tbuckley/cabot-search huggingface dataset:
Sequencing of the Malaria Genome Opens Door to Vaccines and New Drugs
Authors: Joan Stephenson
Journal: JAMA (2002)

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
Abstract 1717: Downregulation of miR-217 correlates with resistance of ph+ leukemia cells to ABL tyrosine kinase inhibitors
Authors: Takayuki Ikezoe, Chie Nishioka, Jing Yang, Akihito Yokoyama
Journal: Cancer Research (2014)

Abstract This study found that long-term exposure of chronic myelogenous leukemia (CML) K562 cells to BCR/ABL thyrosine kinase inhibirors (TKIs) caused drug-resistance in association with an increase in levels of DNA methyltransferases (DNMTs) and a decrease in levels of microRNAs (miRNAs) miR-217. These observations are clinically relevant; an increase in levels of DNMT3A in association with downregulation of miR-217 were noted in leukemia cells isolated from individuals with BCR/ABL TKI-resistant philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) and CML. Further studies with TKI-resistant K562 cells found that forced expression of miR-217 inhibited expression of DNMT3A through a miR-217-binding site within the 3′-untranslated region of DNMT3A and sensitized these cells to growth inhibition mediated by the TKI. Of note, long-term exposure of K562 cells to dasatinib (10 nM) together with 5-Aza-2′-deoxycytidine (5-AzadC) (0.1 μM) potently inhibited proliferation of these cells in association with upregulation of miR-217 and downregulation of DNMT3A in vitro. In addition, a decrease in levels of DNMT3A and an increase in levels of miR-217 were noted in K562 tumors growing in immune deficient mice that were treated by the combination of 5-AzadC and dasatinib. Taken together, Ph+ leukemia cells acquire TKI-resistance via downregulation of miR-217 and upregulation of DNMT3A. Inhibition of DNMT3A by forced expression of miR-217 or 5-AzadC may be useful to prevent drug resistance in individuals who receive TKIs. Citation Format: Takayuki Ikezoe, Chie Nishioka, Jing Yang, Akihito Yokoyama. Downregulation of miR-217 correlates with resistance of ph+ leukemia cells to ABL tyrosine kinase inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1717. doi:10.1158/1538-7445.AM2014-1717
Patients' Genes May Influence Quality of Life After Cancer Chemotherapy
Authors: Tracy Hampton
Journal: JAMA (2004)

tentiate the antiproliferative effects of tamoxifen in both estrogen-dependent and estrogen-independent breast cancer cells in culture. Using this as a rationale, Nesaretnam and colleagues have begun a clinical trial in Kuala Lumpur to look at the effects of tocotrienols in combination with tamoxifen in 240 women with stage 1 or 2 estrogen-dependent breast cancer. The end points will be recurrence of disease and metastasis. Using microarray technology to study the specific genes regulated in breast cancer cells by tocotrienols, Nesaretnam’s group has identified a few genes involved in inhibiting cell growth and differentiation. These results suggest that tocotrienols affect cell homeostasis independently of their antioxidant activity, she said.
Abstract 4003: Clinical and biological significance of CXCR6 in lung cancer
Authors: Hina Mir, Pranav Gupta, Rajesh Singh, Praveen K. Sharma, Gurpreet Kaur, Ashley B. Ward, William E. Grizzle, James W. Lillard, Shailesh Singh
Journal: Cancer Research (2014)

