tbuckley/cabot-search huggingface dataset:
Abstract 3070: Simultaneous amplification of multiple genetic/epigenetic tumor markers in a single reaction for high throughput genotyping and aberrant methylation profiling
Authors: Liansen Liu, Chunmei Liu, Junko Stevens, Jonathan T. Wang
Journal: Cancer Research (2011)

Abstract Matching appropriate therapeutic regimes with tumor genotypes and epigenotypes is of great medical and economical importance. A prerequisite for this approach is thorough and accurate genotype and epigenotype profiling of tumor specimens, which should be performed in precisely defined homogeneous tumor cell populations with minimum non-tumor cell contaminations. However, this can be very challenging due to the genetic and epigenetic heterogeneities and the scarcity of homogeneous tumor cells within a tumor specimen. Multiplex PCR allows high throughput profiling by maximizing the number of targets/reaction in each sample and can reduce the limitations of such sample shortage. Although several multiplex PCR kits have been commercially available for this purpose for some time, their usefulness is restricted by small amplicon size range, less satisfactory amplification uniformity of different amplicons, and occasional failure in amplifying some amplicons, or false positive amplifications. To solve these problems, we have devised a highly specific, optimization-free multiplex PCR formulation (Applied Biosystems Platinum® Multiplex PCR Master Mix) with novel reaction chemistry. We show here that this new formulation is excellent for simultaneous amplification and high throughput profiling of SNPs, deletions, insertions and their wild types of many targets in a single reaction in terms of robustness, uniformity, amplicon size range, compatibility with amplicon GC contents, and the reduction of non-specific primer dimers and false positive/negative products in multiplex PCR. In combination with a primer system of varied lengths and compositions of 5’ stem-loop tag sequences, we demonstrate that even mixtures of multiple adjacent or overlapping alleles in the same locus of EGFR/KRAS/BRAF mutations can be specifically amplified in the same reaction and distinguished by amplicon size differentiation in a single lane of an agarose gel. Moreover, using primer sets specific for methylated and converted DNA, and those specific for unmethylated and converted DNA, we demonstrate that EGFR/KRAS/BRAF mutations and their associated promoter methylation status can be amplified from bisulfite-treated genomic DNA of colon cancer cell lines in a single reaction. In conclusion, the Applied Biosystems Platinum® Multiplex PCR Master Mix and the stem-loop primer system are a “best in class” solution to simultaneous amplification of various types of genetic and epigenetic tumor markers of multiple targets for high throughput genotyping and aberrant methylation profiling. 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 3070. doi:10.1158/1538-7445.AM2011-3070
LEAD STUDIES
Authors: Joseph C. Aub, Paul Reznikoff, Dorothea E. Smith
Journal: The Journal of Experimental Medicine (1924)

It appears, from the investigations in other laboratories, that the anemia observed in cases of lead poisoning is due to destruction of blood rather than to diminished production of blood. The method of poisoning cells in vitro with lead was adopted in order to study this phenomenon, and distinct effects were thereby obtained, even when only 0.001 mg. of lead is added to approximately 5 billion washed red corpuscles. In order to obtain optimum results the usual dosage employed was ten times this or 0.01 mg. per 5 billion cells. The following changes were observed in cells so treated. 1. Such a marked increase in the resistance to hypotonic salt solution develops that complete hemolysis does not occur until the cells are exposed to a saline solution of 0.05 per cent. Untreated cells are completely hemolyzed in 0.25 or 0.225 per cent saline. 2. This reaction is quantitative and varies with the concentration of lead used. Under the conditions of our experiments this phenomenon seems to be unique. The effects of arsenic are very slight in comparison. 3. While from this reaction it may be concluded that lead increases cellular resistance, it also appears that it shortens the life of blood cells. This may be demonstrated by the much more rapid appearance of hemolysis than normal when the cells are merely allowed to stand in Ringer solution of any dilution. 4. In rabbits with acute lead poisoning these same phenomena may be noted in vivo. 5. Both phenomena may be changed in vitro by varying the time and temperature of the reaction and the concentration of lead, as Fici has already pointed out. 6. If normal cells stand in Ringer solution for 6 hours something diffuses into the solution which largely reduces the action of lead. After repeated washing these cells react with lead in the usual manner. 7. Small amounts of serum react with lead and eliminate its effects. Red blood cells, treated with a mixture of lead and blood serum, show normal hemolysis in hypotonic salt solution. 8. When lead is added to whole blood the only evidence of this neutralization is a marked decrease in the intensity of the reaction. This is probably explained by the fact that since both serum and cells are present together, the lead reacts with both simultaneously. This in turn explains how the reaction may occur in vivo. 9. The change in hemolysis does not appear in the blood of all species of animals. In the species in which it does occur, anemia and stippling of the red cells also tend to develop readily during lead intoxication. 10. In vitro, cells which have been exposed to lead are far more fragile than normal blood cells. Slight trauma causes them to hemolyze. In vivo this is probably an important causal factor in the increased destruction of blood and in the anemia of acute lead poisoning. 11. The serum of a rabbit which has been immunized to human blood, causes more rapid and complete hemolysis in cells treated with lead than in the control cells. No satisfactory explanation for this has been found.
Hepatorenal and Glomerulotubular Imbalance
Authors: Stanley E. Bradley
Journal: New England Journal of Medicine (1973)

