna, P. G. Burney, S. Caimmi, G. W. Canonica, J. Cernadas, B. Dahlen, J.‐P. Daures, J. Fernandez, E. Gomes, J.‐L. Gueant, M. L. Kowalski, V. Kvedariene, P.‐M. Mertes, P. Martins, E. Nizankowska‐Mogilnicka, N. Papadopoulos, C. Ponvert, M. Pirmohamed, J. Ring, M. Salapatas, M. L. Sanz, A. Szczeklik, E. Van Ganse, A. L. De Weck, T. Zuberbier, H. F. Merk, B. Sachs, A. Sidoroff
Journal: Allergy (2009)

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.
Gadd45β is an inducible coactivator of transcription that facilitates rapid liver growth in mice
Authors: Jianmin Tian, Haiyan Huang, Barbara Hoffman, Dan A. Liebermann, Giovanna M. Ledda-Columbano, Amedeo Columbano, Joseph Locker
Journal: Journal of Clinical Investigation (2011)

The growth arrest and DNA damage-inducible 45 (Gadd45) proteins act in many cellular processes. In the liver, Gadd45b (encoding Gadd45β) is the gene most strongly induced early during both compensatory regeneration and drug-induced hyperplasia. The latter response is associated with the dramatic and rapid hepatocyte growth that follows administration of the xenobiotic TCPOBOP (1,4-bis[2-(3,5)-dichoropyridyloxy] benzene), a ligand of the nuclear receptor constitutive androstane receptor (CAR). Here, we have shown that Gadd45b-/- mice have intact proliferative responses following administration of a single dose of TCPOBOP, but marked growth delays. Moreover, early transcriptional stimulation of CAR target genes was weaker in Gadd45b-/- mice than in wild-type animals, and more genes were downregulated. Gadd45β was then found to have a direct role in transcription by physically binding to CAR, and TCPOBOP treatment caused both proteins to localize to a regulatory element for the CAR target gene cytochrome P450 2b10 (Cyp2b10). Further analysis defined separate Gadd45β domains that mediated binding to CAR and transcriptional activation. Although baseline hepatic expression of Gadd45b was broadly comparable to that of other coactivators, its 140-fold stimulation by TCPOBOP was striking and unique. The induction of Gadd45β is therefore a response that facilitates increased transcription, allowing rapid expansion of liver mass for protection against xenobiotic insults.
MORPHOLOGIC CHANGES ACCOMPANYING SENESCENCE OF CULTURED HUMAN DIPLOID CELLS
Authors: E. Robbins, E. M. Levine, H. Eagle
Journal: The Journal of Experimental Medicine (1970)

The lysosomes of serially propagated human fibroblasts gradually transform to residual bodies which increase in number and size, and show progressive degenerative changes. There is an accompanying, and less regular, decrease in the number of cytoplasmic polyribosomes and an increased number of glycogen particles. The onset of these morphologic alterations occurs shortly after culture initiation and precedes any marked decrease in the rate of cellular growth; however, in their extreme form these changes may be related to the ultimate cessation of cellular multiplication ("senescence"). The lysosomal changes were seen only in those cell strains which eventually showed senescence, and were absent or minimal either in cell lines which can be propagated indefinitely ("spontaneous" and viral transformants, cancer cells), or in skin sections from aging subjects.
Diabetes Preventive Services and Policy Implications in the U.S.
Authors: Xiaoxing Z. He
Journal: Diabetes Care (2010)

OBJECTIVE To investigate whether the patient or physician practice characteristics predict the use of diabetes preventive care services. RESEARCH DESIGN AND METHODS This was a cross-sectional study of a nationally representative sample of 27,169 adult ambulatory care visits, using the 2007 National Ambulatory Medical Care Survey data. The outcome variable is whether any preventive care services, defined as diagnostic tests (glucose, urinalysis, A1C, and blood pressure) or patient education (diet/nutrition, exercise, and stress management), were ordered/provided. Multivariate analysis was performed to identify independent predictors of diabetes preventive care services, controlling for patient and physician practice characteristics. All analyses were adjusted for the complex survey design and analytic weights. RESULTS Compared with people without diabetes, diabetic patients were older (63 vs. 53 years; P &amp;lt; 0.01) and were more likely to be nonwhite and covered by Medicare insurance. In multivariate analyses, younger patients and the availability of primary care physicians, electronic medical records, and on-site laboratory tests were associated with more effective preventive care services (P &amp;lt; 0.05). If physician compensation relied on productivity, preventive care services were less likely (odds ratio 0.4 [95% CI 0.27–0.82 for men and 0.26–0.81 for women]). Although the patterns of patient education and diagnostic testing were similar, the provision of patient education was less likely than that of diagnostic testing. CONCLUSIONS Primary care physicians and practice features seem to steer diabetes preventive services. Given the time constraints of physicians, strategies to strengthen structural capabilities of primary care practices and enhance partnerships with public health systems on diabetic patient education are recommended.
Study Says Stay Calm and Halve Risk of Stroke
Authors: Pat Phillips
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
Tenofovir Effect on the Kidneys of HIV-Infected Patients
Authors: Jérôme Tourret, Gilbert Deray, Corinne Isnard-Bagnis
Journal: Journal of the American Society of Nephrology (2013)