Abstract Lung cancer is the leading cause of cancer related deaths worldwide in both men and women. Metastasis is responsible for most lung cancer related deaths; therefore, a better understanding of the metastatic processes and therapies designed to prevent the spread of cancer cells are greatly needed. The specific mechanisms that promote metastases have not been fully elucidated. Among all known chemokine receptors involved in cancer progression, most cancer cells including lung cancer express CXCR4. Furthermore, involvement of CXCR4 and CCR7 in breast cancer and CXCR4, CCR9 and CX3CR1 in prostate cancer progression further indicates that multiple chemokine receptors are involved in dictating the multi-step process of metastasis. In this study, we show significantly higher expression of CXCR6 and CXCL16 in lung cancer tissues compared to normal matched tissues. Expression of CXCR6 was significantly higher in adeno- carcinoma compared to squamous cell carcinoma. It addition to these, serum levels of CXCL16, the only natural ligand for CXCR6, was also significantly higher in lung cancer patients compared to normal healthy donor. Furthermore, serum CXCL16 was also significantly higher in patients with adenocarcinoma compared to patients with squamous cell carcinoma. Impact of this chemokines-receptor axis was determined in lung cancer cell lines in vitro, which express CXCR6 and CXCL16. Like tissues, lung cancer cells showed higher expression of CXCR6 and CXCL16 compared to normal lung epithelial cells (NuLi-1). Interestingly, expression of CXCR6 was highest in cell lines derived form adenocarcinoma followed by cell lines from squamous cell carcinoma. Furthermore, we demonstrate that CXCR6 and soluble CXCL16 interaction plays a crucial role in lung cancer cells migration and invasion. The mechanism underlying these clinically and biologically important findings need to be further explored. Increased serum CXCL16 in lung cancer patients with metastatic disease required further validation as a potential therapeutic target and/or diagnostic marker for lung cancer. Citation Format: Hina Mir, Pranav Gupta, Rajesh Singh, Praveen K. Sharma, Gurpreet Kaur, Ashley B. Ward, William E. Grizzle, James W. Lillard, Shailesh Singh. Clinical and biological significance of CXCR6 in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4003. doi:10.1158/1538-7445.AM2014-4003
Abstract 3436: Ameloblastoma driver mutations revealed by next-generation sequencing of formalin-fixed paraffin-embedded specimens
Authors: Andrew C. McClary, Robert T. Sweeney, Jewison Biscocho, Benjamin R. Myers, Lila Neahring, Kevin A. Kwei, Kunbin Qu, Xue Gong, Tony Ng, Carol D. Jones, Sushama Varma, Justin I. Odegaard, Brian Rubin, Megan L. Troxell, Robert J. Pelham, James L. Zehnder, Philip A. Beachy, Jonathan R. Pollack, Robert B. West
Journal: Cancer Research (2014)

Abstract Rare cancer types are not only understudied, but are typically represented by formalin-fixed paraffin-embedded (FFPE) (rather than freshly-frozen) specimens that are suboptimal for genomic analysis. Ameloblastoma is one such rare tumor type, thought to arise from ameloblasts, the cells that deposit enamel during tooth development. Though typically benign, ameloblastomas are locally destructive to the jaw and face, and new non-surgical interventions are needed. To discover novel driver mutations and therapeutic targets, we optimized methods and performed whole-transcriptome sequencing and/or targeted exon sequencing (TruSeq Cancer Panel) of 8 FFPE cases. Identified mutations were verified, and then evaluated on a larger, independent set of 21 FFPE cases by PCR and Sanger sequencing. From the analysis, we identified recurrent somatic mutations in three key developmental or signaling pathways, including Hedgehog, fibroblast growth factor, and MAP kinase pathways. Functional interrogation of a novel Hedgehog pathway mutation confirmed increased basal pathway activity, and defined the response profile to various pharmacologic Hedgehog inhibitors. Together, our results define new ameloblastoma drivers and nominate new molecularly-directed therapies for this rare but disfiguring disease. More generally, our findings validate a robust approach for discovering driver mutations in rare cancers. Citation Format: Andrew C. McClary, Robert T. Sweeney, Jewison Biscocho, Benjamin R. Myers, Lila Neahring, Kevin A. Kwei, Kunbin Qu, Xue Gong, Tony Ng, Carol D. Jones, Sushama Varma, Justin I. Odegaard, Brian Rubin, Megan L. Troxell, Robert J. Pelham, James L. Zehnder, Philip A. Beachy, Jonathan R. Pollack, Robert B. West. Ameloblastoma driver mutations revealed by next-generation sequencing of formalin-fixed paraffin-embedded specimens. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3436. doi:10.1158/1538-7445.AM2014-3436
Abstract 19660: Time-resolved Wall Stress Assessments Reveal Marked Late Systolic Load in Heart Failure with Reduced Ejection Fraction (HFREF)
Authors: Julio A Chirinos, Prasad Konda, Anjaneyulu Dunde, Deepa Rawath, Payman Zamani, Neetha Vadde, Vandan Panchal, Prithvi Shiva-Kumar, Victor Ferrari, Patrick Segers, Scott Akers
Journal: Circulation (2014)

Background: Systolic myocardial wall stress (MWS) quantifies myocardial afterload. MWS has historically been assessed only in end-systole, but recent time-resolved assessments in subjects with normal LV EF demonstrate that peak stress occurs in early systole, followed by a marked shift in the pressure-stress relation that reduces late systolic stress in normal hearts. This shift is dependent on progressive geometric changes during ejection.

