tbuckley/cabot-search huggingface dataset:
Cell-Cycle Associated Transcriptional Regulation of Ribonucleotide Reductase in L1210 Leukemia Cells and Drug-Resistant Variants
Authors: C E Johnson, K Hughes, J G Cory
Journal: Cancer Communications (1991)

Previous studies from this laboratory have shown that the steady-state levels of the mRNA for the non-heme iron (NHI) subunit of ribonucleotide reductase were markedly elevated in hydroxyurea-resistant L1210 cell lines with minimal changes in the mRNA levels for the effector-binding (EB) subunit. In the present study, wild-type L1210 cells and their drug-resistant variants [hydroxyurea-resistant (HU-7); deoxyadenosine-resistant (Y-8); and deoxyadenosine/pyrazoloimidazole-resistant (ED2)] were synchronized by EGTA treatment in the G0/G1-phase of the cell cycle. Upon the addition of CaCl2, the cells reentered the cell cycle. The steady-state levels and the transcriptional rates of the mRNAs for the EB subunit and glyceraldehyde-3-phosphate dehydrogenase were measured and found to be similar in the drug-resistant variants compared to the wild-type cells. While the steady-state level of the mRNA for the NHI subunit was increased 35-fold in the HU-7 cell line, the transcription rate was increased only 7-fold. The increase in the transcription rate did not account for the large increase in the steady-state level. These data indicate that the increased steady-state level of the mRNA for the NHI subunit in the HU-7 L1210 cell line was not due to cell-cycle differences and that post-transcriptional processing and/or stability may play a role as well.
Case 1-1962
Authors: Vincent P. Dole
Journal: New England Journal of Medicine (1962)

IntroductionDr. Paul D. White: When the Scientific Symposia Committee began to arrange the program for this occasion, it was perfectly obvious that we must have a clinicopathological conference, for which this hospital is justifiably famous and which is at the present time becoming popular all over the world. Without more ado I shall introduce Dr. Benjamin Castleman, the successor of many noted pathologists in this hospital.Dr. Benjamin Castleman: Before proceeding with the case today I should like to say a few words about the history of the clinicopathological conference. I am sure that very few people realize that . . .
AB0518 Clinical Relevance of the Activity of P-Glycoprotein on Peripheral Blood Mononuclear Cells and Polymorphonuclear Neutrophils to Methotrexate in Patients with Systemic Lupus Erythematosus
Authors: C. Mendoza-Pinto, M. García Carrasco, S. Macías Díaz, S. Méndez Martínez, P. Soto Santillán, B. Pérez Romano, E.O. Guzmán Ruiz, A. Ruiz Arguelles
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previous studies have reported that methotrexate is effluxed from cells by several transmembrane proteins, including P glycoprotein (P-gp). Moreover, various studies have examined the relationship between disease activity and P-gp expression levels/function in systemic lupus erythematosus (SLE) patients. Nonetheless, the role of P-gp activity in SLE patients receiving methotrexate has not previously been evaluated. <h3>Objectives</h3> To investigate the relationship between P-gp activity on peripheral blood leukocytes from SLE patients with lupus arthritis and clinical response to methotrexate. <h3>Methods</h3> Mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN) were isolated from SLE patients (≥4 of the ACR classification criteria) with joint manifestations who had received methotrexate and corticosteroids (≥15 mg). Methotrexate responders and non-responders were compared according to the Clinical Disease Activity Index (CDAI) score. A flow cytometric daunorrubicin- efflux assay was made in peripheral blood leukocytes to determine the P-gp activity. <h3>Results</h3> Thirty-two patients were included: 34.4% had responded to methotrexate and 65.6% had not. The mean relative fluorescence unit (RFU) of both MNC and PMN were significantly lower in patients with a good response compared with those without good response (7.0±4.3 vs. 9.6±3.8; p=0.4 and 4.2±3.5 vs. 7.6±4.0; p=0.004. The prevalence of low fluorescence levels (&lt;5 RFU), which signifies higher P-gp activity of both MNC and PMNC was higher in methotrexate responders compared to non-responders, 27.3% vs. 4.8% (p=0.10) and 81.8% vs. 23.8% (p=0.003), respectively. <h3>Conclusions</h3> In patients with SLE, P-gp activity with clinical response to oral methotrexate treatment led to down P-gp activity. Further studies are required to determine the mechanisms behind this finding and whether P-gp activity mediates alterations in the efficacy of methotrexate. <h3>References</h3> Carneiro JR, Sato EI. Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol. 1999; 26: 1275–9. Tsujimura S, Saito K, Nakayamada S, et al. Clinical relevance of the expression of P-glycoprotein on peripheral blood lymphocytes to steroid resistance in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2005; 52: 1676–1683. Lu MC, Lai NS, Li KJ, et al. Increased multidrug resistance-associated protein activity in mononuclear cells of patients with systemic lupus erythematosus. Clin Exp Rheumatol. 2008; 26: 638-645. <h3>Acknowledgements</h3> We would like to thank David Buss for his valuable guidance and advice during this project. <h3>Disclosure of Interest</h3> None declared
THU0257 Brucella Spondylodiscitis: A Study of Nineteen Cases
Authors: R. Tekaya, M. Haj Tayeb, N. El Amri, H. Sahli, O. Saidane, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Brucellosis incidence has declined in developped countries, nevertheless it remains endemic in certains regions. Spondylodiscitis is the most frequent localisation of brucellosis infections complications, ranging from 30% to 85% according to cases series. <h3>Objectives</h3> The aim of our study is to report the clinical and bacteriological features of this disease as well as its therapeutic profile. <h3>Methods</h3> Retrospective study witch included medical records of patients treated for brucellar spondylodiscitis during the fifteen past years (2000–2014). <h3>Results</h3> Nineteen cases were collected (12 males/ 7 females). Mean age was 52 years [rang 36 to 75]. All patients had at least a risk factor: exposed occupation in 6 cases, and unpastorized milk consumption in 12 cases). The following symtoms were observed: inflammatory back pain (14 cases), inflammatory dorsal pain (4 cases), raduculalgia with neurological signs were (1 cases), weight loss (13 cases), fever (14 cases), night sweating (4 cases), C Reactive protein was increased in 2 cases. Lymphopenia was noted in 1 case. Wright serology was positive in all cases. Standard X-ray showed narrowing in disc space in 5 cases, endplate destuction in 9 cases and bone condensation in 3 cases. MRI performed in 14 cases, showed Low signal on T1 weighted images and high signal on T2 weighted images of the vertebral bodies and intervertebral disc. Moreover it revealed epidural extension (5 cases) abcess formation (2 cases) and psoas abcess (6 cases). All patients were treated by association of antibiotics (doxycicline and rifampicin) for 2 to 3 months. Evolution was farorable with resolution of pain, normalization of biological inflammation and slow radiologic reconstruction in 10 cases. For one patient treatment was prolongated to one year due to the persistance of an epiduritis in the follow-up MRI. <h3>Conclusions</h3> Prognosis of brucellar spondylodiscitis seems good under appropriate treatment. Nevertheless primary prevention is still necessary especially in countries where brucellosis is endemic. <h3>Disclosure of Interest</h3> None declared
Narcolepsy: preliminary retrospective study of psychiatric and psychosocial aspects
Authors: R R Krishnan, M R Volow, P P Miller, S T Carwile
Journal: American Journal of Psychiatry (1984)

A review of the charts of 24 ambulatory male veterans with narcolepsy or narcolepsy/cataplexy showed an impressive number of psychiatric and psychosocial difficulties in these patients, such as poor adjustment to the illness, high unemployability, and disturbed intrafamily relationships. Sixteen of the patients had psychiatric disorders according to DSM-III criteria, including adjustment disorder, major depressive episode, alcohol dependence, and personality disorder, but excluding any type of psychotic disorder. The study suggests that narcoleptic/cataplectic patients have more of these difficulties than narcoleptic patients do.