The "hepatorenal syndrome" presents an easily recognized but infinitely perplexing picture that grows more confusing despite increasing refinement and sophistication of analysis and therapy. The initial stumbling block is the diversity and number of conditions that the term embraces. The liver and kidney both serve as major excretory routes and are therefore simultaneously susceptible to injury by a large variety of toxic agents that can produce a clinically obvious combination of hepatic and renal failure. Each possesses a large vasculature and receives approximately one quarter of the cardiac output each minute in resting man. As a consequence, each is peculiarly . . .
Seasonal variation in scabies: reply from authors
Authors: D. Mimouni, I. Grotto, M. Gdalevich
Journal: British Journal of Dermatology (2004)

Sir, In our article on the seasonality trends of scabies we have used the database of the Israel Defence Forces (IDF).1 In an earlier study, one which dealt with global scabies epidemiology,2 the general IDF experience with this disease was elaborated, and earlier reports both from the IDF and other sources were cited. This concise communication originated from the fact that in the IDF, scabies is a routinely notifiable condition. Therefore, the trends and seasonality analysis is based on real incidence data, which differs from other reports on the subject3 that are based mainly on conveniency samples or general estimates, and are thus subject to bias and error.1, 2 The hypothesis of sexual transmission of scabies, first reported in 1978,4 has been suggested to explain the higher prevalence of the disease during the winter months. This theory, however, was not based on observations of increased sexual promiscuity during this interval, as suggested by Dr Downs.
EU to suspend hundreds of drug authorisations after doubts over clinical studies in Hyderabad
Authors: R. Watson
Journal: BMJ (2015)

The European Commission is preparing to suspend the marketing authorisations for more than 700 generic drugs after serious doubts emerged over the validity of the clinical studies conducted by GVK Biosciences in Hyderabad, India. The decision, which is expected within the next three to four weeks, will be legally binding throughout the 28 member European Union.

The unexpectedly tough action was based on a recommendation from the London based European Medicines Agency. At the commission’s request the …
RELATIVE EFFICACY OF BLOOD, URINE, RECTAL SWAB, BONE-MARROW, AND ROSE-SPOT CULTURES FOR RECOVERY OF SALMONELLA TYPHI IN TYPHOID FEVER
Authors: RobertH. Gilman, Miguel Terminel, MyronM. Levine, Pablo Hernandez-Mendoza, RichardB. Hornick
Journal: The Lancet (1975)
The "Pink Spot," 3,4-Dimethoxyphenylethylamine, Common Tea, and Schizophrenia
Authors: JAMES R. STABENAU, CYRUS R. CREVELING, JOHN DALY
Journal: American Journal of Psychiatry (1970)

Several studies of schizophrenic and normal patients suggested a plant food dietary source for urinary 3, 4-DMPEA. The authors' study of three nonschizophrenics found this urinary amine (positively identified by mass spectrometry) present during free diet plus tea ingestion and not present during controlled diet except when tea was being ingested. They conclude that urinary 3, 4-DMPEA has an exogenous plant source and that its presence is not primarily related to schizophrenia.
Topical Anesthesia and Swallowing
Authors: Michael R. Cohen
Journal: JAMA (1976)

ABSTRACT To the Editor.— Modern cancer chemotherapy, as well as local surgical procedures, antimicrobial therapy, and local irradiation, is increasing the incidence of stomatitis, sore throat, and dysphagia.The use of lidocaine hydrochloride (Xylocaine Viscous) to induce topical anesthesia of the pharynx prior to eating can result in a potentially hazardous and fatal situation.Report of a Case.— A 66-year-old man complained of a sore throat and dysphagia after diagnostic bronchoscopy. Lidocaine hydrochloride 2%, 5 ml three times daily before meals was prescribed. No other medications had been administered during the previous 24 hours. Just prior to his evening meal, the patient gargled and swallowed the prescribed dose and shortly thereafter began to eat his dinner that consisted of, among other things, toast, eggs, and milk. After his initial mouthful, he was unable to sense the food bolus in his pharynx, and thinking that it was swallowed, he resumed his breathing,
Neurological speech deficits as plot devices in novels
Authors: Richard Sainsbury, Christine Wyles, Gina Tillard
Journal: Journal of the Royal Society of Medicine (2012)