Hypothesis: HFREF is associated with an abnormal time course of LV MWS.

Methods: We compared 18 subjects with HFREF (mean age=56; mean BMI=30 kg/m2; mean LV EF=34%) to controls matched for age, body size and arterial load. We assessed time-resolved LV geometry and central pressure with cardiac MRI and carotid tonometry, respectively. We computed MWS throughout ejection (Arts method).

Results: Peak MWS (736 vs. 735 kdynes/cm2; P =0.99) and mean MWS throughout ejection (633 vs. 580 kdynes/cm2; P =0.38) were not significantly different between the groups. However, subjects with HFREF demonstrated a delay in the time to peak stress (103 msec vs. 79 msec into ejection; P <0.0001). Furthermore, despite similar wave reflection magnitude (0.50 vs. 0.49; P =0.91) and late systolic pressure augmentation between the groups, subjects with HFREF demonstrated a pronounced increase in the ratio of late (second half of ejection) vs. early (first half of ejection) MWS-time integral (0.91 vs. 0.75; P <0.0001), which was due to a markedly blunted mid-systolic shift in the pressure-stress relation (145 vs. 285 kdynes/cm2; P<0.0001), resulting in a failure to reduce late systolic wall stress for any given pressure (Figure).

Conclusions: HFREF is associated with marked abnormalities in the systolic loading sequence due to an intrinsically abnormal pressure-stress relation during ejection. For any given arterial load, this exposes the myocardium to excessive late systolic stress and may promote a vicious circle of adverse LV remodeling and failure.

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A book that changed my practice: School can be hell
Authors: D. Hartman
Journal: BMJ (1998)

I have two children of my own. They are 4 and 7, and they seem to enjoy the social and intellectual stimulation of school. But not all children enjoy school, and many do not feel that they are learning anything useful. This seems to be especially true of secondary schools, which are much less nurturing and less fun than primary schools. When I encounter teenagers who are not going to school, they will often be able to articulate understandable reasons for non-attendance, and the classic label of school phobia does not seem to fit in the way that it does with younger children. There is no irrational fear of an innocuous stimulus. Instead, I hear stories of frightening playgrounds, friends who taunt them, steal their personal possessions, even assault them, lessons that …
Book: The Nazi War on Cancer
Authors: R. Cooter
Journal: BMJ (2000)

Robert N Proctor Princeton University Press, £18.95, pp 390 ISBN 0 691 00196 0 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Is “mad and bad” what springs to mind when you think of Nazi medical science?Is the late 20th century United States where you locate the groundswell of support for natural foods, vocal concerns over ill health and the environment, and campaigns against passive smoking? And is it the famous 1950 study of Doll and Hill that you associate with establishing the link between smoking and cancer? If so, this book is essential reading, but prepare to be shocked. The medical fraternity of the notorious Third Reich emerge here … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Book: Neurology and Medicine
Authors: Y. Hart
Journal: BMJ (2000)

Eds R A C Hughes, G D Perkin BMJ Books, £45, pp 430 ISBN 0 7279 1224 0 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> ![Graphic][4]</img> About 20% of acute medical admissions to district general hospitals are for neurological problems, often in the context of other medical conditions. Their management may be complicated: neurology is one of those subjects in which general physicians often feel least comfortable, and in many parts of the country neurologists remain thin on the ground and may themselves have limited experience … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Abstract 9687: Exercise Improves BMI Z-Score in Overweight and Obese Children and Adolescents: A Systematic Review With Meta-Analysis
Authors: George A Kelley, Kristi S Kelley, Russell R Pate
Journal: Circulation (2014)

