tbuckley/cabot-search huggingface dataset:
Abstract 13801: The p.Leu167del Mutation in APOE Gene causes Autosomal Dominant Hypercholesterolemia by Down-Regulation of LDL Receptor Expression in Hepatocytes
Authors: Ana Cenarro, César Martín, Marianne Stef, Isabel de Castro-Orós, Aitor Etxebarria, Lourdes Palacios, Rocío Mateo-Gallego, Helena Ostolaza, Teresa Tejedor, Fernando Civeira
Journal: Circulation (2014)

Introduction: The p.Leu167del mutation in APOE gene has been associated to different hyperlipidemias. However, the frequency of this mutation in autosomal dominant hypercholesterolemia and the mechanism of this association is not known. Objectives: To establish the frequency of p.Leu167del mutation in APOE gene in subjects with clinical diagnosis of Autosomal Dominant Hypercholesterolemia (ADH) non-dependent of LDLR, APOB nor PCSK9 genes, and to investigate the mechanism by which this mutation associates to ADH. Methods: We selected 288 unrelated subjects with ADH non-dependent of LDLR, APOB nor PCSK9 genes, and 220 unrelated normolipidemic subjects (control group). All available family members of mutation carrier subjects were also studied. Exon 4 of APOE gene was sequenced in all subjects. VLDL and LDL were isolated from p.Leu167del carriers and E3/E3 control subjects by ultracentrifugation. Quantification of lipoprotein uptake in HepG2 and THP-1 cells and LDL receptor membrane-expression in HepG2 cells were carried out by flow cytometry. Results: In the ADH group, 9 unrelated subjects (3.1%) were carriers of the p.Leu167del mutation in APOE gene and none in the control group. Eleven family members were carriers of the mutation, 7 with isolated hypercholesterolemia and 4 with mixed hyperlipidemia. A clear co-segregation of p.Leu167del mutation with elevated plasma cholesterol levels in the families was found. VLDL isolated from p.Leu167del mutation carriers had a significantly higher uptake by HepG2 and THP-1 cells compared to VLDL isolated from E3/E3 subjects (p&lt;0.01). When increasing incubation times of HepG2 cells with VLDL from p.Leu167del carriers, the LDL receptor expression in surface membrane diminished, in contrast with the VLDL from E3/E3 subjects. When pre-incubating HepG2 cells with VLDL from p.Leu167del mutation carriers, the percentage of LDL internalisation was significantly lower than when incubating with VLDL from E3/E3 subject (p&lt;0.01). Conclusion: The p.Leu167del mutation in APOE gene is associated to ADH in 3.1% of studied subjects. The mechanism of this association is higher uptake of VLDL, down regulation of the LDLR expression and decrease of LDL internalisation in hepatocytes.
The Diagnosis of Hyperthyroidism
Authors: Maynard E. Holmes
Journal: Annals of Internal Medicine (1932)

