tbuckley/cabot-search huggingface dataset:
Merits of Embryo Screening Debated
Authors: Brian Vastag
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
Metformin as Initial Oral Therapy in Type 2 Diabetes
Authors: Rachel J. Stern, Elizabeth J. Murphy
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Scleroderma
Authors: Jouni Uitto, Eugene A. Bauer, Arthur Z. Eisen
Journal: Journal of Clinical Investigation (1979)

To assess potential abnormalities in collagen metabolism in systemic scleroderma, skin fibroblast lines from patients with this disease were established and compared to control cell lines derived from healthy subjects. For studies on the biosynthesis of procollagen, the cells were incubated with [14C]proline in a medium supplemented with ascorbic acid and β-aminopropionitrile, and the synthesis of nondialyzable [14C]hydroxyproline, in relation to DNA or cell protein, was taken as an index of procollagen formation. Five of eight scleroderma fibroblast cell lines demonstrated procollagen biosynthesis rates significantly higher than the controls, and the mean rate of procollagen synthesis by scleroderma fibroblasts was about twice that of the control cells. Control experiments demonstrated that the specific activity of the intracellular free proline was not different in scleroderma and control fibroblasts, and the mean population doubling times of the scleroderma and the control fibroblast cell lines were the same. The relative synthesis of the genetically distinct procollagens was examined by isolating type I and type III procollagens from the cell culture medium using DEAE-cellulose chromatography. The ratios of type I/III procollagens in scleroderma cell lines did not differ from the controls. The helical stability of the collagenous portion of type I and type III procollagens, estimated by the resistance of 14C-collagen to limited proteolytic digestion with pepsin under nondenaturing conditions, was the same in both scleroderma and control cultures. The capacity of the cells to synthesize enzymatically active and immunologically reacting collagenase was also studied; no marked differences in these parameters could be observed. The results suggest that cultured skin fibroblasts from patients with scleroderma demonstrate a metabolic abnormality expressed as increased synthesis of type I and type III procollagens in a normal ratio. This abnormality may play a role in the excessive accumulation of collagen in the skin and other organs affected in scleroderma.
Abstract 13508: Obesity Phenotype and the Risk of Hypertension and Type 2 Diabetes: Does Cardiorespiratory Fitness Matter?
Authors: Sae Young Jae, Mercedes Carnethon, Won Hah Park, Bo Fernhall
Journal: Circulation (2014)

There is conflicting evidence regarding the association between metabolically healthy obese (MHO) and metabolically unhealthy normal weight (MUNW) with incident hypertension and type 2 diabetes. The role of cardiorespiratory fitness on these associations has not been fully explored. We tested the hypothesis that obesity phenotypes predict incident hypertension and type 2 diabetes, but cardiorespiratory fitness modifies these associations in a prospective study of apparently healthy men. 3800 men (mean age 48±6 yrs, range 20-76 yrs) participated in two health examinations during 1998-2009. All subjects were free of hypertension and type 2 diabetes at baseline examination. MHO was defined as obesity (body mass index ≥ 25 kg/m2) with no more than one metabolic abnormality, and MUNW was defined as body mass index &lt; 23 kg/m2) with two or more abnormalities. Cardiorespiratory fitness was directly measured by peak oxygen uptake during a treadmill test. Incident hypertension and type 2 diabetes were defined as blood pressure ≥140/90mmHg and as ≥6.5% of HbA1c or ≥126mg/dl of fasting glucose at second examination, respectively. During an average follow-up of 5 years (1-12 yrs), there were 371 (9.8%) men incident hypertension and 170 (4.5%) men incident type 2 diabetes. MHO and MUNW were present in 844 (22%) and 249 (6.6%) men. Compared with metabolically healthy normal weight men, MHO and MUNW men were at increased risk for hypertension (relative risk (RR) =1.82, 95% Confidence Interval (CI): 1.29-2.56 and 1.75, 1.11-2.74) and type 2 diabetes (RR=3.68, 1.92-7.07 and 5.35, 2.61-10.94), respectively. These risks in MHO and MUNW men were still persisted with adjustment for confounder variables and cardiorespiratory fitness (hypertension=1.57, 1.05-2.34 and 1.59, 1.01-2.51; type 2 diabetes=3.35, 1.63-6.89 and 4.76, 2.32-9.77). Metabolically healthy obese or metabolically unhealthy normal weight men were at increased risk of hypertension and type 2 diabetes compared with metabolically healthy normal weight men. However, these associations were not attenuated by cardiorespiratory fitness or other confounder factors.
A NOVEL MODEL OF HEPATIC PROGENITOR CELL ACTIVATION USING HEPATOCYTE SPECIFIC MDM2 DELETION DEMONSTRATES COMPLETE PARENCHYMAL REGENERATION FROM PROGENITOR CELLS IN A TWEAK/FN14 DEPENDENT MANNER
Authors: Tom G. Bird, Alicia Cole, Trevor Hay, Luke G. Boulter, John P. Iredale, Alan R. Clarke, Owen J. Sansom, Stuart J. Forbes
Journal: Hepatology (2010)
Abstract P072: Short Sleep Duration is Associated with Elevated Homocysteine Levels
Authors: Megan E Petrov, Michael A Grandner, Carol M Baldwin, Matthew P Buman, Shawn D Youngstedt
Journal: Circulation (2015)

