tbuckley/cabot-search huggingface dataset:
SC-02 * MODELING PEDIATRIC GBM USING NEURAL STEM CELL-DERIVED TUMORS WITH DIVERGENT BEHAVIOR
Authors: O. R. Lindberg, A. McKinney, J. R. Engler, J. J. Phillips
Journal: Neuro-Oncology (2015)

Pediatric GBM can exhibit a diversity of cell behaviors and responses to therapy despite similar oncogenic drivers. The reasons for this are often unclear. Using a murine model for GBM based on the oncogenic transformation of neural progenitor cells we sought to generate tumors with diverse cell behaviors despite being driven by a common oncogene. Using in vivo tumor phenotype as evidence of divergent tumor behavior, we isolated two tumor lines with different phenotypes. Tumor progenitor cell (TPC) line-A was highly proliferative and resulted in rapid lethality (median overall survival of 22 days) vs. TPC-B that was less proliferative and exhibited a more prolonged survival (median overall survival of 33 days). Interestingly, TPC-A invaded in perivascular fashion in vivo. In contrast, TPC-B tumors invaded diffusely, as single cells. Transcriptional profiling revealed an enrichment of mesenchymal GBM subtype genes in TPC-A (normalized enrichment score of 1.5) and proneural GBM subtype genes in TPC-A (normalized enrichment score of 2.6). Consistent with the gene expression data, TPC-A exhibited increased activation of Stat3 (pY705) relative to TPC-B. Furthermore, while both clones expressed hEGFRvIII, TPC-A cells showed higher levels of EGFR activation (pY1173 and pY1068), than TPC-B cells. In vitro, TPC-A expanded at a higher rate than TPC-B and expressed Prominin-1 (CD133). TPC-B cells were Prominin-1 negative, but more prone to adhere to ECM components than TPC-A, and invaded more extensively in vitro. Moreover, under differentiation conditions, TPC-A failed to differentiate and continuously proliferated. TPC-B differentiated to cells of neuronal, astrocytic, and oligodendrocytic lineages. Interestingly, these lines also exhibited differential response to therapy. In the current project we demonstrate how transduction of neurospheres can be used to generate tumor lines with vastly different cell behaviors, reflective of different pediatric GBM, and that these lines are useful for both mechanistic and preclinical studies.
Users' Guides to the Medical Literature
Authors: Robert S. A. Hayward, Mark C. Wilson, Sean R. Tunis, Eric B. Bass, Gordon Guyatt
Journal: JAMA (1995)

<h3>CLINICAL SCENARIO</h3> You are relieved to find that the last patient in your busy primary care clinic is a previously well 48-year-old woman with acute dysuria. There has been no polydipsia, fever, or hematuria; the physical examination reveals suprapubic tenderness; and urinalysis shows pyuria but no casts. You arrange cultures and antibiotic treatment for a lower urinary tract infection. On her way out the door, your patient observes that her friend has just started taking "female hormones," and she wonders whether she should too. Her menstrual periods stopped 6 months ago and she has never had cervical, ovarian, uterine, breast, or cardiovascular problems, but her mother had a mastectomy at age 57 for postmenopausal breast cancer. You give the same general advice you have offered similar patients in the past, but suggest that the matter be discussed at greater length when she returns after completing the antibiotic treatment. Later, as
Alcohol in the body
Authors: Janusz Knepil
Journal: BMJ (2005)

Family history of breast cancer Referral guidelines changed after acceptance of 10 minute consultationEditor-In their 10 minute consultation on family history of breast cancer Lucassen and Watson drew attention to the recently published guidelines from the National Institute for Clinical Excellence (NICE) on familial breast cancer. 1 2 It is unfortunate that the referral criteria were changed between the acceptance of this article in December 2003 and the final published guidelines in June 2004, which would result in the referral of the patient highlighted in the article for potential mammography screening, rather than for her reassurance.Women aged 40-49 years at moderate risk of breast cancer are entitled to annual mammograms. 2 The definition of moderate risk was based on a risk of at least 3% over the 10 year period from the age of 40 to 50.Available evidence, particularly from combined analyses of case-control studies of familial risks, 3 indicates that a woman reaches this category with a first degree relative (mother or sister) with breast cancer when younger than 40 years or two relatives on the same side of the family (one first degree and one second degree or two first degree) diagnosed at any age.The latter category differs from the draft NICE guidelines and previous referral criteria, which required that the two relatives be diagnosed at an average age of less than 60. 4 This age restriction was removed because it could not be justified on the basis of the available data.It should be noted, however, that referral on the basis of two elderly close relatives is likely to be restricted to the age groups of 30-49, with referral of only high risk groups (for example, two affected relatives diagnosed at an average age of less than 50 years) outside this age group.
Joint Problems and Cystic Fibrosis—Reply
Authors: Michael P. Boyle
Journal: JAMA (2008)