Lymphoma cell line (FL-18) and Epstein-Barr virus-carrying cell line (FL-18-EB) obtained from a patient with follicular lymphoma: monoclonal derivation and different properties
Authors: S Doi, H Ohno, E Tatsumi, Y Arita, H Kamesaki, S Fukuhara, M Nishikori, H Miwa, K Kita, M Hatanaka
Journal: Blood (1987)
Case 38-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Peter M. Yurchak, Eugene J. Mark
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 64-year-old man was admitted to the hospital because of pulmonary hypertension.The patient was a former fire chief, who had enjoyed excellent health and an athletic life style until five years earlier, when fatigue and dyspnea on exertion developed gradually, and he discontinued playing singles tennis. At the same time he began to experience occasional bouts of aching pain to the right of the sternum on climbing stairs. Several months later he fainted after fighting a fire. Four years before entry a stress test was begun but was halted because of the occurrence of numerous premature . . .
Response to nilotinib in chronic myelogenous leukemia patients in chronic phase (CML-CP) according to BCR-ABL mutations at baseline #7060
Authors: G. Saglio, J. Radich, D. Kim, G. Martinelli, S. Branford, M. Mueller, S. Soverini, Y. Shou, A. Hochhaus, T. Hughes
Journal: Journal of Clinical Oncology (2008)

7060 Background: Nilotinib is a potent and highly-selective BCR-ABL inhibitor approved in the US and Europe for the treatment of patients (pts) with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) and accelerated phase (AP) who are resistant or intolerant to prior therapy including imatinib. Methods: This subanalysis of a phase 2 study of nilotinib in imatinib-resistant or-intolerant CML-CP pts assessed the occurrence of baseline BCR-ABL mutations and their impact on treatment outcome following 12 months of therapy. The BCR-ABL kinase domain (amino acid 230–490) was amplified and mutations identified by direct sequencing that allowed for detection of > 20% minor alleles. Results: Of the 275 pts with mutation data available, 113 (41%) had BCR-ABL mutations at initiation of nilotinib therapy. Amongst imatinib-resistant patients, the frequency of mutations at initiation was 56%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 42%, and major molecular response (MMR) in 25% of pts without baseline mutations, versus 50%, 32%, and 21% of pts with mutations, respectively, among the imatinib-resistant pts. Response rates in pts with mutations of < =150 nM cellular IC50 (M244V, L248V, G250E, Q252H, E275K, D276G, F317L, M351T, E355A, E355G, L387F, F486S) and with mutations of unknown IC50 values had comparable response rates to those for pts without baseline mutations: MCyR were 62% and 58%, respectively, and CCyR were 40% and 42%, respectively. For patients (n=26) with less sensitive BCR-ABL mutations (in vitro cellular IC50 > 150 nM), MCyR was achieved in 1 of 8 pts (13%) with Y253H, 3 of 8 pts (38%) with E255K/V, and 1 of 10 pts (10%) with F359C/V. None of these patients achieved CCyR. Conclusions: A significant proportion of imatinib-resistant pts with BCR-ABL mutations at baseline respond to imatinib. Pts with sensitive BCR-ABL mutations exhibited response rates on nilotinib therapy comparable to those for patients with no baseline mutations. Less sensitive mutations represented <15% of the cohort and may be associated with less favorable responses. Larger cohort and longer follow up are required to validate these findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Merck, Novartis Bristol-Myers Squibb, Merck, Novartis Bristol-Myers Squibb, Il Yang Pharmaceutical Company, Innovive Pharmaceuticals, Merck, Novartis, Wyeth
Childhood Leukemia
Authors: Sharon Parmet
Journal: JAMA (2004)

Childhood LeukemiaL eukemia is cancer of the white blood cells, which play an important role in fighting infections.All blood cells are produced in the bone marrow-the spongy tissue in the center of bones.When a child has leukemia, too many abnormal early-stage white blood cells are produced.This can interfere with the production of red blood cells (which carry oxygen) and platelets (which help blood clot).The abnormal white blood cells can damage the function of many different organs and tissues and can also invade the spinal fluid.Leukemia can occur in children of all ages but affects boys more often than girls.Leukemia is believed to be caused by genetic mutations-abnormal changes in the genes of blood cells.Leukemia is not contagious and does not generally run in families.The January 28, 2004, issue of JAMA includes an article about clinical trials for children with leukemia.
