tbuckley/cabot-search huggingface dataset:
AN ERROR AND AN APOLOGY
Authors: PETER JAMES DYCK
Journal: Annals of Internal Medicine (1967)

ExcerptTo the Editor:I would like to draw your attention to an editorial change in the book review onPain, which appeared in the March issue, that is incorrect. It concerns the paragraph on p. 630, which reads, "Some of the chapters of the book are inadequate due to their brevity and their inept coverage of the subject, for example, the first chapter by Weddell." My own statement was, "Some of the chapters of the book are inadequate due to their brevity and lack of coverage of the subject, for example, the first chapter by Weddell." I feel embarrassed that...
167. Polyethyleneimines as Vehicles for Oral Gene Delivery
Authors: Eytan A. Klausner, Kam W. Leong
Journal: Molecular Therapy (2006)

Oral gene therapy aims to treat immune-, gastrointestinal- or systemic diseases by ingestion of genetic materials. Compared to the other routes of administration, the oral route is the most convenient, but also the most challenging for gene delivery. Previous studies have shown that oral delivery of chitosan nanoparticles complexed with 0.6 mg DNA encoding FVIII resulted in phenotypic correction of Hemophilia A. The treated animals, unlike control group survived a tail-clipping test. Polyethyleneimines (PEIs) are among the most commonly studied non-viral vectors for in-vivo applications. They have been evaluated in CNS, lung and intratumoral gene transfer studies. However there is no report on PEI as a carrier for oral gene delivery. We have studied the effects of types of PEI, nature of plasmid DNA, and DNA dose on secreted embryonic alkaline phosphatase (SEAP) expression in mice following oral administration of the SEAP gene. SEAP DNA-PEI nanoparticles having a nitrogen to phosphate (N/P) molar ratio of 10 were warmed with unflavored Gelatin Knox™ and cooled to form cubes. Mice (n=10) were fed with 10g of PEI-DNA nanoparticles as gelatin cubes over a period of two days. The different formulations are shown in Table 1. The effect of the formulation on SEAP expression in mice is seen in Fig. 1.Table 1PEI-SEAP DNA nanoparticles formulationsGroupPEI (25 kDa)DNA dose, mgPlasmid type typeABranched1.25CMV promoter-human SEAP, gWiz™SEAP (Gene Therapy Systems, Inc.)BLinear1.25CMV promoter-human SEAP, gWiz™SEAP (Gene Therapy Systems, Inc.)CLinear2.5CMV promoter-human SEAP, gWiz™SEAP (Gene Therapy Systems, Inc.)DBranched1.25No CpG motifs-mouse SEAP, pCpG-mSEAP (Invivogen)ELinear1.25No CpG motifs-mouse SEAP, pCpG-mSEAP (Invivogen)FUntreated animals—— Open table in a new tab The systemic SEAP activity was extremely low in all groups. However, statistically significant activities above background of untreated animals could be observed in the following groups: Formulations A and E on day 2; Formulation C on days 2 and 5; and Formulation D on days 2 and 8. While this study shows that systemic transgene expression can be achieved by oral administration of PEI-DNA nanocomplexes, it also highlights the inefficiency of this delivery system. Work is underway to further optimize the formulation and evaluate other gene carriers.
Excessive Antibiotic Prescribing for Sore Throat and Acute Bronchitis Remains Common
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

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
Fluorocarbon-Polyol Artificial Blood Substitutes
Authors: Philip R. Steinmetz, Christine Balko, Robert P. Geyer
Journal: New England Journal of Medicine (1973)

THERE are many reasons for seeking an artificial whole-blood substitute that can replace both plasma proteins and cells. Perfusion of organs for metabolic studies or transplant purposes would alone make the development of such a product worthwhile. Complete perfusion of living animals with an artificial preparation would afford the opportunity to carry out many investigations not possible when normal blood is present. The eventual formulation of a safe, practical whole-blood substitute would be of possible value in cases in which normal blood might otherwise be used. Interest in complete replacement of the blood of living animals1 rather than the usual . . .
Enhanced Cellular Uptake of Remnant High-Density Lipoprotein Particles
Authors: Changting Xiao, Takehiko Watanabe, Yi Zhang, Bernardo Trigatti, Linda Szeto, Phil W. Connelly, Santica Marcovina, Tomas Vaisar, Jay W. Heinecke, Gary F. Lewis
Journal: Circulation Research (2008)