Article1 February 1932The Diagnosis of HyperthyroidismMAYNARD E. HOLMES, M.D., F.A.C.P.MAYNARD E. HOLMES, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-8-1028 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe term hyperthyroidism has been adopted in recent years to designate a symptom complex caused by hyperactivity of the thyroid gland. In the past, patients who are now classified as having hyperthyroidism together with a large group with a similar symptomatology but not of thyroid origin, were diagnosed as having Graves' disease. Kessel1 has called attention to the latter group and applied to it the term autonomic imbalance, to designate it as a disturbance of the autonomic nervous system.Moschcowitz2is of the opinion that Graves' disease evolves from a basic neuropathic personality to its fullblown clinical form when hyperthyroidism...References1 KESSELLIEBHYMAN LCCHT: A study of exophthalmic goiter and the involuntary nervous system, Jr. Am. Med. Assoc., 1922, lxxix, 1213-1216. CrossrefGoogle Scholar2 MOSCHCOWITZ E: The nature of Graves' disease, Arch. Int. Med., 1930, xlvi, 610-629. CrossrefGoogle Scholar3 HAMILTONLAHEY BEFH: Differentiation of hyperthyroidism and heart disease from neurasthenic states, Jr. Am. Med. Assoc., 1922, lxxviii, 1793-1796. Google Scholar4 BENEDICT FG: The measurement and standards of basal metabolism, Jr. Am. Med. Assoc., 1921, lxxvii, 247-250. Google Scholar5 DUBOIS EF: Basal metabolism in health and disease, 1924, Lea and Febiger, Philadelphia, p. 104. Google Scholar6 ZIEGLERLEVINE LHBS: The influence of emotional reactions on basal metabolism, Am. Jr. Med. Sci., 1925, clxix, 68-76. CrossrefGoogle Scholar7 LANDIS C: Studies of emotional reactions; metabolic rate, Am. Jr. Physiol., 1925, lxxiv, 188-203. CrossrefGoogle Scholar8 HENRY GW: Basal metabolism and emotional states, Jr. Nerv. and Ment. Dis., 1929, lxx, 598-605. CrossrefGoogle Scholar9 BARACHDRAPER ALG: The significance of the basal metabolism determination, Jr. Am. Med. Assoc., 1925, lxxxiv, 740-745. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Syracuse, N. Y.*From the Department of Metabolism, University Hospital, Syracuse University College of Medicine.†Received for publication, June 16, 1931. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1932Volume 5, Issue 8Page: 1028-1032KeywordsAutonomic nervous systemHospital medicineHyperthyroidismThyroid ePublished: 1 December 2008 Issue Published: 1 February 1932 PDF downloadLoading ...
Use of mutational profiling of metastatic ER+/HER2- breast cancers and the coexistence of KRAS, MET, BRAF, and FGFR3 with PIK3CA mutations.
Authors: Debora Fumagalli, Roberto Salgado, Carmen Criscitiello, Lina Pugliano, Ioanna Laios, Timothy Wilson, Denis Larsimont, Martine J. Piccart-Gebhart, Stefan Michiels, Mark Lackner, Christos Sotiriou, Sherene Loi
Journal: Journal of Clinical Oncology (2013)

11003 Background: ER+/HER2- breast cancers (BCs) constitute the most frequent BC subtype. Their response to endocrine therapy and degree of estrogen dependence are heterogeneous. There is little data available about the genetic changes associated with disease progression in this subtype. This information could facilitate drug development. Methods: A series of 132 ER+/HER2- BC patients diagnosed between 1982 and 2008, with known local-regional (n=10) or distant (n=98) relapse or both (n=24), and available FFPE blocks from their primary (P; n=132) and paired relapse (R; n=49) were identified at a single institution. ER and HER2 status were centrally confirmed. 120 mutations from 11 actionable genes and PTEN protein expression were determined using Fluidigm-based real-time PCR and IHC, respectively. Results: At primary diagnosis, median age was 57 years (27-90); median tumor size 2.5 cm (0.5-11); 75% had positive nodes, 26.5% were pre-menopausal; 80% received adjuvant hormonal treatment. Mutation frequency in P and R samples is presented in the Table. PIK3CA mutations were identified in 44% (58/132) P samples. HRAS, AKT1 and PIK3CA mutations were mutually exclusive. 62.5% (5/8) of KRAS-mutated, 75% (6/8) of MET-mutated, 100% (2/2) of BRAF-mutated and 33.3% (1/3) of FGFR3-mutated P had coexistent PIK3CA mutations. For the 49 evaluated pairs, high concordance for the mutations status was found between P and R. Conclusions: KRAS, BRAF, MET and FGFR3 mutations, found at relatively high frequency in this population of relapsed ER+/HER2- BCs, could represent clinically relevant targets and contribute to mechanisms of recurrence, particularly in PIK3CA-mutated BCs. Mutation profiling of additional paired samples is ongoing and clinical outcome data will be presented. [Table: see text]
Abstract 15641: Genome-Wide Association Study and Meta-Analysis of Aspirin Responsiveness in Individuals of European Descent
Authors: Rehan Qayyum, Haiqing Shen, Nauder Faraday, Lisa R Yanek, Diane M Becker, Rasika Mathias, Braxton D Mitchell, Quince Gibson, William Herzog, Lewis C Becker, Alan R Shuldiner
Journal: Circulation (2011)