Stroke is a leading cause of death worldwide and a common cause of disability in adults in developed countries.1 Most strokes are not fatal and, in contrast to coronary artery disease and cancer, the major burden of stroke is chronic disability rather than death.2 It is unsurprising, therefore, that characters with stroke appear frequently in literature, although sometimes the diagnosis is wrong. In George Eliot's Silas Marner, for example, the title character is thought to suffer ‘strokes’ whereas the diagnosis is probably narcolepsy. There are a number of common themes in literary descriptions of people with stroke; first, the stroke is often brought on by high emotion or shock, but before the days of adequate treatment of hypertension, cerebral haemorrhage is likely to have been more common. Second, they frequently result in complete or partial loss of speech, which prevents the protagonist from imparting vital information or exposing villains. Third, they are often treated with bleeding if there is a doctor handy. Notable examples of this treatment are Billy Bones in Robert Louis Stevenson's Treasure Island, Squire Dornell in Thomas Hardy's short story The First Countess of Wessex and Prince Bolkonsky in Tolstoy's War and Peace. In the first two cases the treatment is apparently effective (although Bones dies a little while later of a second massive stroke when he receives the pirates ‘black spot’), although in reality the hypotension induced by bleeding would be dangerous and likely to extend the stroke if it was a cerebral infarct.

Stroke related speech deficits can be used by authors to influence a novel's plot. We discuss several prominent examples using well-known novels where this occurs.
Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms.
Authors: H A El-Fawal, S J Waterman, A De Feo, M Y Shamy
Journal: Environmental Health Perspectives (1999)

The interactions between the nervous and immune systems have been recognized in the development of neurodegenerative disease. This can be exploited through detection of the immune response to autoantigens in assessing the neurotoxicity of environmental chemicals. To test this hypothesis, the following questions were addressed. a) Are autoantibodies to nervous system (NS) antigens detected in populations exposed to environmental or occupational chemicals? In sera of male workers exposed to lead or mercury, autoantibodies, primarily IgG, to neuronal cytoskeletal proteins, neurofilaments (NFs), and myelin basic protein (MBP) were prevalent. These findings were confirmed in mice and rats exposed to either metal. b) Do autoantibodies to NS antigens relate to indices of exposure? In humans exposed to either metal, and similarly in exposed rats, titers of IgG against NFs and MBP significantly correlated with blood lead or urinary mercury, the typical indices of exposure. c) Do autoantibodies correlate with sensorimotor deficits? In workers exposed to lead or mercury, a significant correlation was observed between IgG titers and subclinical deficits. Doses of metals used in rat exposures were subclinical, suggesting that autoantibodies may be predictive of neurotoxicity. d) Is the detection indicative of nervous system pathology? In rats exposed to metals, histopathology indicated central nervous system (CNS) and peripheral nervous system (PNS) damage. In addition there was evidence of astrogliosis, which is indicative of neuronal damage in the CNS, and the presence of IgG concentrated along the blood-brain barrier, as indicated by immunostaining for antibodies. e) Are immune responses to NS antigens pathogenic? Immunoglobulin fractions from rat and human sera interfered with neuromuscular function. These studies suggest that the detection of autoantibodies to NS-specific antigens may be used to monitor the development of neurotoxicity to environmental chemicals and that immune mechanisms may be involved in the progression of neurodegeneration.
Deficiency in the Detection of Microalbuminuria by Urinary Dipstick in Diabetic Patients
Authors: Susan Selgren
Journal: Diabetes Care (2004)

We read with interest the letter from Comper et al. (1) that compared the performance of Bayer’s Microalbustix and CLINITEK Microalbumin urinalysis strips with a high-performance liquid chromatography (HPLC) method that allegedly detects nonimmunoreactive forms of albumin. The Comper et al. letter implies that the American Diabetes Association established the >95% detection criteria for semiquantitative microalbuminuria tests on the basis of this HPLC reference method.