FRI0018 CAMK4 Inhibition Prevents Recruitment of IL-17 Producing Cells to Target Organs Through CCR6/CCL20 Axis in TH17 Driven Inflammatory Diseases
Authors: T. Koga, K. Otomo, M. Mizui, N. Yoshida, J.C. Crispin, A. Kawakami, G.C. Tsokos
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> IL-17 producing T helper (Th17) cells have been closely associated with the development of organ damage in inflammatory and autoimmune diseases. We have previously reported that Calcium/calmodulin-dependent protein kinase IV (CaMK4) plays a crucial role in Th17 cell differentiation invitro and invivo and suggested that CaMK4 inhibition ameliorates clinical and pathological findings in experimental autoimmune encephalomyelitis (EAE) and MRL/lpr mice (1). We have also shown that Il-17 is important in the expression of anti-glomerular basement membrane Ab-induced glomerulonephritis (AIGN) (2). However, the effect of CaMK4 on recruitment of pathogenic T cells to target tissues in inflammatory settings has not been studied. <h3>Objectives</h3> The aim of this study is to determine the role of CaMK4 in the infiltration of inflammatory cells to target tissues and to explore its mechanism. <h3>Methods</h3> We induced experimental AIGN in <i>Camk4</i> sufficient or deficient mice and compared the kidney injury including the number of IL-17 producing cells and the expression of CCR6 and CCL20 in both groups. We also evaluated the effect of KN-93, a compound of CaMK4 antagonist in this AIGN model. <h3>Results</h3> <i>Camk4</i> deficient mice displayed less glomerular injury and less proteinuria at day 14 and at day 21 after induction of AIGN. The expression of CCR6 and CCL20 in inflamed kidney is lower in <i>Camk4</i> deficient mice. Kidney infiltration by Th17 producing CD4<sup>+</sup> T cells was decreased significantly in <i>Camk4</i> deficient mice, suggesting that CaMK4 facilitated AIGN damage by promoting local inflammatory cells accumulation. In line with these observations, KN-93 treatment improved clinical and pathological finings in mice induced AIGN at dose dependent manner. <h3>Conclusions</h3> Collectively, our results indicate that CaMK4 inhibition might be a novel therapeutic strategy of Th17 cells-mediated inflammatory diseases. <h3>References</h3> CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance. Koga T, Hedrich CM, Mizui M, Yoshida N, Otomo K, Lieberman LA, Rauen T, Crispín JC, Tsokos GC. J Clin Invest. 2014 May 1;124(5):2234-45. Cutting edge: protein phosphatase 2A confers susceptibility to autoimmune disease through an IL-17-dependent mechanism.Crispín JC, Apostolidis SA, Rosetti F, Keszei M, Wang N, Terhorst C, Mayadas TN, Tsokos GC.J Immunol. 2012 Apr 15;188(8):3567-71. <h3>Disclosure of Interest</h3> None declared
FRI0172 Commonplace Though not Approved – Monotherapy with Biologics. Data from the Austrian Bioreg Registry
Authors: M. Herold, G. Eichbauer-Sturm, R. Puchner, B. Rintelen, F. Singer, B. Leeb
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The Austrian <i>BioReg</i> registry (http://www.bioreg.at) was initiated in 2009. Patients treated with one of the nine biologics (abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab) approved in Austria can be included. Patients with ongoing biologic therapy as well as biologic-naïve patients starting biologic therapy can be included. Further documentation is recommended about every six months. Meanwhile, 1493 patients (rheumatoid arthritis (RA) n=857, ankylosing spondylitis (SpA) n=362, psoriatic arthritis (PsA) n=239, treatments out of label n=35) have been documented. Most biologics are approved for treatment of RA only in combination with methotrexate (MTX). <h3>Objectives</h3> The aim of this evaluation was to elucidate the percentage of RA patients treated with biologic monotherapy at baseline and at control visits one, two and three years after inclusion in <i>BioReg</i>. <h3>Methods</h3> Three different patient groups were defined. Patients with data at baseline and control visit after one or two or three years ±3 months were evaluated for drug therapy at the time of inclusion and at control visit. 411 RA patients with data at baseline and after one year, 186 with data after two years and 98 with data after three years were analyzed. <h3>Results</h3> 155/411 had a biologic as monotherapy at baseline, after one year 165/411; 62/186 at baseline, 71/186 after two years; 40/98 at baseline, 43/98 after three years. At baseline 39.7% of patients received a biologic as monotherapy. The percentage of RA patients (40.1; 38.2; 43.9%) on biologic monotherapy seems to increase with time of treatment. <h3>Conclusions</h3> About forty percent of RA patients treated with a biologic receive biologics as monotherapy and not in combination with a conventional disease-modifying drug (DMARD). These data are in agreement with observations from other registries (1, 2). <h3>References</h3> Emery P et al. Ann Rheum Dis. 2013;72:1897-904 Zhang J et al. Arthritis Care Res 2014 doi: 10.1002/acr.22510 <h3>Acknowledgements</h3> <i>BioReg</i> is supported by an unlimited industrial grant. <h3>Disclosure of Interest</h3> None declared