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
The Parathyroid Polyhormones: New Concepts in the Spectrum of Peptide Hormone Action*
Authors: LAWRENCE E. MALLETTE
Journal: Endocrine Reviews (1991)

WE WILL review a series of studies in the field of calcium metabolism which, over the last 3 yr, have added a new complexity to our concepts about peptide hormone action. The traditional view of peptide hormone action holds that a peptide hormone bears a region that is configured to possess high affinity for a receptor on the membrane of the target cell. Interaction with that receptor alters other membrane components to initiate a cascade of intracellular events, mediated by changes in intracellular AMP, calcium, phosphatidyl inositol metabolites, or other second messengers. An increased ambient concentration of the hormone will cause an increased occupancy of receptors and greater action on the target cell. The organ specificity of the hormone is determined by the spectrum of cell types that bear the appropriate receptor. Additional orders of complexity were added by the findings that receptor number can vary (exposure to the hormone, for example, can decrease the number of receptors), that postreceptor events may become refractory for a time after an episode of increased receptor occupancy, that other peptides can sometimes interact with a given hormone's receptor (insulin-like growth factors, for example), and that a hormone may have more than one class of receptors.
IMPACT OF DIABETES MELLITUS ON CORONARY PLAQUE PROGRESSION AND CHANGE IN PLAQUE COMPOSITION IN NON-CULPRIT LESION UNDER OPTIMAL MEDICAL TREATMENT
Authors: Kuninobu Kashiyama, Shinjo Sonoda, Yoshitaka Muraoka, Yoshiyuki Suzuki, Yuki Tsuda, Masaru Araki, Masahiro Okazaki, Yutaka Otsuji
Journal: Journal of the American College of Cardiology (2014)
Mechanisms of Pulsus Alternans
Authors: KEITH E. COHN, HAROLD SANDLER, E. W. HANCOCK
Journal: Circulation (1967)

The mechanisms of pulsus alternans were studied in three patients by cineangiographic determinations of left ventricular volume. In two patients with left ventricular disease, pulsus alternans occurred without detectable variation in left ventricular enddiastolic pressure (LVEDP) or end-diastolic volume (EDV), although in the second case these values did alternate in the initial postextrasystolic beats. Another patient with normal left ventricular function had brief postextrasystolic pulsus alternans associated with LVEDV alternations. Twenty-nine patients with valvular aortic stenosis who showed pulsus alternans during left heart catheterization were also studied. Persistent alternation in LVEDP occurred in eight, with transient LVEDP alternation appearing after extrasystoles in 22 cases. Cardiac cycle length and diastolic interval alternation occurred inconsistently.
Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study
Authors: Oliver P Stannus, Graeme Jones, Leigh Blizzard, Flavia M Cicuttini, Changhai Ding
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To determine the association between inflammatory markers and change in knee pain over 5 years. <h3>Methods</h3> A total of 149 randomly selected subjects (mean 63 years, range 52–78; 46% female) was studied. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor alpha (TNF–α) and interleukin (IL)-6 were measured at baseline and 2.7 years later. Knee pain was recorded using the Western Ontario and McMasters osteoarthritis index questionnaire at baseline and 5 years later. Knee radiographic osteoarthritis of both knees was assessed at baseline, and knee bone marrow lesions, joint effusion and cartilage defects were determined using T1 or T2-weighted fat saturated MRI. <h3>Results</h3> After adjustment for confounding variables, baseline hs-CRP was positively associated with change in total knee pain (β=0.33 per mg/l, p=0.032), as well as change in the pain at night in bed (β=0.12 per ml/pg, p=0.010) and while sitting/lying (β=0.12 per ml/pg, p=0.002). Change in hs-CRP was also associated with change in knee pain at night and when sitting/lying (both p&lt;0.05). Baseline TNFα and IL-6 were associated with change in pain while standing (β=0.06 per ml/pg, p=0.033; β=0.16 per ml/pg, p=0.035, respectively), and change in TNFα was positively associated with change in total knee pain (β=0.66 ml/pg, p=0.020) and change in pain while standing (β=0.26 ml/pg, p=0.002). Adjustment for radiographic osteoarthritis or MRI-detected structural abnormalities led to no or minor attenuation of these associations. <h3>Conclusion</h3> Systemic inflammation is an independent predictor of worsening knee pain over 5 years.
MISUSE OF AMERICAN MEDICAL ASSOCIATION DATA
Authors: FRANK G. DICKINSON
Journal: JAMA (1949)