This implication is misleading. The American Diabetes Association …
Protein Structure, Neighbor Effect, and a New Index of Amino Acid Dissimilarities
Authors: Xuhua Xia, Zheng Xie
Journal: Molecular Biology and Evolution (2002)

Amino acids interact with each other, especially with neighboring amino acids, to generate protein structures. We studied the pattern of association and repulsion of amino acids based on 24,748 protein-coding genes from human, 11,321 from mouse, and 15,028 from Escherichia coli, and documented the pattern of neighbor preference of amino acids. All amino acids have different preferences for neighbors. We have also analyzed 7,342 proteins with known secondary structure and estimated the propensity of the 20 amino acids occurring in three of the major secondary structures, i.e., helices, sheets, and turns. Much of the neighbor preference can be explained by the propensity of the amino acids in forming different secondary structures, but there are also a number of intriguing association and repulsion patterns. The similarity in neighbor preference among amino acids is significantly correlated with the number of amino acid substitutions in both mitochondrial and nuclear genes, with amino acids having similar sets of neighbors replacing each other more frequently than those having very different sets of neighbors. This similarity in neighbor preference is incorporated into a new index of amino acid dissimilarities that can predict nonsynonymous codon substitutions better than the two existing indices of amino acid dissimilarities, i.e., Grantham's and Miyata's distances.
Defective Nonoxidative Leucine Degradation and Endogenous Leucine Flux in Cirrhosis During An Amino Acid Infusion
Authors: Arthur J. McCullough, Kevin D. Mullen, Satish C. Kalhan
Journal: Hepatology (1998)

The metabolic fate of leucine's first and second carbon may be different depending on the tissue in which leucine is metabolized, as well as the prevailing hormonal milieu of that tissue. However, previous studies of leucine kinetics in humans have used only leucine labeled (as tracer) at the first carbon position. Because cirrhosis is associated with factors (such as insulin resistance and altered fuel substrate utilization) that may influence how leucine is degraded, the kinetics of leucine's first and second carbon using a simultaneous infusion of [1-14C] leucine and [2-13C] leucine were studied in the postabsorptive state and during an amino acid infusion in 6 stable cirrhotic patients and 6 matched controls. The data were normalized for different body compartments that were quantified from the dilution of H2 [180] and bromide. The body cell mass, but not body weight or fat-free body mass, was decreased in cirrhosis (P < .001). In response to the amino acid infusion, total leucine appearance from proteolysis and leucine's incorporation into protein increased significantly in both groups, but were higher in cirrhotic patients. Endogenous protein breakdown decreased in normals but remained unchanged in cirrhosis. These alterations in leucine metabolism became more prominent when data were expressed based on the body cell mass rather than on body weight. The oxidation of leucine's first carbon (C1) was decreased in cirrhosis, but the oxidation of leucine's second carbon (C2) did not differ between groups during both the postabsorptive period and the amino acid infusion, while nonoxidative leucine degradation [the difference between the oxidation of leucine's (C1) and (C2)] was also decreased in cirrhosis. In addition, there was a positive correlation between nonoxidative leucine degradation (which represents leucine incorporation into fat), and the respiratory quotient obtained from indirect calorimetry (r = .87; P < .001). These data suggest that the extent of leucine carbon oxidation is dependent on whether fat or carbohydrate is the prevailing fuel substrate. In addition, cirrhotic patients have decreased nonoxidative leucine degradation and are unable to suppress endogenous protein breakdown normally in response to amino acid administration. These abnormalities may contribute to the diminished fat stores and body cell mass commonly observed in cirrhosis.
Response to the Diabetes Nutrition Study Group of the European Association for the Study of Diabetes
Authors: Marion J. Franz, John P. Bantle
Journal: Diabetes Care (2002)

We welcome the European perspective, although we do not completely share it. We agree with the statement of Mann et al. (1) that “meticulously conducted and controlled human studies of people with diabetes that involve dietary manipulations over a period of weeks or months… provide the most powerful evidence.” However, we take issue with several concerns they express. First, we take issue with the statement that it is important to consider how recommendations are likely to be interpreted by health professionals and patients. Second, we continue to believe that the total amount of carbohydrate is more important than the source or type. Third, we continue to believe that sucrose does not need to be restricted, relative to other carbohydrates, because of concern about aggravating hyperglycemia.

It was an initial determination of the American Diabetes Association Task Force that it was our task to write, as accurately as possible, evidence-based nutrition principles and recommendations. The implementation of these principles and recommendations was to be determined by health professionals in their individualized nutrition counseling with patients. Furthermore, we concluded that patients have the right to read and know accurate nutrition information. With this …
Quantitative Imaging of Na/I Symporter Transgene Expression Using Positron Emission Tomography in the Living Animal
Authors: Thomas Groot-Wassink, Eric O Aboagye, Yaohe Wang, Nicholas R Lemoine, Andrew J Reader, Georges Vassaux
Journal: Molecular Therapy (2004)

Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem γ counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem γ counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies.
Classic Papers in Geriatric Medicine With Current Commentaries
Authors: Kristin Robie
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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