tbuckley/cabot-search huggingface dataset:
High-dose continuous infusion folinic acid and bolus 5-fluorouracil in patients with advanced colorectal cancer: a phase II study.
Authors: M Bertrand, J H Doroshow, P Multhauf, D W Blayney, B I Carr, G Cecchi, D Goldberg, L Leong, K Margolin, G Metter
Journal: Journal of Clinical Oncology (1986)

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.
Alterations in T- and B-Cells in Human Disease States
Authors: R C Williams, R P Messner
Journal: Annual Review of Medicine (1975)

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
Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage
Authors: Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Osamu Hashizume, Satoru Nagatoishi, Akihiro Matsuo, Takeya Sato, Tai Kudo, Tetsuro Matsuhashi, Kazutaka Murayama, Yuki Ohba, Shun Watanabe, Shin-ichiro Kanno, Daichi Minaki, Daisuke Saigusa, Hiroko Shinbo, Nobuyoshi Mori, Akinori Yuri, Miyuki Yokoro, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yoichi Takeuchi, Koichi Kikuchi, Takafumi Toyohara, Chitose Suzuki, Takaharu Ichimura, Jun-ichi Anzai, Masahiro Kohzuki, Nariyasu Mano, Shigeo Kure, Teruyuki Yanagisawa, Yoshihisa Tomioka, Masaaki Toyomizu, Kohei Tsumoto, Kazuto Nakada, Joseph V. Bonventre, Sadayoshi Ito, Hitoshi Osaka, Ken-ichi Hayashi, Takaaki Abe
Journal: Journal of the American Society of Nephrology (2015)

Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid–resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin–induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I–IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.
The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis
Authors: Jinkuk Choi, Jie Gao, Jaekwang Kim, Cynthia Hong, Jungsu Kim, Peter Tontonoz
Journal: Science Translational Medicine (2015)

Inhibiting the E3 ubiquitin ligase Idol in a mouse model of Alzheimer’s-like pathology ameliorates disease severity by promoting clearance of Aβ peptides by microglia.
The Value of Psychiatric Diagnoses
Authors: Stephan Heckers
Journal: JAMA Psychiatry (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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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 Psychiatry journal
All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health
Authors: Mark Lawler, Lillian L. Siu, Heidi L. Rehm, Stephen J. Chanock, Gil Alterovitz, John Burn, Fabien Calvo, Denis Lacombe, Bin Tean Teh, Kathryn N. North, Charles L. Sawyers
Journal: Cancer Discovery (2015)

Abstract Summary: The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages “team science” and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients. Cancer Discov; 5(11); 1133–6. ©2015 AACR.
Unplanned pregnancy in an epileptic. (Letter to the editor)
Authors: Kenyon Ie
Journal: BMJ (1972)

A woman graduate aged 28 years who for several years had been taking phenytoin 100 mg twice daily sulthiamine (Ospolot) 50 mg daily and Folex (ferrous gluconate and folic acid) 3 tablets a week for epilepsy had also taken an oral  contraceptive containing .05 mg ethinyl estradiol and 3 mg norethisterone acetate regularly for 4 months when she had amenorrhea.  She continued all her therapy for a further 2 months during which amenorrhea persisted.  She insists that she neither missed nor delayed taking a pill.  At this stage (3 months amenorrhea) she had  a pregnancy test which was positive so she discontinued the oral contraceptive.  Her last menstrual period finished on March 3 1971 and she bore a normal female child (5 1/4 lb) on December 15.  In recent years we have come to regard pregnancy as virtually impossible for a woman taking oral contraception correctly and the occasional amenorrhea experienced by many subjects as of no consequence.  Earlier however some concern was felt about the efficacy of oral contraceptives in a subject who was concurrently taking regular doses of certain other drugs (including those drugs used in treatment of epilepsy) on account of a laboratory  investigation which had shown in mice that such drugs could stimulate enzymes which promote metabolism of the contraceptive.  The Family Planning Association Clinic Handbook states that there is no evidence that this investigation has any relevance to a woman taking ovarian steroids at oral contraceptive dosage.  The case cited however suggests that epilepsy-therapy drugs may reduce the effectiveness of oral contraceptives as indicated by the experiments with mice.(FULL TEXT)
Old dog, new tricks: extracellular domain arginine methylation regulates EGFR function
Authors: David M. Epstein, Elizabeth Buck
Journal: Journal of Clinical Investigation (2015)