Introduction: Previous studies have reached conflicting conclusions regarding the effects of exercise on adiposity in overweight and obese children and adolescents. Hypothesis: Exercise (aerobic, strength, or both) improves body mass index (BMI) z-score in overweight and obese children and adolescents. Methods: Studies meeting the following criteria were included: (1) randomized controlled trials, (2) exercise ≤ 4 weeks, (3) overweight/obese children and adolescents 2-18 years of age, (4) studies published in any language from 1990-2012, (5) BMI z-score data available. Studies were derived from 7 electronic databases, cross-referencing and expert review. Two investigators independently selected and abstracted all data. Exercise minus control group changes were calculated from each study and inverse variance weighted. Results were pooled using a random-effects model with non-overlapping 95% confidence intervals (CI) considered statistically significant. Q and I2 statistics were used to assess heterogeneity...
New Vaccine Should Ease Meningitis Fears
Authors: Mike Mitka
Journal: JAMA (2005)

THE RECENT LICENSING OF A NEW meningococcal conjugate vaccine has prompted government officials to expand recommended immunization practices. The new vaccine is expected to drastically reduce the prevalence of invasive meningococcal disease caused by Neisseria meningitidis serogroups A C Y and W-135 which make up the majority of cases in the United States. The Advisory Committee on Immunization Practices to the Centers for Disease Control and Prevention (CDC) recommended on February 10 that children aged 11 and 12 years teens entering high school and college freshman living in dormitories receive meningococcal (groups A C Y and W-135) polysaccharide diphtheria toxoid conjugate vaccine (Menactra). This vaccine manufactured by Sanofi Pasteur (Swiftwater Pa) received US Food and Drug Administration approval on January 14 2005.  (excerpt)
187. Adeno-Associated Virus Vector-Mediated Soluble Flt-1 Gene Transfer Prevents Diabetic Retinopathy in Spontaneously Diabetic Rat Model
Authors: Junichi Ideno, Hiroaki Mizukami, Akihiro Kakehashi, Yuka Saito, Takashi Okada, Akihiro Kume, Masatoshi Kuroki, Masanobu Kawakami, Shun Ishibashi, Keiya Ozawa
Journal: Molecular Therapy (2004)

Top of pageAbstract
Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus (DM), and is the most common cause of postnatal blindness. Vascular endothelial growth factor (VEGF), a potent endothelial cell-specific mitogen plays a critical role in angiogenesis of DR. Spontaneously-diabetic non-obese Torii (SDT) rat was recently established as one of the best-suited models to study DR, because they spontaneously develop DM and shows DR that is characterized with intraretinal microvascular abnormalities (IRMA) and tractional retinal detachment (ref. 1). In this study, we evaluated the therapeutic potential of gene transfer of the soluble VEGF receptor, sFlt-1, in SDT rat using adeno-associated virus vector serotype 5 encoding human sFlt-1 gene (AAV-sFlt-1). Vectors were injected into the subretinal space of 27-week-old SDT rats using 39-guage nyron needle under a surgical microscope. One eye was designated as the “treated side” that received AAV-sFlt-1 in addition to vectors encoding β-galactosidase gene (AAV-LacZ), whereas the other was “control” that received only AAV-LacZ. All of the SDT rats showed hyperglycemia throughout the study, and HbA1c levels were high at the end of the study (9.4 ± 0.95 %: means ± S.D.). Thirty weeks after vector administration, the progression of DR was assessed by fluorescein angiography (FAG) using three parameters; avascular area, extensive hyperfluorescein and arterial narrowing, without the information of injected vectors. Progression of DR in treated eyes was significantly less than that in the control eyes. X-gal staining of the retinal tissue demonstrated the persistent transgene expression for 30 weeks. Moreover, plasma levels of sFlt-1 were undetectable by ELISA, and no adverse effects of sFlt-1 gene therapy were observed throughout the study. These results indicate that local sFlt-1 gene transfer inhibits IRMA of SDT rat, and offers a powerful therapeutic potential to the management of DR.
Abstract 17736: Cardiomyocyte Specific Loss of Diacylglycerol Acyl Transferase 1 (Dgat1) Reproduces the Abnormalities in Lipids Found in Severe Heart Failure
Authors: Chad M Trent, Li Liu, Xiang Fang, Ni-Huiping Son, Hongfeng Jiang, William S Blaner, Yu-Xin Yin, Robert V Farese, Shunichi Homma, Andrew V Turnbull, Jan W Eriksson, Shi-Lian Hu, Henry N Ginsberg, Li-Shin Huang, Ira J Goldberg
Journal: Circulation (2014)