A low level of high-density lipoprotein (HDL) cholesterol is characteristic of insulin resistance and hypertriglyceridemia and likely contributes to the increased risk of cardiovascular disease associated with these conditions. One pathway involves enhanced clearance of lipolytically modified HDL particles, but the underlying mechanisms remain poorly understood. Here, we examine the effect of triglyceride enrichment and hepatic lipase hydrolysis on HDL binding, internalization, and degradation in cultured liver and kidney cells. Maximal binding of remnant HDL (HDL enriched with triglycerides followed by hepatic lipase hydrolysis), but not binding affinity, was markedly higher than native and triglyceride-rich HDL in both HepG2 cells and HEK293 cells. Compared with native and triglyceride-rich HDL, remnant HDL was internalized to a greater extent in both cell types and was more readily degraded in HEK293 cells. The increased binding of remnant HDL was not mediated by the low-density lipoprotein receptor or scavenger receptor class B type I (SR-BI), because enhanced remnant HDL binding was observed in low-density lipoprotein receptor-deficient cells with or without SR-BI overexpression. Disruption of cell surface heparan sulfate proteoglycans or blockage of apolipoprotein E-mediated lipoprotein binding also did not abolish the enhanced remnant HDL binding. Our observations indicate that remodeling of triglyceride-enriched HDL by hepatic lipase may result in enhanced binding, internalization, and degradation in tissues involved in HDL catabolism, contributing to rapid clearance and overall lowering of plasma HDL cholesterol in insulin resistance and hypertriglyceridemia.
Reticulate purpura, cryoglobulinaemia and livedo reticularis
Authors: E.L. SPEIGHT, C.M. LAWRENCE
Journal: British Journal of Dermatology (1993)

Two patients with type I cryoglobulinaemia are described, both of whom presented with purpura in a reticulate distribution on the legs, resembling the pattern of physiological livedo. It appeared that increased cooling due to sluggish blood flow in areas of the skin corresponding to the blue areas of physiological livedo may have caused the localization of cryoprecipitate at these sites. To investigate the pathogenesis of the net-like pattern of purpura, three subjects with physiological livedo reticularis of the thighs were studied with a laser-Doppler velocimeter. In two subjects, mean blood flux in the blue areas was 21% (P>0·01) and 26% (P>0·02) lower than in adjacent white areas, whereas in the third there was no significant difference. The cutaneous features of cryoglobulinaemia. and the mechanism of the reticulate purpura in this condition, are discussed.
Sex, hormones, and repolarization
Authors: T Pham
Journal: Cardiovascular Research (2002)

There is increased awareness of the impact of gender and gonadal steroids on human cardiac rhythm and arrhythmias; e.g., drugs that prolong repolarization induce torsades de pointes (TdP) more frequently in women than men; female gender is an independent risk factor for syncope and sudden death in the congenital long QT syndrome; and the higher propensity toward arrhythmia in normal females is associated with fundamental differences in repolarization such that rate-corrected QT intervals are longer in females than males. Mechanisms underlying these differences are incompletely defined but are believed to involve gonadal steroids. This review discusses recent advances and prospects for further elucidation of the influence of gender and gonadal steroids on ventricular repolarization and arrhythmias.
Levels of retinol-binding protein 4 and uric acid in patients with type 2 diabetes mellitus
Authors: Ching-Chu Chen, Jer-Yuarn Wu, Chwen-Tzuei Chang, Fuu-Jen Tsai, Tzu-Yuan Wang, Yi-Min Liu, Huai-Chih Tsui, Rong-Hsing Chen, Shyh-Ching Chiou
Journal: Metabolism (2009)
Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients
Authors: Augusto B. Federici, Pier M. Mannucci, Giancarlo Castaman, Luciano Baronciani, Paolo Bucciarelli, Maria T. Canciani, Alessandro Pecci, Peter J. Lenting, Philip G. De Groot
Journal: Blood (2008)
Fatal Aspergillosis in a Patient with SARS Who Was Treated with Corticosteroids
Authors: Huijun Wang, Yanqing Ding, Xin Li, Lei Yang, Wenli Zhang, Wei Kang
Journal: New England Journal of Medicine (2003)