Conventional wisdom holds that methylation of RTKs should be restricted to intracellular sites. Alterations--such as deletion, mutation, and proteolytic cleavage events--to the extracellular ligand binding and dimer interface domains of the EGFR can induce EGFR dimer formation, leading to aberrant receptor activation and oncogenic activity. Recently, the extracellular domain of EGFR was also shown to be methylated, suggesting that posttranslational protein methylation events directed to the extracellular dimer interface provide another mechanism to regulate the EGFR activation state by modulating receptor dimerization. Critically, these methylation events abrogate response to conformation-specific therapeutic antibodies such as cetuximab. In this issue of the JCI, Liao et al. investigate the role of protein arginine methyltransferase I (PRMT1) in regulating EGFR function in colorectal cancer. The authors provide evidence that methylation of R198 and R200 within the dimer interface enhances growth factor ligand binding and cetuximab resistance through induction and stabilization of the active EGFR dimer conformation. Delineation of these and other subtleties involved in oncogenic RTK activation and their response to targeted therapies should facilitate the development of improved antibody-based treatments.
Treatment with clozapine
Authors: N. Fisher, B. Baigent
Journal: BMJ (1996)

exploring the sexual behaviour of patients where this may be clinically appropriate or an opportunity for preventive intervention exists; and two way communication between general practitioners and consultants in genitourinary medicine.3Coincident infection with HIV and other sexually transmitted infections, particularly those that cause genital ulceration, has been cited as a major cause of increased transmissibil- ity of HIV.If only out of self interest, the insurance indus- try should consider the long term consequences of underwriting procedures on the important sexual health promotion activities that are possi- ble in general practice.4Now that we have better epidemiological evidence about the spread of HIV, the Association of British Insurers is in a position to re-evaluate its dogged adherence to pre-existing practice.In 1993-4 the Kensington, Chelsea and Westminster health district had 1186 HIV positive residents who consulted HIV services.Their general practitioners knew of the diagnosis in only 761 of these patients.5If the British insurance industry still believes that it needs protection from HIV then it should recog- nise that the use of general practitioners at the underwriting stage is as helpful as a condom with a large hole in it.
An unusual cause of GI bleeding
Authors: Tzu-Haw Chen, Yi-Ju Chen, Chi-Ming Tai
Journal: Gut (2015)

A 62-year-old woman with a history of hypertension and diabetes mellitus presented with 3 days intermittent passage of melena. Physical examination was unremarkable. The pertinent laboratory findings were haemoglobin, 10.3 g/dL (normal range, 12.0–16.0 g/dL); platelet count, 136×103/μL (normal range, 150–400×103/μL); prothrombin time, 11.9 s (control, 10.6 s; international normalised ratio, 0.91); and activated partial thrombin time, 28.1 s (control, 31.3 s). Esophagogastroduodenoscopy (EGD) revealed a 3 cm tumour with a central ulceration and adherent blood clot protruding into the gastric antrum (figure 1A); biopsy revealed chronic gastritis. She was treated with proton-pump inhibitors, and EGD performed 1 month later …
cRGD-installed polymeric micelles loading platinum anticancer drugs enable cooperative treatment against lymph node metastasis
Authors: Jun Makino, Horacio Cabral, Yutaka Miura, Yu Matsumoto, Ming Wang, Hiroaki Kinoh, Yuki Mochida, Nobuhiro Nishiyama, Kazunori Kataoka
Journal: Journal of Controlled Release (2015)
Adeno-Associated Viral Vector-Mediated Gene Transfer of Human Blood Coagulation Factor IX Into Mouse Liver
Authors: Hiroyuki Nakai, Roland W. Herzog, J. Nathan Hagstrom, Johannes Walter, Szu-Hao Kung, Edmund Y. Yang, Shing Jen Tai, Yuichi Iwaki, Gary J. Kurtzman, Krishna J. Fisher, Peter Colosi, Linda B. Couto, Katherine A. High
Journal: Blood (1998)
Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss
Authors: Akilan Krishnamurthy, Vijay Joshua, Aase Haj Hensvold, Tao Jin, Meng Sun, Nancy Vivar, A Jimmy Ytterberg, Marianne Engström, Cátia Fernandes-Cerqueira, Khaled Amara, Malin Magnusson, Gustaf Wigerblad, Jungo Kato, Juan Miguel Jiménez-Andrade, Kerry Tyson, Stephen Rapecki, Karin Lundberg, Sergiu-Bogdan Catrina, Per-Johan Jakobsson, Camilla Svensson, Vivianne Malmström, Lars Klareskog, Heidi Wähämaa, Anca I Catrina
Journal: Annals of the Rheumatic Diseases (2015)

Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation and to identify key cellular mediators in this process.Polyclonal ACPA were isolated from the synovial fluid (SF) and peripheral blood of patients with RA. Monoclonal ACPAs were isolated from single SF B-cells of patients with RA. OCs were developed from blood cell precursors with or without ACPAs. We analysed expression of citrullinated targets and peptidylarginine deiminases (PAD) enzymes by immunohistochemistry and cell supernatants by cytometric bead array. The effect of an anti-interleukin (IL)-8 neutralising antibody and a pan-PAD inhibitor was tested in the OC cultures. Monoclonal ACPAs were injected into mice and bone structure was analysed by micro-CT before and after CXCR1/2 blocking with reparixin.Protein citrullination by PADs is essential for OC differentiation. Polyclonal ACPAs enhance OC differentiation through a PAD-dependent IL-8-mediated autocrine loop that is completely abolished by IL-8 neutralisation. Some, but not all, human monoclonal ACPAs derived from single SF B-cells of patients with RA and exhibiting distinct epitope specificities promote OC differentiation in cell cultures. Transfer of the monoclonal ACPAs into mice induced bone loss that was completely reversed by the IL-8 antagonist reparixin.We provide novel insights into the key role of citrullination and PAD enzymes during OC differentiation and ACPA-induced OC activation. Our findings suggest that IL8-dependent OC activation may constitute an early event in the initiation of the joint specific inflammation in ACPA-positive RA.
Scanning Techniques to Assess Thyroid Nodules
Authors: J L Quinn, R E Henkin
Journal: Annual Review of Medicine (1975)

Despite its nonspecificity, the thyroid scan remains an important diagnostic aid in the evaluation of the patient with a solitary thyroid nodule. Dual radionuclide thyroid imaging using 99m-Tc pertechnetate and 123-I offers useful information than either alone. The role of complementary diagnostic modalities using ultransonography and thermography looks promising but is as yet unclear.
Sentinel Node Biopsy and Occult Lesion Localization in Early Breast Cancer
Authors: G. Paganelli, G. Trifirò, L. Ravasi, C. de Cicco
Journal: Clinical Nuclear Medicine (2007)

Sentinel lymph node (SLN) localization and biopsy represent one of the most important recent developments in surgery, which has been reflected in important changes in the management of patients affected by early infiltrating breast carcinoma. Sentinel lymph node biopsy (SLNB) was first applied in melanoma patients by Morton and colleagues (Morton et al. 1992). Subsequently, the technique was proposed as a method of disease staging in breast cancer patients (Giuliano et al. 1997), so that less aggressive surgical treatment would less compromise the patient's quality of life. In fact, removal of axillary nodes in the presence of breast cancer is performed for staging and not with curative intent (Fisher et al. 2002), and axillary dissection (AD) is burdened by a significant rate of immediate and delayed possible complications such as lymphedema, paresthesia, pain and restriction of arm motion (Shaw and Rumball 1990; Kissin et al. 1986). In this context, SLNB has been proposed as an alternative to routine axillary clearance for nodal status determination.
Regulation of Glutaminase Activity and Glutamine Metabolism
Authors: Norman P. Curthoys, Malcolm Watford
Journal: Annual Review of Nutrition (1995)

Glutamine is synthesized primarily in skeletal muscle, lungs, and adipose tissue. Plasma glutamine plays an important role as a carrier of nitrogen, carbon, and energy between organs and is used for hepatic urea synthesis, for renal ammoniagenesis, for gluconeogenesis in both liver and kidney, and as a major respiratory fuel for many cells. The catabolism of glutamine is initiated by either of two isoforms of the mitochondrial glutaminase. Liver-type glutaminase is expressed only in periportal hepatocytes of the postnatal liver, where it effectively couples ammonia production with urea synthesis. Kidney­type glutaminase is abundant in kidney, brain, intestine, fetal liver, lymphocytes, and transformed cells, where the resulting ammonia is released without further metabolism. The two isoenzymes have different structural and kinetic properties that contribute to their function and short-term regulation. Although there is a high degree of identity in amino acid sequences, the two glutaminases are the products of different but related genes. The two isoenzymes are also subject to long-term regulation. Hepatic glutaminase is increased during starvation, diabetes, and feeding a high-protein diet, whereas kidney-type glutaminase is increased only in kidney in response to metabolic acidosis. The adaptations in hepatic glutaminase are mediated by changes in the rate of transcription, whereas kidney-type glutaminase is regulated at a posttranscriptional level.
Analysis of <i>ESR1</i> mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer
Authors: Gaia Schiavon, Sarah Hrebien, Isaac Garcia-Murillas, Rosalind J. Cutts, Alex Pearson, Noelia Tarazona, Kerry Fenwick, Iwanka Kozarewa, Elena Lopez-Knowles, Ricardo Ribas, Ashutosh Nerurkar, Peter Osin, Sarat Chandarlapaty, Lesley-Ann Martin, Mitch Dowsett, Ian E. Smith, Nicholas C. Turner
Journal: Science Translational Medicine (2015)