Introduction: Short and long sleep durations are associated with heightened risk for cardiovascular disease and vascular risk factors. Elevated homocysteine is also associated with greater risk for cardiovascular disease; however, studies have yet to investigate the relationship between sleep duration and homocysteine. Hypothesis: We hypothesized that short and long sleep duration would be associated with clinical levels of homocysteine. Methods: Adults (n=2,469; ≥20y) from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) were assessed for habitual sleep duration (coded as &lt;5, 5, 6, 7, 8, 9, and ≥10hrs) and fasting plasma homocysteine levels (&lt;10 [normative], 10 to &lt;15 [pre-clinical] and ≥15 [clinical] μmol/L). Participants were excluded if pregnant, lactating, missing data on the primary variables, or if they had a history of cardiovascular disease, cancer, diabetes, kidney disease, or diagnosed sleep disorder. Population weighted, multinomial logistic regression analyses assessed the relationship between sleep duration and homocysteine after adjustment for age, sex, race/ethnicity, marital and menopausal status, shift work, dietary folate, alcohol intake, cotinine levels, reported physical activity, hypertension, and reported frequency of cessation of breathing at night. Results: Pre-clinical and clinical levels of homocysteine were present in 13.7% and 2.5% of the sample, respectively. The mean sleep duration was 6.9 ± 1.4 hours. In adjusted analyses, sleep duration was significantly related to homocysteine ( p &lt; 0.001). See Table. Very short sleepers (&lt;5hrs) were more likely to have clinical levels of homocysteine (OR: 3.01, 95%CI: 1.38, 6.57) compared to 7-hr sleepers. Conclusions: In a U.S. representative sample of adults without cardiovascular disease or other major conditions, short sleepers were at greater odds for clinical levels of homocysteine Findings suggest that homocysteine may be one mechanism linking short sleep duration to cardiovascular disease.
Increased sensitization of Multiple Myeloma cells to bortezomib (PS341) via pretreatment with cytokines: a genomic analysis.
Authors: Geraline Cow, Gerrard Teoh, Charles Gullo
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3217 

Multiple myeloma (MM), a plasma cell disorder is currently incurable in most patients and accounts for 13% (white populations) to 33% (black population) of all hematological disorders. Although substantial advances have been made in the understanding of the biology of the disease, long-term curative treatments for this disease are still lacking. A major advance in the disease treatment of MM was the discovery and use of PS-341 (bortezomib, a proteasome inhibitor) in patients with refractory MM. This boronic acid dipeptide, is known to inhibit the activation of NF-κB and thus disrupts the production of downstream pro-MM survival molecules such as IL-6, VEGF, and adhesion proteins and directly induces apoptosis. Furthermore, a number of studies have indicated that this inhibitor also sensitizes MM cells to the apoptotic effect of alkylating agents and DNA-damaging agents. Due to the reported addiction of MM to the NFκB-induced survival pathways and the direct effects of CD40 on the proliferation of MM cells, we asked if CD40-stimulation using soluble recombinant CD40L could sensitize MM to the effects of PS-341. Here we show that CD40L strongly sensitizes RPMI and SGH-MM5 cells to the effects of the proteasome inhibitor by reducing the IC50 of the drug in the presence of the cytokine as compared to the drug alone. This was observed in trypan blue viability and proliferation assays in cells treated with PS-341 alone or in combination with sol-CD40L. After 12 hours, the effect of the cytokine sensitization was stronger (25-fold sensitization in SGH-MM5 and 8 fold for RPMI) and had less of an effect at 24 hours with a 2 to 5-fold sensitization for both MM cell lines. Furthermore, analysis of the DNA content of the population of cells using propidium iodide and flow cytometric analysis revealed a strong shift in the cells from G1 phase of the cell cycle to the Sub G0 phase within six to 12 hours of treatment with PS-341 which was unchanged with the addition of CD40 stimulation, suggesting that CD40L does not contribute to death itself but enhances the effects of PS-341-induced cell cycle arrest. We next stimulated our SGH-MM5 cell lines with sCD40L, PS-341, or both sCD40L plus PS-341 for 6 hours. RNA was then extracted and subjected to U133A plus Affymetrix gene chip analysis. Each treatment group was compared using multi-variance ANOVA statistical methods. Gene signatures revealed significant differences between the three conditions and transcriptional differences between the various treatment groups are discussed.
Advice for Aspiring Volunteer Physicians
Authors: M Mitka
Journal: JAMA (1999)