While familial studies have established that inter-individual variability in platelet response to aspirin (ASA) is partly due to genetic variation, a genome-wide association study (GWAS) has not be...
Abstract 4290: Risk Factors and Prognostic Implications of Mitral Regurgitation in Severe Aortic Stenosis
Authors: Padmini Varadarajan, Ramdas G Pai
Journal: Circulation (2008)

Introduction: Mitral regurgitation (MR) is present in nearly half of the patients with severe aortic stenosis (AS). Risk factors for its development and its prognostic implications are not clear. Methods: Search of our echocardiographic database between 1993 to 2003 yielded 740 patients with severe AS defined as aortic valve area (AVA) ≤ 0.8cm2. Thorough chart reviews were conducted to collect clinical and pharmacological data. Mortality data was obtained from National death index. Results: Patient characteristics: age 74±13 years; females 60%, EF 54±20%, aortic valve area 0.67±0.17 cm2. MR grade ≥2+ were present in 339 (46%) patients: 2+ in 166 (22%), 3+ in 115 (16%) and 4+ in 58 (8%). There was a progressive decrease in survival with each grade of MR in the whole cohort as well as the surgically and medically treated subsets (p&lt;0.0001, figure ). Presence of 3 and 4+ MR was associated with a larger LV (p&lt;0.0001), lower EF (p&lt;0.0001), greater age (p=0.0001), a smaller aortic valve area (p=0.001) and female gender (p=0.003). It remained an independent predictor of lower survival after adjusting for group differences using the Cox regression model. There was a lower AVR rate in those with 3 or 4+ MR compared to the rest (32 vs. 41%, p=0.03) despite a distinct independent survival advantage with AVR (RR 0.40, p&lt;0.0001). Conclusion: Significant MR is present in nearly half of the patients with severe AS. The risk factors for its development include age, greater AS severity and LV dysfunction. It is an independent predictor of reduced survival.
Health in the AmericasHealth in the Americas
Authors: Jorge Jimenez
Journal: JAMA (2004)

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
Phase III randomized trial of primary chemotherapy with doxorubicin/cyclophosphamide (AC) <b><i>vs</i></b> docetaxel/capecitabine (TX) for stage II/III breast cancer (BC): Interim analysis
Authors: H. G. Lee, J. J. Lee, K.-H. Jung, Y. Kwon, E. H. Shin, K.-W. Chung, K. H. Shin, E.-A. Kim, E. S. Lee, J. Ro
Journal: Journal of Clinical Oncology (2004)

607 Background: Recent data suggested docetaxel (T) when added preoperatively to enhance tumor response following AC, significantly improved pathologic tumor response and clinical outcomes. In metastatic BC, TX resulted in higher RR, TTP and OS compared with T alone. Therefore, a phase III study was designed to compare efficacy and toxicity of AC vs TX as primary chemotherapy for stage II/III BC. Methods: Patients (pts) with stage II/III BC without prior hormonal, chemo-, radiation therapy, or surgery (op) other than biopsy were eligible. Pts must have positive axillary LN by PET or sono guided diagnosis, adequate organ and hematologic profiles and good PS (ECOG 0/1). Randomization to receive preoperative AC x 4 (A 60mg/m2 i.v. d1/C 600 mg/m2 i.v. d1 q 3 wk) vs TX x 4 (T 75 mg/m2 i.v. d1/X 1,000mg/m2 p.o. BID d1–14 q 3 wk) was based on stage, ER status, and age. Postoperatively, therapy crosses over to the other arm. Further radiation ± tamoxifen is given. Assessment for clinical response was assisted by 3 serial sono results at baseline, after 2nd and 4th cycles. Results: Total 78 pts were enrolled from 8/02 to 11/03. Age (range 21–66yrs), stage II (56%), ER (54%), HER2 3+ (28%) were well balanced in 2 arms. Thus far, 32 pts in AC /33 in TX completed op. Clinically, 1 CR, 23 PR, 1 MR, 4 SD, 3 PD in AC arm vs 1 CR, 28 PR, 3 MR, 1 SD, 0 PD in TX arm were observed (p=0.03). pCR of primary tumor was 6.3%, AC vs 15.2%, TX (p=0.43), and in LN, 29% vs 27%. Relative dose intensity (%) were 97/96 in AC vs 95/90 in TX. Severe adverse events were G3/4 neutropenia (94 vs 77%), G3 vomiting (3% in AC) and G3 diarrhea, desquamation, hand-foot syndrome (3%, 5%, 8% in TX). 56.2% of pts in AC and 63.6% in TX underwent breast conserving op. Conclusions: Primary therapy with TX resulted in higher clinical response and pCR compared with AC in stage II/III BC at this interim analysis. Active accrual will continue and further updates will be presented. Supported by NCC grant-0210150, Aventis Pharma and Roche Korea. No significant financial relationships to disclose.
P1307 : Inhibition of Pannexin1 channels alleviates acetaminophen-induced hepatotoxicity in mouse
Authors: M. Maes, T.C. Da Silva, I.V.A. Pereira, J. Willebrords, S.C. Yanguas, S. Penuela, H. Jaeschke, B. Cogliati, M. Vinken
Journal: Journal of Hepatology (2015)
SCHIZOPHRENIA; A NEUROBIOLOGIC APPROACH
Authors: Arthur O. Hecker
Journal: Annals of Internal Medicine (1941)