Tenofovir disoproxil fumarate (TDF), the first nucleotidic inhibitor of HIV reverse transcription, became available in 2001. It has been extensively used worldwide and is now the most prescribed antiretroviral (ARV) drug. Its high antiviral activity and favorable metabolic profile are responsible for its success. Furthermore, TDF has been associated with other ARVs to form new combined antiretroviral treatments in only one tablet once-a-day, which increases treatment adherence. Fears of potential nephrotoxicity that tenofovir would have in common with two other drugs from the same family (adefovir, used to treat hepatitis B, and cidofovir, used to treat cytomegalovirus infections) were alleviated by the early clinical trials. Yet, in 2001, the first case of TDF-induced acute nephrotoxicity was published. Numerous cases have been published since then, and it is now established that TDF presents a tubular toxicity risk. Some facilitating factors have been identified, such as co-prescription of didanosine or boosted protease inhibitor, preexisting CKD, low body weight, and associated diabetes mellitus. Conversely, whether TDF is nephrotoxic in the long term is a highly debated question. Some studies suggest a decreased GFR when TDF is prescribed for a long period, while others indicate that TDF is safe for the kidneys even after many years of use. Here we review the differences in patient characteristics, study designs, and measured outcomes that can possibly explain these conflicting findings. We conclude with rational recommendation for appropriate TDF prescription.
Diagnostic Controversies in Adult Attention Deficit Hyperactivity Disorder
Authors: James J McGough, Russell A Barkley
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: While it is increasingly recognized that attention deficit hyperactivity disorder (ADHD) persists into adulthood, there is no consensus on diagnostic criteria for adult ADHD. In this article the authors describe and contrast competing approaches for diagnosis of adult ADHD used in clinical and research practice. METHOD: The authors review the Wender Utah criteria, DSM criteria, and laboratory assessment strategies for adult ADHD. Advantages and disadvantages of each approach are described, and recommendations are made as a basis for clinical assessment and future research. RESULTS: Both the Wender Utah criteria and DSM-based approaches identify significantly impaired ADHD adults with neurocognitive, biological, and treatment response patterns similar to pediatric ADHD patients. The Wender Utah criteria established the need for retrospective childhood diagnosis and recognize developmental differences in adult symptom expression. The Wender Utah criteria fail to identify patients with predominately inattentive symptoms, exclude some patients with significant comorbid psychopathology, and diverge significantly from the DSM conception of ADHD. The DSM criteria have never been validated in adults, do not include developmentally appropriate symptoms and thresholds for adults, and fail to identify some significantly impaired adults who are likely to benefit from treatment. There are insufficient scientific data to justify use of laboratory assessment measures, including neuropsychological tests and brain imaging, in diagnosing adult ADHD. CONCLUSIONS: Adult ADHD remains a clinical diagnosis. Clinicians should be flexible in application of the current ADHD criteria to adults. Additional research is required to validate adult diagnostic criteria.
Therapeutic PD-1 Pathway Blockade Augments with Other Modalities of Immunotherapy T-Cell Function to Prevent Immune Decline in Ovarian Cancer
Authors: Jaikumar Duraiswamy, Gordon J. Freeman, George Coukos
Journal: Cancer Research (2013)

Abstract The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment, using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8). Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor-associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor cells (MDSC). When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony—stimulating factor or FLT3 ligand) and costimulation by agonistic α-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. This therapeutic effect was associated with increased proliferation and function of tumor antigen-specific effector CD8+ T cells, inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of effector T-cell signaling molecules, and generation of T memory precursor cells. Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by reprogramming suppressive and stimulatory signals that yielded more powerful cancer control. Cancer Res; 73(23); 6900–12. ©2013 AACR.
Tuberculosis and mediastinoscopy.
Authors: E W Cameron
Journal: Thorax (1978)