BEFORE PACKING ONE’S BAGS AND flying off to some exotic locale to do medical mission work, a physician should address a variety of factors to ensure a worthwhile experience. First of all, rarely do physicians volunteer services abroad without working through a sponsoring organization. A physician should try to join with a group that offers the type of experience he or she wants. For example, some organizations send teams of physicians, with their own equipment and support staff, to treat a specific population. Others send physicians by themselves with the idea of teaching local practitioners through observation and example. Still others send physicians to areas where emergency relief is needed, such as in war-torn countries or those devastated by natural disasters. The following directory of organizations includes some of each sort; those contemplating volunteering should ask the group of interest for details. This is the sixth such directory to be published in JAMA; the last appeared 3 years ago (JAMA. 1996;276:355-359). Any group that wishes to be listed in the future may send the relevant information to JAMA’s Medical News section.
Abstract 916: A multidimensional analysis of predictive biomarkers in colorectal cancer
Authors: Marisa Mariani, Shiquan He, Mark McHugh, Mirko Andreoli, Deep Pandya, Steven Sieber, Zheyang Wu, Paul Fiedler, Shohreh Shahabi, Cristiano Ferlini
Journal: Cancer Research (2014)

Abstract Background: CRC cancer is one of the deadliest diseases in Western countries. In order to develop predictive biomarkers for CRC (colorectal cancer) aggressiveness, we analyzed retrospectively 267 CRC patients via a novel, multidimensional biomarker platform. Methods: Using nanofluidic technology for qPCR analysis and quantitative fluorescent immunohistochemistry for protein analysis, we assessed 33 microRNAs, 124 mRNAs and 9 protein antigens. Analysis was conducted in each single dimension (microRNA, gene or protein) using both the multivariate Cox model and Kaplan-Meier method. Thereafter, we simplified the censored survival data into binary response data (aggressive vs. non aggressive cancer). Subsequently, we combined the data into multidimensional scores using inverse sliced regression for sufficient dimension reduction. Accuracy was assessed using the Area under the Curve (AUC) and the receiver operating characteristic (ROC) method. Results: Single dimension analysis led to the discovery of individual factors that were significant predictors of outcome. These included seven specific microRNAs, four genes, and one protein. When these factors were quantified individually as predictors of aggressive disease, the highest demonstrable area under the curve (AUC) was 0.68. By contrast, when all results from single dimensions were combined into multidimensional biomarkers, AUCs were dramatically increased with values approaching and even exceeding 0.9. Conclusions: Single dimension analysis generates statistically significant predictors, but their predictive strengths are suboptimal for clinical utility. A novel, multidimensional approach overcomes these deficiencies. Newly derived multidimensional biomarkers have the potential to meaningfully guide the selection of therapeutic agents for individual patients while elucidating molecular mechanisms driving disease progression. Citation Format: Marisa Mariani, Shiquan He, Mark McHugh, Mirko Andreoli, Deep Pandya, Steven Sieber, Zheyang Wu, Paul Fiedler, Shohreh Shahabi, Cristiano Ferlini. A multidimensional analysis of predictive biomarkers in colorectal 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 916. doi:10.1158/1538-7445.AM2014-916
Abstract 17474: Management State of Low-Density Lipoprotein Cholesterol has a Favorable Effect on Left Ventricular Reverse Remodeling in Patients With ST-Segment Elevation Acute Myocardial Infarction
Authors: Akihiro Makino, Atsuhiko Matsunaga, Minako Yamaoka-Tojo, Ryo Kameda, Takashi Masuda, Junya Ako
Journal: Circulation (2014)