Diacylglycerol acyl transferase 1 (DGAT1) catalyzes the final step in triglyceride (TG) synthesis, the conversion of diacylglycerol (DAG) to TG. Dgat1-/- mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function we created cardiomyocyte specific DGAT1 knockout (hDgat1-/-) mice. hDgat1-/- mice hearts had 95% increased DAG and 85% increased ceramides compared to floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide (Bnp) increased 5-fold in hDgat1-/- hearts and fractional shortening (FS) was reduced. This was associated with a 30% increase in PPARalpha and a 40% increase in Cd36. We crossed hDgat1-/- mice with previously described enterocyte-specific Dgat1 knockout mice (hiDgat1-/-). This corrected the early mortality, improved FS 40%, and reduced cardiac ceramide and DAG content. Treatment of hDgat1-/- mice with GLP-1 receptor agonist exenatide for 1 week reduced Bnp mRNA by 50%, improved FS, and reduced heart DAG and ceramide content by 30-40%. Increased fatty acid uptake into hDgat1-/- hearts was normalized by exenatide. Reduced activity of protein kinase Cα (PKCα), which is known to be increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.
Abstract P155: The Impact of Drinking Patterns on Differences in the Alcohol-Mortality Relationship between Blacks and Whites in the United States
Authors: Chandra L Jackson, Frank B Hu, Ichiro Kawachi, David R Williams, Kenneth J Mukamal, Eric B Rimm
Journal: Circulation (2014)

Background: Moderate alcohol consumption appears to confer survival benefits, but previous studies suggest that blacks may not experience such benefits due to, for example, differences in genetic polymorphisms in ethanol metabolizing genes or societal/behavioral factors related to type and pattern of consumption. Investigating potential Black-White differences in the alcohol-mortality relationship may also help illuminate if apparent benefits of moderate alcohol consumption are confounded by lifestyle and socioeconomic characteristics. Few studies, however, have included a sufficient number of blacks. Objective: To investigate Black-White differences in the relationship between alcohol consumption and all-cause mortality. Methods: We pooled cross-sectional surveys of nationally representative samples of 145,143 adults in the National Health Interview Survey from 1997-2002 with mortality follow-up through 2006. Usual drinking days/week and level of alcohol consumed/day were based on self-report. Race-sex specific Cox regression analyses were used to adjust for marital status, education, physical activity, smoking status, and other potential confounders. Results: Over 9 years of follow-up, there were 13,366 deaths: 11,221 in whites and 2,145 in blacks. Participants who consumed 1 drink/day on 3-7 days/week had the lowest age-adjusted mortality rates (MR)/1,000 person years among white men (MR: 66.5 [95%CI: 57.7-75.3]) and women (MR: 34.3 [95%CI: 27.1-41.5]). Two drinks/day on ≤2 days/week in black men (MR: 101.9 [95%CI: 69.3-134.5]) and 1 drink/day ≤2 days/week in black women (MR: 60.0 [95%CI: 41.8-78.1]) was associated with the lowest MR. Compared to never drinkers after accounting for important covariates, the lowest relative risk of mortality for white men (HR=0.55 [95%CI: 0.42-0.74]) was found among those who consumed 2 drinks between 3 to 7 days/week, and white women (HR=0.39 [95%CI: 0.26-0.59]) consuming 1 drink/day on 3 to 7 days/week had the lowest mortality risk. Black women (HR=0.44 [95%CI: 0.27-0.72]) consuming 1 drink on ≤2 days/week had the lowest mortality risk, and black men (HR=0.52 [95%CI: 0.26-1.01]) who consumed 2 drinks ≤2 days/week had the lowest risk of total mortality. Conclusions: Light-to-moderate drinking patterns of alcohol consumption were associated with lowest all-cause mortality among white and black men and women although the apparent nadir varied by race and sex. Further research investigating racial differences in drinking patterns and health outcomes is warranted.