ESR1 mutations evolve during the treatment of metastatic breast cancer.
Small Molecule T315 Promotes Casitas B-Lineage Lymphoma–Dependent Degradation of Epidermal Growth Factor Receptor via Y1045 Autophosphorylation
Authors: Kuo-Yen Huang, Shih-Han Kao, Wen-Lung Wang, Chi-Yuan Chen, Tzu-Hung Hsiao, Santosh B. Salunke, Jeremy J. W. Chen, Kang-Yi Su, Shuenn-Chen Yang, Tse-Ming Hong, Ching-Shih Chen, Pan-Chyr Yang
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Despite the fact that tyrosine kinase inhibitors (TKIs) have been found effective in treating patients harboring activating mutations of epidermal growth factor receptor (EGFR), an acquired secondary mutation, T790M, which lowers the affinity to TKIs, can lead to EGFR TKI resistance after this standard treatment.To evaluate the effect of small molecule T315 on EGFR degradation and its therapeutic efficacy in vitro and in vivo.Lung adenocarcinoma cells were treated with T315, and cell proliferation and apoptotic proportion were determined by the CellTiter 96 AQueous MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay and flow cytometry. The effects of T315 on EGFR mRNA and protein levels, autophosphorylation, ubiquitination, and degradation were evaluated by real-time polymerase chain reaction and Western blot, respectively. Direct targeting of T315 to EGFR was confirmed by the in vitro kinase assay and mass spectrometry. Finally, the preclinical effect of T315 was validated in the murine xenograft model in combination with a second-generation TKI, afatinib.We identified T315 as a novel, potent small molecule for suppressing cancer cell proliferation in vitro and in vivo. The therapeutic effect was verified after T315 was combined with a second-generation TKI, afatinib, compared with a single drug administration. We found a new mechanism of action, in that T315 appears to directly bind EGFR and triggers EGFR-Y1045 autophosphorylation, whereby its degradation is triggered through the ubiquitin-proteasome pathway.Our evidence suggests that T315 is a novel class of anticancer drug that is able to inhibit the growth of EGFR-TKI-resistant lung adenocarcinoma cells by inducing the degradation of EGFR.
Machine Learning in Medicine
Authors: Rahul C. Deo
Journal: Circulation (2015)

Spurred by advances in processing power, memory, storage, and an unprecedented wealth of data, computers are being asked to tackle increasingly complex learning tasks, often with astonishing success. Computers have now mastered a popular variant of poker, learned the laws of physics from experimental data, and become experts in video games - tasks that would have been deemed impossible not too long ago. In parallel, the number of companies centered on applying complex data analysis to varying industries has exploded, and it is thus unsurprising that some analytic companies are turning attention to problems in health care. The purpose of this review is to explore what problems in medicine might benefit from such learning approaches and use examples from the literature to introduce basic concepts in machine learning. It is important to note that seemingly large enough medical data sets and adequate learning algorithms have been available for many decades, and yet, although there are thousands of papers applying machine learning algorithms to medical data, very few have contributed meaningfully to clinical care. This lack of impact stands in stark contrast to the enormous relevance of machine learning to many other industries. Thus, part of my effort will be to identify what obstacles there may be to changing the practice of medicine through statistical learning approaches, and discuss how these might be overcome.
Improving Value in Health Care — Against the Annual Physical
Authors: Ateev Mehrotra, Allan Prochazka
Journal: New England Journal of Medicine (2015)

Interview with Drs. Allan Goroll and Ateev Mehrotra on whether the annual physical should be retained, eliminated, or modified for 21st-century realities. (15:51)Download Annual physicals do not reduce morbidity or mortality, and they waste time and money. To address their overuse, relationship-building visits could be created, preventive care could be updated in other ways, and reimbursement could be changed accordingly.