Dr. Channing Frothingham, Chairman of the Committee for the Nation's Health, stated recently: The AMA's own statistics show that 80 per cent of the population—all those with incomes under $5,000 a year—are not able to meet the expenses of serious illness out of their own resources.1Testifying before the Senate Committee on Education and Labor, Dr. Allan M. Butler, associate professor of pediatrics at the Harvard Medical School, said, The American Medical Association agrees that patients whose family income is $3,000 per year cannot pay the costs of serious illness.2Seymour E. Harris, professor of economics, Harvard University, made the following statement before the Senate Subcommittee of the Committee on Labor and Public Welfare, Actually in 1939 the AMA estimated that families with incomes under $3,000 could not afford a serious illness. This is the equivalent of $5,000 today and, therefore, the AMA estimate suggests help for 80
Follow-up of Patients With Breast Cancer
Authors: Giorgio Cocconi
Journal: JAMA (1994)

To the Editor.  —Two articles recently published inThe Journal 1,2 indicate that conservative follow-up (ie, history and physical examinations every 3 months and mammography once a year) for patients with operable breast cancer is as good as a more intensive and expensive approach that would include periodic chest radiography, bone scanning, and in one study, liver ultrasonography. Overall survival and quality of life did not differ between the two types of follow-up. Disease-free survival was shorter in one study with intensive monitoring as a result of earlier detection of metastasis. Overall, the conclusions reached by the authors are supported by the findings.  However, I believe that several issues should be considered that may undermine the universality of these conclusions. The findings reported in these two randomized trials are not surprising, since at present, chemotherapy and hormonal therapy for metastatic breast carcinoma are palliative, and therefore, it is unlikely that
Abstract C2: Nuclear factor I/C collaborates with androgen receptor in transcription regulation in prostate cancer
Authors: Chong Yang, Kern Rei Chng
Journal: Cancer Research (2012)

Abstract Androgen receptor (AR) plays an important role in mediating the transcriptional regulatory network directing prostate cancer initiation, development and progression. In order to gain insights into the AR-dependent transcriptional regulatory network, we utilized Chromatin Immunoprecipitation-sequencing (ChIP-Seq) and generated genome-wide binding maps of AR in the LNCaP prostate cancer cell line. From our bioinformatic analyses of AR binding sites (ARBS), we found an enrichment of motifs belonging to the NFI family. We demonstrate that one member of the NFI family, NFIC, which has been shown to be over-expressed in clinical prostate tumors, overlaps with a large fraction of ARBS across the genome. Surprisingly, the recruitment of NFIC was independent of DHT treatment, indicating NFIC as a potential pioneer factor. Moreover, we showed NFIC was required for the global modulation of AR-dependent target genes including KLK2, KLK3, and TMPRSS2. Finally, we found that AR and NFIC co-associated genes are preferentially involved in cellular movement and apoptosis. Together, our results suggest NFIC is a novel collaborative factor in AR-mediated transcription. Citation Format: Chong Yang, Kern Rei Chng. Nuclear factor I/C collaborates with androgen receptor in transcription regulation in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C2.
Genomic analysis of different clonal evolution in a twin pair with t(12;21) positive acute lymphoblastic leukemia sharing the same prenatal clone
Authors: S Bungaro, J Irving, R Tussiwand, R Mura, L Minto, C Molteni, M Citterio, A Hall, A Biondi, G Cazzaniga
Journal: Leukemia (2007)
Endothelial Cell–Specific Reactive Oxygen Species Production Increases Susceptibility to Aortic Dissection
Authors: Lampson M. Fan, Gillian Douglas, Jennifer K. Bendall, Eileen McNeill, Mark J. Crabtree, Ashley B. Hale, Anna Mai, Jian-Mei Li, Martina A. McAteer, Jurgen E. Schneider, Robin P. Choudhury, Keith M. Channon
Journal: Circulation (2014)

Increased production of reactive oxygen species (ROS) throughout the vascular wall is a feature of cardiovascular disease states, but therapeutic strategies remain limited by our incomplete understanding of the role and contribution of specific vascular cell ROS to disease pathogenesis. To investigate the specific role of endothelial cell (EC) ROS in the development of structural vascular disease, we generated a mouse model of endothelium-specific Nox2 overexpression and tested the susceptibility to aortic dissection after angiotensin II (Ang II) infusion.A specific increase in endothelial ROS production in Nox2 transgenic mice was sufficient to cause Ang II-mediated aortic dissection, which was never observed in wild-type mice. Nox2 transgenic aortas had increased endothelial ROS production, endothelial vascular cell adhesion molecule-1 expression, matrix metalloproteinase activity, and CD45(+) inflammatory cell infiltration. Conditioned media from Nox2 transgenic ECs induced greater Erk1/2 phosphorylation in vascular smooth muscle cells compared with wild-type controls through secreted cyclophilin A (CypA). Nox2 transgenic ECs (but not vascular smooth muscle cells) and aortas had greater secretion of CypA both at baseline and in response to Ang II stimulation. Knockdown of CypA in ECs abolished the increase in vascular smooth muscle cell Erk1/2 phosphorylation conferred by EC conditioned media, and preincubation with CypA augmented Ang II-induced vascular smooth muscle cell ROS production.These findings demonstrate a pivotal role for EC-derived ROS in the determination of the susceptibility of the aortic wall to Ang II-mediated aortic dissection. ROS-dependent CypA secretion by ECs is an important signaling mechanism through which EC ROS regulate susceptibility of structural components of the aortic wall to aortic dissection.
Sebelipase alfa over 52weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency
Authors: Vassili Valayannopoulos, Vera Malinova, Tomas Honzík, Manisha Balwani, Catherine Breen, Patrick B. Deegan, Gregory M. Enns, Simon A. Jones, John P. Kane, Eveline O. Stock, Radhika Tripuraneni, Stephen Eckert, Eugene Schneider, Gavin Hamilton, Michael S. Middleton, Claude Sirlin, Bruce Kessler, Christopher Bourdon, Simeon A. Boyadjiev, Reena Sharma, Chris Twelves, Chester B. Whitley, Anthony G. Quinn
Journal: Journal of Hepatology (2014)

Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase.Sebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals.216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected.Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184).
Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma
Authors: Andrea Zanini, Alfredo Chetta, Marina Saetta, Simonetta Baraldo, Raffaele D'Ippolito, Antonio Castagnaro, Margherita Neri, Dario Olivieri
Journal: Journal of Allergy and Clinical Immunology (2007)
Imipramine and Thioridazine in Depressed and Schizophrenic Patients
Authors: John E. Overall, Leo E. Hollister, Fred Meyer, Isham Kimbell, Jack Shelton
Journal: JAMA (1964)

Thioridazine hydrochloride and imipramine hydrochloride were compared in 68 schizophrenic and 77 depressive patients using blind controls. A computer procedure making use of pretreatment psychiatric rating profiles was used to classify patients into depressive and schizophrenic groups. In the schizophrenic sample, thioridazine was found to be significantly superior to imipramine in a number of areas. In the depressive sample, essentially no significant differences between the drugs were found, although the observed mean differences tended to favor thioridazine over imipramine in this group also. Summing across both patient samples, thioridazine was found significantly superior to imipramine in a number of symptom areas, while imipramine was superior only in reducing motor retardation.
Humoral and Genetic Factors in Thyrotoxic Graves Disease and Neonatal Thyrotoxicosis
Authors: William L. Green
Journal: JAMA (1976)

WHY IS the thyroid gland hyperactive in Graves disease? Since the demise of the theory that postulated excessive pituitary thyroid-stimulating hormone secretion, most hypotheses have included some type of stimulation by immunoglobulins or activated lymphocytes, with or without a role for an intrinsic abnormality of the thyroid gland. The presence of autoimmune phenomena in Graves disease is beyond dispute.<sup>1</sup>Many patients have demonstrable antibodies to thyroid antigens, and Graves disease has a proved familial association with the archetypal autoimmune endocrine disease, Hashimoto thyroiditis. Graves disease is unique among so-called autoimmune diseases, however, in that an immunoglobulin that has biological effects similar to those of an important hormone, thyrotrophin, is frequently present. Since the original observation that Graves sera can produce a prolonged stimulation of thyroid secretion in guinea pigs and mice, this "long-acting thyroid stimulator," or LATS, has been the object of intensive study. It is an immunoglobulin of
Differentiation of rat intestinal epithelial cells is induced by organotypic mesenchymal cells in vitro.
Authors: A Stallmach, U Hahn, H J Merker, E G Hahn, E O Riecken
Journal: Gut (1989)

Stromal-epithelial interaction is a potent driving force in the developing intestinal mucosa which ensures tissue specific cellular differentiation. The mechanisms involved are relevant to tissue renewal in adult organs yet they have not been elucidated because of the lack of appropriate in vitro models. In this study, we have investigated the interaction between intestinal mesenchymal and epithelial cells at the cellular level in vitro. Fetal rat intestinal epithelial cell colonies explanted in vitro on the 15th day of gestation, which failed to mature in plain monocultures, were reassociated in coculture with three different types of mesenchyme:fetal skin, gastric and intestinal mesenchyme. Only fetal epithelial cells cocultured with intestinal (homologous) mesenchyme acquired definite signs of differentiation within three to six days. These primitive epithelial cells were shown by electronmicroscopy to become highly polarized, connected by tight junctions and covered with a regular brush border. Three brush border enzymes were strongly expressed in homologous cocultures and their activity was sensitive to dexamethasone. In contrast, fetal epithelial cells cocultured with skin or stomach derived mesenchyme under identical conditions failed to differentiate in vitro: they remained flat, unpolarised and expressed only low enzyme activity. The unique potential of the small intestinal mesenchyme to promote intestinal epithelial differentiation is discussed.