Left ventricular remodeling following ST elevation acute myocardial infarction (STEMI) is still an issue in the primary percutaneous coronary intervention (PCI) era. This study aimed to examine whether control of cholesterol levels is predictive of reverse remodeling in patients with STEMI. Subjects were 56 patients with first STEMI successfully and completely reperfused. Single photon emission computed tomography (SPECT) was used to measure LV function at 1 and 6 months after onset. Reverse remodeling was defined as a &gt;10% reduction in LV end-systolic volume at 6-month follow-up compared with baseline SPECT. Patients were divided into reverse remodeling (n=15) and non-reverse remodeling (n=41) groups, and clinical characteristics including age, sex, body mass index, peak serum creatine kinase, number of coronary artery lesions, coronary risk factors and medications, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio, and triglycerides were compared between the groups. We examined the proportions of patients with target LDL-C (&lt;70 mg/dL), HDL-C (≥40 mg/dL), and TG (&lt;150 mg/dL) levels, and LDL-C/HDL-C ratio of &lt;1.5. Multivariate stepwise logistic regression analyses were performed to evaluate the relationship between occurrence of reverse remodeling and clinical characteristics. In baseline clinical characteristics, there were significant differences between the two groups regarding to management states of LDL-C levels and the LDL/HDL ratio. The proportions of patients achieving target LDL-C levels and LDL-C/HDL-C ratio were higher in the reverse remodeling group than in the non-reverse remodeling group (80% and 17%, p&lt;0.0001; 60% and 10%, p&lt;0.0001, respectively). Logistic regression analysis revealed that patients with target LDL-C levels were significantly more likely to show reverse remodeling (odds ratio 19.429, 95% confidence interval 4.317-87.432, p&lt;0.0001). The present study showed that the good control of LDL-C independently predicts reverse remodeling in patients with first STEMI. This finding underscores the need for achieving and maintaining target LDL-C levels through secondary prevention for reverse remodeling.
J. Harold Cheek, M.D
Authors: S. Stockwell
Journal: CA A Cancer Journal for Clinicians (1983)

Dr. Cheek's article and view stimulated further research in the field.Today, 30 years after the publication of Dr. Cheek's survey, the emphasis is on prompt histo logic diagnosis and treatment of any mass in the breast of a pregnant or lactating womanâ€"essentially ignoring the preg nancy and accepting a small risk of spon taneous abortion.
Abstract 78: A novel orthotopic mammary epithelial cell (MEC) transplantation model of breast cancer formation
Authors: Zoltan Szucs, Michael D. Prater, John Stingl, Kevin M. Brindle
Journal: Cancer Research (2014)

Abstract The pathogenesis of breast cancer is polygenic. Exploring the involvement of different onco- and tumor suppressor genes, and combinations of these genes, in early breast cancer formation is important for understanding the natural history of the disease. Preclinical studies of the fundamental biological and metabolic changes that occur during breast oncogenesis in currently available transgenic mouse models are limited by the requirement for tissue-specific promoters and the random nature of tumor formation. The mouse mammary gland is a unique organ in that most of its development occurs after birth. Moreover, isolated mammary epithelial cells (MECs) have the capacity to regenerate a functional gland upon orthotopic transplantation into the cleared fat pad of a syngeneic recipient. We describe here a new transplantation system using pure MECs derived from genetically engineered mice harboring floxed oncogenes. First we selected in vitro for a stromal and hematopoietic cell-free MEC preparation. In the MEC donor transgenic strains the activation of oncogenes (K-Ras, c-Myc) or the deletion of tumor suppressors (p53) is dependent on Cre recombinase expression (Cre-lox system). Using an adenoviral Cre-recombinase vector we activated these oncogenic changes in isolated MECs. Colony formation assays demonstrated the viability of these mixed transduced/non-transduced MEC populations. Following transplantation into the cleared fat pad of syngeneic mice the transduced MECs preserved their fat pad repopulating and duct forming potential and the induced oncogenic changes resulted in mammary tumor formation. This proposed system offers tissue specific promoter-free and lactation independent spatial control of oncogenic events in the epithelial cell compartment of breast ducts. Citation Format: Zoltan Szucs, Michael D. Prater, John Stingl, Kevin M. Brindle. A novel orthotopic mammary epithelial cell (MEC) transplantation model of breast cancer formation. [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 78. doi:10.1158/1538-7445.AM2014-78
Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness
Authors: Fiona E. Karet, Karin E. Finberg, Raoul D. Nelson, Ahmet Nayir, Hilal Mocan, Sami A. Sanjad, Juan Rodriguez-Soriano, Fernando Santos, Cor W.R.J. Cremers, Antonio Di Pietro, Barry I. Hoffbrand, Jacek Winiarski, Aysin Bakkaloglu, Seza Ozen, Ruhan Dusunsel, Paul Goodyer, Sally A. Hulton, Doris K. Wu, Anne B. Skvorak, Cynthia C. Morton, Michael J. Cunningham, Vivekanand Jha, Richard P. Lifton
Journal: Nature Genetics (1999)
Results of Clinical Trials Sponsored by For-Profit vs Nonprofit EntitiesResults of Clinical Trials Sponsored by For-Profit vs Nonprofit Entities
Authors: Jonathan B. Rosefsky
Journal: JAMA (2003)

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