Biopsy of lymph nodes at mediastinoscopy has been the method of diagnosis of tuberculosis in 14 patients; Mycobacterium tuberculosis was cultured from the nodes in nine cases, and in five there was histological evidence of the disease but cultural confirmation was lacking. All patients had radiographic abnormality of the superior mediastinum, and a frequent finding at mediastinoscopy was mediastinal fibrosis involving the fascia and lymph nodes. No cause other than tuberculosis could be demonstrated to account for the mediastinal fibrosis, and the patients made clinical recoveries in response to standard courses of antituberculosis chemotherapy. The development of superior vena caval compression was not observed.
Neutrophil Infiltration of Culprit Lesions in Acute Coronary Syndromes
Authors: Takahiko Naruko, Makiko Ueda, Kazuo Haze, Allard C. van der Wal, Chris M. van der Loos, Akira Itoh, Ryushi Komatsu, Yoshihiro Ikura, Masayuki Ogami, Yoshihisa Shimada, Shoichi Ehara, Minoru Yoshiyama, Kazuhide Takeuchi, Junichi Yoshikawa, Anton E. Becker
Journal: Circulation (2002)

Neutrophils in unstable atherosclerotic lesions have not received much consideration, despite accumulating evidence suggesting a link between systemic inflammation and acute coronary syndromes.Coronary artery segments were obtained at autopsy from 13 patients with acute myocardial infarction (AMI); 8 had a ruptured and 5 an eroded plaque. Patients (n=45) who had died of noncardiovascular diseases served as reference. Atherectomy specimens were obtained from 35 patients with stable angina pectoris (SAP) and from 32 patients with unstable angina pectoris (UAP). Antibodies against CD66b, elastase, myeloperoxidase, and CD11b identified neutrophils; CD10 identified neutral endopeptidase (NEP). CD66b-positive and NEP-positive neutrophils were counted and expressed as a number per square millimeter of tissue. All specimens with plaque rupture or erosion showed distinct neutrophil infiltration; the number did not differ between ruptured and eroded plaques. However, the number of NEP-positive neutrophils was significantly higher (P<0.0001) in ruptured plaques than in eroded plaques. UAP patients showed neutrophils in 14 of 32 culprit lesions; in SAP only 2 of 35 lesions contained neutrophils. The number of neutrophils and NEP-positive cells in patients with UAP was significantly higher (neutrophils, P<0.0005; NEP-positive cells, P<0.005) than in patients with SAP.The observations suggest that neutrophil infiltration is actively associated with acute coronary events. The high number of NEP-positive neutrophils in ruptured plaques, compared with eroded plaques, may reflect differences in the underlying pathophysiological mechanisms.
Abstract 1571: The tumor suppressor Liver Kinase B1 inhibits triple-negative breast cancer cell metastasis via regulation of AP-1 signaling
Authors: Lyndsay V. Rhodes, Chandra R. Tate, Hope E. Burks, Van T. Hoang, Diari Gilliam, Elizabeth C. Martin, Steven Elliott, David F. Miller, Aaron Buechlein, Douglas Rusch, Haixu Tang, Kenneth P. Nephew, Matthew E. Burow, Bridgette M. Collins-Burow
Journal: Cancer Research (2014)