Article1 October 1941SCHIZOPHRENIA; A NEUROBIOLOGIC APPROACHARTHUR O. HECKER, F.A.C.P.ARTHUR O. HECKER, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-15-4-678 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe approach to an understanding of the mechanisms responsible for mental illness has definitely entered a new phase, one characterized by attempted synthesis of data acquired through distinctly separate methods of investigation. This is basically a neurobiological methodology which utilizes data ascertained by the various individual methodologies which are applied to the study of the development, form, and function of the nervous system. This approach attempts to bring psychological studies with their multitudinous ramifications to a physiological level; i.e., it is an effort toward the interpretation of psychological data in the terms of neuronic development and function. It attempts, by...Bibliography1. TREDGOLD AF: Mental deficiency, 5th Ed., 1929, Wm. Wood & Co., Baltimore, Md. CrossrefGoogle Scholar2. RIBBLE MA: Clinical studies of instinctive reactions in new born babies, Am. Jr. Psychiat., 1938, xcv, 149-160. CrossrefGoogle Scholar3. BOLTON J: A contribution to the localization of cerebral function, Brain, 1910, xxxiii, 26. CrossrefGoogle Scholar4. KARLINKENNEDY IWL: Delay in the development of speech, Am. Jr. Dis. Child., 1936, li, 1138-1149. Google Scholar5. LEVIN M: Misunderstanding of the pathogenesis of schizophrenia, arising from the concept of "splitting," Am. Jr. Psychiat., 1938, xciv, 877-889. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Indianhead Gap, Pennsylvania*Received for publication November 30, 1939. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySchizophrenia 1 October 1941Volume 15, Issue 4Page: 678-699KeywordsNervous systemSchizophrenia ePublished: 1 December 2008 Issue Published: 1 October 1941 PDF downloadLoading ...
CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells
Authors: Shujing Liang, Chao Li, Chunlei Zhang, Yunsheng Chen, Liang Xu, Chenchen Bao, Xiaoyong Wang, Gang Liu, Fengchun Zhang, Daxiang Cui
Journal: Theranostics (2015)

Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies.Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands.It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm 2 , 5 min) in vitro experiment.Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established.Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed.Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice.The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.
Sunitinib in metastatic renal cell carcinoma (mRCC): Preliminary assessment of toxicity in an expanded access trial with subpopulation analysis
Authors: M. E. Gore, C. Porta, S. Oudard, G. Bjarnason, D. Castellano, C. Szczylik, P. N. Mainwaring, P. Schöffski, B. I. Rini, R. M. Bukowski
Journal: Journal of Clinical Oncology (2007)