To the Editor: We report the case of a patient with severe acute respiratory syndrome (SARS) who died of aspergillosis after prolonged treatment with corticosteroids. The patient was a 39-year-old male physician based at the intensive-care unit of a small hospital in Guangzhou, China; he had no concurrent medical illness. Many patients with SARS were admitted to the hospital where he worked during the eight weeks before April 4, 2003, when he presented with a sore throat and a low-grade fever (37.3°C). Five days later, he had a high fever (38.5°C) and a low leukocyte count (3.4 ×109 per liter; . . .
Abstract 105: Serum retinol and risk of head and neck cancer.
Authors: Jeffrey S. Chang, Jenn-Ren Hsiao, Chun-Yen Ou, Tung-Yiu Wong, Sen-Tien Tsai, Hung-I Lo, Cheng-Chih Huang, Wei-Ting Lee, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang
Journal: Cancer Research (2013)

Abstract Background: Head and neck cancer (HNC), including cancer of the oral cavity, pharynx, and larynx, is one of the leading cancers in the world. The known risk factors, including alcohol, betel quid, and cigarette, account for the majority of the HNC cases. However, the biological mechanisms regarding the carcinogenic effects of these agents in the development of HNC are not completely understood. Retinoic acid is involved in cell growth, differentiation, and apoptosis, which when dysregulated may lead to the development of cancer. Studies have shown that alcohol, betel quid, and cigarette can affect either the metabolism or the function of retinoic acid pathway. The current analysis evaluated the association between serum retinol and HNC risk and assessed whether this association can be modified by alcohol, betel quid, or cigarette. Methods: 93 incident cases of HNC and 79 sex- and age- frequency matched controls were recruited from the department of otolaryngology and department of stomatology. Information on the use of alcohol, betel quid, and cigarette was collected by in-person interviews. Serum retinol levels were measured using high performance liquid chromatography. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with serum retinol levels. Additional analyses were performed stratified by alcohol, betel quid, and cigarette. Results: Compared to controls, HNC cases had a lower level of serum retinol (Median for HNC cases: 811 ug/l vs. median for controls: 901 ug/l, Wilcoxon rank-sum P = 0.04). For every 100 ug/l increase, the risk of HNC was reduced by 8% (OR = 0.92, 95% CI: 0.83-1.02). The OR was 0.5 (95% CI: 0.24-1.06) comparing the highest tertile of serum retinol level to the lowest tertile. A lower HNC risk associated with higher serum retinol levels was observed among never alcohol drinkers (For every 100 ug/l increment, OR = 0.80, 95% CI: 0.66-0.96) but not among regular alcohol drinkers (For every 100 ug/l increment, OR = 0.98, 95% CI: 0.86-1.13). Conclusion: Higher levels of serum retinol are associated with a reduced risk of HNC. Alcohol consumption obliterates the inverse association between serum retinol and HNC risk, possibly by disrupting the metabolism of retinoic acid pathway. Citation Format: Jeffrey S. Chang, Jenn-Ren Hsiao, Chun-Yen Ou, Tung-Yiu Wong, Sen-Tien Tsai, Hung-I Lo, Cheng-Chih Huang, Wei-Ting Lee, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang. Serum retinol and risk of head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 105. doi:10.1158/1538-7445.AM2013-105
Enhancement of fluorinated Pyrimidine-Induced Cytotoxicity by Leucovorin in Human Colorectal Carcinoma Cell Lines
Authors: J.-G. Park, J. M. Collins, A. F. Gazdar, C. J. Allegra, S. M. Steinberg, R. F. Greene, B. S. Kramer
Journal: JNCI Journal of the National Cancer Institute (1988)