Abstract The basal sub-type, which shares features with triple-negative breast cancer (TNBC), is among the most lethal breast cancer subtype, characterized by a highly aggressive and metastatic phenotype. Although pathways that may represent targets for novel therapeutic intervention for basal like breast cancer (BLBC) have begun to be elucidated, the ability to define and selectively target the invasive and metastatic phenotype of basal-type/TNBC remains a major challenge facing the breast cancer field. Liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is a known tumor suppressor in many cancers including breast. Low LKB1expression has been observed in breast cancer patients and we report a significant association between loss of LKB1 expression and poor prognosis specifically in the basal sub-type of breast cancer. Induction of LKB1 expression in BLBC cell lines inhibited invasiveness in vitro as well as lung and brain metastatic burden in an orthotopic xenograft tumor model. Further analysis of BLBC cell lines overexpressing LKB1 by next generation sequencing (RNA-seq) revealed striking regulation of metastasis-associated pathways, including cell adhesion, extra cellular matrix remodeling, and epithelial-to-mesenchymal transition (EMT). We further demonstrated marked inhibition of matrix metalloproteinase 1 (MMP-1) expression and activity via regulation AP-1 family member cJun. Additionally, LKB1 overexpression inhibited EMT-associated genes (CDH2, Vimentin, Twist) and induced the epithelial cell marker CDH1, indicating a reversal of the EMT phenotype in a triple-negative breast cancer cell line MDA-MB-231. We have demonstrated a role for LKB1 expression in the regulation of cell invasion and metastasis in addition to tumorigenesis. Taken together these data support future development of therapeutic agents to induce the LKB1 signaling pathway in BLCB/triple-negative breast cancer. Citation Format: Lyndsay V. Rhodes, Chandra R. Tate, Hope E. Burks, Van T. Hoang, Diari Gilliam, Elizabeth C. Martin, Steven Elliott, David FB Miller, Aaron Buechlein, Douglas Rusch, Haixu Tang, Kenneth P. Nephew, Matthew E. Burow, Bridgette M. Collins-Burow. The tumor suppressor Liver Kinase B1 inhibits triple-negative breast cancer cell metastasis via regulation of AP-1 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 1571. doi:10.1158/1538-7445.AM2014-1571
Human Hepatocellular Carcinoma Tumor–derived Endothelial Cells Manifest Increased Angiogenesis Capability and Drug Resistance Compared with Normal Endothelial Cells
Authors: Yu-Quan Xiong, Hui-Chuan Sun, Wei Zhang, Xiao-Dong Zhu, Peng-Yuan Zhuang, Ju-Bo Zhang, Lu Wang, Wei-zhong Wu, Lun-Xiu Qin, Zhao-You Tang
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Increasing evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype compared with endothelial cells (NEC) from adjacent normal tissue and may be able to acquire resistance to drugs. The aim of this study was to investigate the angiogenesis activity and response to drug treatment of TECs and NECs derived from human hepatocellular carcinoma (HCC). Experimental Design: TECs or NECs were isolated from HCC or adjacent normal liver tissue using anti-CD105 antibody coupled to magnetic beads. The phenotypic and functional properties of endothelial cells were characterized by testing the expression of CD105, CD31, CD144, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and von Willebrand factor, and the ability of DiI-Ac-LDL-uptake and tube formations. CD105+ TECs were compared with CD105+ NECs and human umbilical vein endothelial cells (HUVEC) by examining their ability to proliferate, motility, ability to adhere to tumor cells, response to tumor conditioned medium, and reactions to the chemotherapy drugs Adriamycin and 5-fluorouracil and the antiangiogenic drug sorafenib. Results: Compared with CD105+ NECs and HUVECs, CD105+ TECs showed increased apoptosis resistance and motility and proangiogenic properties. Meanwhile, CD105+ TECs had a greater ability to adhere to tumor cells and survive in the tumor environment. Moreover, CD105+ TECs acquired more resistance to Adriamycin, 5-fluorouracil, and sorafenib than CD105+ NECs and HUVECs. Conclusions: TECs possessed enhanced angiogenic activity and resistance to chemotherapeutic drugs and an angiogenesis inhibitor, and may provide a better tool for studying tumor angiogenesis and antiangiogenesis drugs in HCC.
Hyperhomocyst(e)inemia as a Risk Factor for Occlusive Vascular Disease
Authors: S S Kang, P W Wong, M R Malinow
Journal: Annual Review of Nutrition (1992)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Peroxynitrite-induced myocardial injury is mediated through matrix metalloproteinase-2
Authors: W Wang
Journal: Cardiovascular Research (2002)

Objectives: Peroxynitrite (ONOO−) mediates in part both ischemia–reperfusion and pro-inflammatory cytokine-induced injury to the heart. As oxidants like ONOO− are known to activate matrix metalloproteinases (MMPs), we examined whether they play a role in the detrimental action of ONOO− in isolated perfused rat hearts. Methods: Hearts were isolated from Sprague–Dawley rats and perfused retrogradely with Krebs–Henseleit buffer under constant flow. Peroxynitrite (30 and 80 μM) was infused into the hearts for 15 min. The release of MMPs into the coronary effluent and level of MMPs in the myocardium were measured by gelatin zymography. Results: The main gelatinolytic activity in control effluent was 72-kDa corresponding to pro-MMP-2. Infusion of ONOO− (80 μM) for 15 min caused a vasodilatation which peaked at 5 min and then converted into vasoconstriction by 15 min. It also caused a rapid increase in the release of 72-kDa activity within 10 min and a progressive decline in cardiac mechanical function. In contrast, decomposed ONOO− caused no change in vascular tone, the release of 72-kDa activity or mechanical function. The MMPs inhibitor PD-166793 prevented the ONOO−-induced loss in myocardial mechanical function. Detoxification of ONOO− with glutathione prevented both the enhancement in coronary effluent 72-kDa activity and the decline in mechanical function. Conclusions: Acute cardiac toxicity induced by ONOO− is mediated by MMP-2.