5010 Background: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs, approved multinationally for advanced RCC. The primary aim of this international, open-label trial was to provide sunitinib to mRCC pts who failed =1 prior systemic therapy and were ineligible for other sunitinib trials or had no access to sunitinib before regulatory approval in their country. Methods: Eligibility criteria were minimized to broaden the enrolment population. Pts who were 18 yrs of age or older with histologically-confirmed mRCC received oral sunitinib 50 mg/day in 6-wk cycles (4 wks on Tx, 2 wks off). Physical exam, safety and concomitant meds were assessed every 4 wks. Results: As of Sept 1, 2006, 4,000 pts were enrolled from 181 sites in 36 countries; 2,158 pts (median age, 59 [19- 85]; male/female, 74%/26%) were included in this analysis. Baseline demographics included 106 pts (5%) with non-clear cell histology; 173 pts (8%) with brain mets; 158 pts (7%) with prior antiangiogenic Tx; and 288 pts (13%) with ECOG PS =2. Median Tx duration was 128 days (range 1- 2444) with interruptions in 17% of pts and dose reductions in 30%; 672 pts (31%) discontinued, of which 80 pts (12%) discontinued due to AEs. The median Tx duration was similar to the overall population regardless of age or site of metastatic disease at baseline (brain, bone, lung, liver, lymph nodes or other), but was longer in pts with ECOG PS 0/1 (154 days, range 1–2,444) than with ECOG PS =2 (83 days, range 1–449). The most common treatment-related AEs were diarrhea (39% any grade, 3% grade 3/4), fatigue (35%, 7%) and nausea (33%, 2%), the incidences of which were similar in pts regardless of age or site of baseline metastatic disease; overall, they occurred more frequently in pts with ECOG PS 0/1 vs. ECOG PS =2 (42% vs. 21%, 38% vs. 23%; and 34% vs. 25%, respectively), but differences in grade 3/4 severity were not observed. Median overall survival has not been reached; 19% of pts have died, the lowest incidence among pts with ECOG PS 0/1 (15%) and highest in pts with ECOG PS =2 (43%) and brain mets (34%). Conclusions: Preliminary observations suggest that sunitinib is associated with acceptable tolerability in an expanded access trial regardless of age or site of baseline metastatic disease. [Table: see text]
Pulse-Wave Velocity and Cardiovascular Risk Factors in the Beaver Dam Offspring Study (BOSS) Population
Authors: Wenjun Zhong, Karen J. Cruickshanks, Carla Schubert, F. Javier Nieto, James S. Pankow, Charles W. Acher, Clint T. Baldwin, Guan-Hua Huang, Barbara E. Klein, Ronald Klein, Michael B. Miller, Ted Tweed
Journal: Circulation (2009)
STUDIES ON RED CELL DIAMETER
Authors: J. R. Bell, F. K. Thomas, J. H. Means
Journal: Journal of Clinical Investigation (1926)

During a visit to Guy's Hospital in the summer of 1924 one of us (J.H. M.) became interested in Hurst's (1) use of Price-Jones' method (2) of measuring the diameter of the red cells of the blood in cases of pernicious anemia, and was impressed not only with the possible importance of this procedure as a means of differentiating clinical types of anemia, but also with its possibilities as a method of investi- gating many problems in hematology.Accordingly measurements of this kind were promptly started at the Massachusetts General Hospital and have been in progress ever since.At the present time we are ready to report on a series of 20 normal persons and one of 25 cases of permicious anemia.METHOD
Reduced schedule of antenatal visits
Authors: T. O'Connell
Journal: BMJ (1996)

sample size would have given us 99.9% power to detect a difference in the rate of change in the scores obtained in the paired associate learning test of ¢ 0.1 point a year between treatments.Although it is desirable to test multiple cognitive domains, there are practical limits to what can be achieved in an investigation that has been piggybacked on to a trial with its own demanding protocol.Expediency is necessary to retain the cooperation of the investigators and subjects in this important collaboration.Nevertheless, not all of C D Irvine and S H Irvine's criticisms of our outcome measures are justified.Their contentions that the paired associate learning test may not be a valid measure of intellectual function in late life and that it lacks internal consistency are not supported by the reference that they cite.In research in older populations the validity ofthe test is established as an indicator of decline on the abbreviated mental test score,' as a correlate of cognitive and functional decline as measured by the psychogeriatric assessment