Drug-Induced Hemolytic Anemia
Authors: Hideo Terada
Journal: JAMA (1963)

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
Neoplasms in Mice Inoculated with a Tumor Agent Carried in Tissue Culture2
Authors: Sarah E. Stewart, Bernice E. Eddy, Ninette Borgese
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article Neoplasms in Mice Inoculated with a Tumor Agent Carried in Tissue Culture Get access Sarah E. Stewart, Sarah E. Stewart Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernice E. Eddy, Bernice E. Eddy Search for other works by this author on: Oxford Academic PubMed Google Scholar Ninette Borgese Ninette Borgese Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 6, June 1958, Pages 1223–1243, https://doi.org/10.1093/jnci/20.6.1223 Published: 01 June 1958 Article history Received: 07 January 1958 Published: 01 June 1958
PTH-183 Upper gastrointestinal cancer red flag symptoms alone except dysphagia do not predict the presence of upper gastrointestinal tract cancer: implications for practice
Authors: S Sultan, BM Shandro, S Friday, B Wang, M Suleman, J Cooney, P Paskaran, S Gupta, M Mendall
Journal: Gut (2015)

<h3>Introduction</h3> The epidemiology of upper gastrointestinal (UGI) cancer is rapidly changing. Current guidelines for red flag symptoms for UGI cancer were drawn up using evidence from a past age. With the exception of dysphagia, many of the symptoms are non-specific for UGI cancer in particular dyspepsia, particularly with the rapidly declining prevalence of H. pylori and its associated gastric cancers. <h3>Aims</h3> To determine the value of individual UGI cancer red flag symptoms alone or in combination in predicting the presence of UGI and non-UGI cancers. <h3>Method</h3> Our routine practice is to investigate all patients referred under the urgent suspected cancer (USC) pathway with an oesophagogastroduodenoscopy (OGD) and a computed tomography (CT) scan if over 50 years of age and symptoms are not purely oesophageal. A retrospective case review between October 2013 to March 2014 of all referrals on the USC pathway to our district general hospital with a case review of all the UGI cancers detected by our service over a one year period (October 2013–2014). Clinical follow-up after referral was a minimum of 11 months. <h3>Results</h3> 391 patients (20–96 age range) were seen under the USC pathway between October 2013–March 2014. In total 372 and 177 patients were investigated with an OGD and a CT scan respectively; 289 and 161 respectively were patients over the age of 50. 19 cancers were detected giving a detection rate of 4.75%. Of those only nine were UGI cancers (three gastric, six oesophageal). Other cancers found included three colorectal, one pancreatic, three lung, one cholangiocarcinoma, one ovarian and one peritoneal. The table shows the symptoms distribution for both UGI and non-UGI cancers. Isolated red flag symptoms had poor predictive power. Weight loss and dysphagia in combination with other symptoms had the best predictive value. There was a similar number of UGI cancers (23) and non UGI cancers (19). Analysis of all UGI cancers n = 47 over the course of one year not necessarily presenting through the USC route (October 2013–2014) revealed that isolated dyspepsia was found in only two of 47 patients compared to iron deficiency anaemia, weight loss and dysphagia which were the sole presenting symptoms in seven, four and three patients respectively, reinforcing the findings from the USC referrals. <h3>Conclusion</h3> In modern times, isolated UGI cancer red flag symptoms particularly dyspepsia are poorly predictive of UGI cancer, and equally well predict the presence of cancer outside the UGI tract. CT scanning should be a routine part of evaluation of UGI cancer referrals in the over 50’s. <h3>Disclosure of interest</h3> None Declared.