Reduced folates have been shown to increase the cytotoxicity of 5-fluorouracil (5-FU) by stabilizing the 5-fluoro-2′-deoxyuridine-5′-monophosphate-thymidylate synthase complex, thus increasing the block in the DNA synthetic pathway. Using an in vitro colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay, we tested the effects of 5-FU and 5-fluoro-2′-deoxyuridine (FdUrd) with and without leucovorin (LV) on a panel of 11 human colorectal carcinoma cell lines. The effect of LV on 5-FU and FdUrd was quantitatively similar. A clinically achievable level of LV (20 μM) increased the cytotoxicity in all three replicate experiments in 10 of the 11 cell lines (P < .05, binomial test). LV alone at a concentration of 20 μM had no effect on cell survival. In three cell lines, 50% inhibition of growth occurred at a clinically achievable area under the curve of 5-FU alone. With the addition of LV, one additional cell line showed 50% growth inhibition at a clinically achievable level of 5-EU. Hence large clinical trials may be necessary to detect a significant improvement in survival as a result of adding LV to the fluorinated pyrimidines. [J Nail Cancer Inst 188;80:1560–1564]
Genomes of 100 000 people will be sequenced to create an open access research resource
Authors: I. Torjesen
Journal: BMJ (2013)

An ambitious genome project launched in the United Kingdom this week aims to sequence the DNA of 100 000 people and publish that information as a free research resource that will be able to be accessed by anyone.

The genetic information will be linked to medical and other phenotypic information about the donors to enable researchers to use the material to help identify genes linked to medical conditions, develop new treatments, and facilitate improvements in personalised medicine.

Stephan Beck, director of Personal Genome Project UK (PGP-UK) and professor of medical genomics at University College London’s Cancer Institute, said, “This project is important for a number of reasons. It will establish the practice of open consent in the UK and enable medical advancement through meeting science’s need for ‘richer’ data.”

Speaking to the BMJ ahead …
Medicine in the USA: historical vignettes. X. The changing scene
Authors: L. S. King
Journal: JAMA (1983)

If we had to find a single date to distinguish the old medicine from the new, the year 1886 would serve quite well. Of the innumerable events that occurred in that year, I would regard two as especially symbolic: the death of Austin Flint, Sr (1812-1886) and the founding of the American Association of Physicians (AAP). Austin Flint, still remembered in connection with the heart murmur that bears his name, represented the old school of physicians that included William Gerhard (1809-1872), Alfred Stillé (1813-1900), William Pepper, Sr (1810-1864), Alonzo Clark (1807-1887), and Henry I. Bowditch (1808-1892). Oliver Wendell Holmes (1809-1894) could also be included in this group. These men were all teachers, and they contributed to the medical literature with textbooks or essays or both. With the exception of Holmes, all these men were practicing physicians, leaders in the profession at a time when laboratory investigation had made no impression
Liver-specific loss of β-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice
Authors: Shigeki Sekine, Billy Yu‐Ang Lan, Melanie Bedolli, Sandy Feng, Matthias Hebrok
Journal: Hepatology (2006)

There is accumulating evidence that Wnt/β-catenin signaling is involved in the regulation of liver development and physiology. The presence of genetic alterations resulting in constitutive β-catenin stabilization in human and murine liver tumors also implicates this pathway in hepatocyte proliferation. In the present study, we generated hepatocyte-specific β-catenin knockout mice to explore the role of β-catenin in liver function. Conditional knockout mice were born at the expected Mendelian ratio and developed normally to adulthood, indicating β-catenin is dispensable for essential liver function under normal breeding conditions. However, the liver mass of knockout mice was 20% less than those of mice in the control groups. Expression analysis revealed loss of genes required for glutamine synthesis in knockout mice. Loss of the liver glutamine synthesis pathway did not affect the blood ammonia level in mice fed a standard diet, yet, knockout mice showed significantly elevated blood ammonia levels with high-protein dietary feeding. Furthermore, the expression of two cytochrome P450 enzymes, CYP1A2 and CYP2E1, was almost completely abolished in livers from hepatocyte-specific β-catenin knockout mice. Consequently, these mice were resistant to acetaminophen challenge, confirming the requirement of these cytochrome P450 enzymes for metabolism of xenobiotic substances. In conclusion, in addition to regulating hepatocyte proliferation, β-catenin may also control multiple aspects of normal liver function. (HEPATOLOGY 2006;43:817–825.)
Blame My Brain: The Amazing Teenage Brain Revealed
Authors: Lesley Morrison
Journal: BMJ (2005)

W ritten for teenagers but invaluable reading for those coping with them—parents, doctors, and teachers— Blame My Brain , a guide to the biology behind teenage behaviour, is informative, accessible, interactive, and fun. There are self administered “tests,” scientific explanations (including wonderful images of trees to depict brain development), useful advice about emotions, sleep, risk, and harmful behaviours, and guidance about websites and other sources of reliable information. I am a parent of three teenagers, and many of its stories about getting risk in proportion rang bells for me.
Prerenal Failure: A Deleterious Shift from Renal Compensation to Decompensation
Authors: Franklin H. Epstein, Kamal F. Badr, Iekuni Ichikawa
Journal: New England Journal of Medicine (1988)

TRADITIONALLY, the term "prerenal failure" was used to describe a clinical situation in which the structurally intact kidney fails as a result of an impairment in glomerular perfusion. The decreased delivery of blood to the glomerulus was thought to precipitate a fall in the glomerular filtration rate, with subsequent development of azotemia. Our current understanding of this syndrome, however, is much more complicated than this earlier, simplistic formulation, in which renal function was viewed as being generally subservient to alterations in the systemic circulatory status, particularly cardiac output. In addition to the retention of salt and water, induced by adaptations . . .
Abstract 44: Towards novel marker discovery from phylogenetic analysis of heterogeneous tumor samples
Authors: Ayshwarya Subramanian, Stanley Shackney, Russell Schwartz
Journal: Cancer Research (2011)

Abstract Computational methods based on phylogenetics, or the inference of evolutionary trees, have been useful for inferring likely pathways of tumor progression, but their use has been limited by our inability to precisely characterize the mutational states of individual cells in heterogeneous tumor samples. We describe a novel approach to tumor phylogenetics using computationally inferred sub-populations of cells derived from whole-genome data on heterogeneous tumor samples. We previously proposed a strategy for computationally separating cell types from heterogeneous tumor samples and inferring genome-wide profiles of RNA expression or DNA copy number for these discrete cell populations from profiles of the full tumor samples. In the present work, we extend this method by showing how one can use these computationally inferred cell states to identify markers informative of progression state and use them in phylogenetic analysis of tumor samples. We demonstrate the approach on a publicly available data set of array comparative genome hybridization (aCGH) data profiles applied to sectioned ductal breast carcinomas (Navin et al., 2010; NCBI GEO GSE16672). Our approach begins by applying our previously described method for cell type separation to generate inferred profiles of six cell types, and computationally inferring virtual aCGH profiles for these types. We then scan over sliding windows of 20 consecutive probes per window, identifying windows for which probe values are significantly aberrant relative to diploid by a modified chi-squared test (p-value 0.001 with Bonferroni correction), and merging overlapping windows to identify phylogenetically informative amplicons. We then identify, for each amplicon, those components that have significantly aberrant copy number by Gaussian test with diploid mean (p-value 0.001). Finally, the identified amplicon states for the inferred cell types, as well as an additional all-diploid normal type, are used as input for a maximum parsimony phylogenetic tree reconstruction using the PAUP package with 300 bootstrap replicates. The method applied to the Navin et al. data identified 15 amplicons phylogenetically informative for breast tumor progression. Bootstrap replicates from the phylogenetic tree reconstruction reveal a robust grouping of cell states into three distinct subgroups and suggest several possible progression pathways by which the identified amplicons may successively accumulate in particular breast cancer sub-types. Continuing work will examine robustness of the inferred markers and pathways to independent data sources. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 44. doi:10.1158/1538-7445.AM2011-44