tbuckley/cabot-search huggingface dataset:
P5-01-12: Identification of an ATM Activation Subtype in PTEN Mutant Breast Tumours.
Authors: N McCabe, SM Walker, N Goffard, K Wikstrom, C Greenan, T Delaney, M McCarthy, F McDyer, L Hill, S Deharo, V Proutski, K Keating, P Mullan, DP Harkin, RD Kennedy
Journal: Cancer Research (2011)

Abstract Background PTEN is frequently lost in cancer cells through genetic mutation or epigenetic silencing. Loss of PTEN function has been widely reported to cause up-regulation of the PI3K/AKT signalling pathway resulting in increased cell growth, proliferation and survival. More recently it has been reported that PTEN null cells demonstrate genomic instability through increased ROS and oxidative stress induced DNA damage. The aim of this study was to identify a biomarker for PTEN status in human breast cancers. Materials and Methods A metagene representing ATM activation was generated from public cell line data of AT fibroblasts treated with gamma-irradiation. This was used to perform hierarchical clustering analysis of a public DNA microarray profiling dataset with known PTEN IHC status. The metagene was validated in PTEN wildtype and null breast cancer cell lines. Results We found that PTEN null cells have elevated levels of ROS and furthermore activation of the DNA damage signalling kinase, ATM. In agreement with this, the ATM metagene signature correlated with PTEN mutation in breast cancer tumours. Scoring of PTEN wildtype and null breast cancer cell lines using the metagene correlated with ATM activation and sensitivity to inhibition of ATM. Furthermore we show that inhibition of ATM caused DNA damage, cell cycle arrest and apoptosis in PTEN deficient cells suggesting a novel therapeutic strategy. Conclusion These observations suggest that ATM may represent a therapeutic target in PTEN deficient tumours and furthermore ATM activation may also be an important biomarker of PTEN mutation or loss in breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-12.
Fatty Acid Biosynthesis in Human Leukocytes*
Authors: Philip W. Majerus, Rene Lastra R.
Journal: Journal of Clinical Investigation (1967)

Extracts from human leukocytes have been examined for the enzymes of de novo fatty acid biosynthesis. These extracts do not catalyze the synthesis of long-chain fatty acids because they lack acetyl CoA carboxylase, the first enzyme unique to the fatty acid synthesis pathway. Since these cells cannot form malonyl CoA, they are unable to synthesize long-chain fatty acids. This inability can be corrected by addition of either purified acetyl CoA carboxylase from rat liver or malonyl CoA to leukocyte extracts. The incorporation of acetate-1-(14)C into fatty acids by intact leukocytes is shown to represent chain elongation of preformed fatty acids rather than de novo synthesis by the fact that 60-100% of the label incorporated resides in the carboxyl carbon of the fatty acids formed.Both mature leukocytes and erythrocytes are unable to synthesize fatty acids because of a lack of acetyl CoA carboxylase even though both contain the other enzymes of fatty acid synthesis. It is possible that a precursor hematopoietic cell may have the capacity to synthesize fatty acids de novo. This hypothesis is supported by the finding of acetyl CoA carboxylase activity in extracts from human leukemic blast cells.The leukocyte fatty acid synthetase activity from malonyl CoA of a number of normal volunteers and of patients with a variety of hematologic diseases is reported.
CHICAGO MEDICAL SOCIETY RESOLUTIONS ON PUBLIC HEALTH OFFICIALS
Authors: C.-E. A. Winslow
Journal: JAMA (1926)

<h3>To the Editor:</h3> —The Journal, November 21, under news, contains a somewhat lengthy resolution adopted by the council of the Chicago Medical Society, November 10, which is so misleading that I should like an opportunity to correct it. The resolution in question begins as follows: Whereas, the American Public Health Association at its annual meeting in St. Louis in October, 1925, listened to an address by one of its members favoring a new doctor in each community where a health officer is needed to be known as a Doctor of Public Health. It closes as follows: Resolved, That the Chicago Medical Society views with displeasure any move on the part of the American Public Health Association which may express a desire to replace physicians as health officials by laymen with D.P.H. licenses. Resolved, That a copy of this resolution be sent to the American Public Health Association, to all those
Host Perforin Reduces Tumor Number but Does Not Increase Survival in Oncogene-Driven Mammary Adenocarcinoma
Authors: Shayna E.A. Street, Nadeen Zerafa, Manuela Iezzi, Jennifer A. Westwood, John Stagg, Piero Musiani, Mark J. Smyth
Journal: Cancer Research (2007)

Abstract The concept of tumor immune surveillance has been supported by several recent studies in mice which show that immune effector mechanisms suppress hematologic malignancy. However, because the most common forms of human cancer are epithelial in origin, and comparatively very little data supports the immune surveillance of epithelial malignancies, we have chosen to evaluate the role of perforin-mediated cytotoxicity in the prevention of BALB/c Her2/neu-induced mammary cancer. Interestingly, perforin significantly delayed the onset of mammary tumorigenesis and reduced the number of mammary tumors without improving survival. Natural killer cell, but not CD8+ T cell, depletion resulted in a similar phenotype to perforin deficiency in this regard. Histologic analysis further indicated that the effect of perforin was most evident during the earliest stages of carcinogenesis rather than prior to or during the hyperplastic phase. This data suggests that perforin may mediate some suppression of epithelial carcinogenesis by intervening early in the tumor development process. [Cancer Res 2007;67(11):5454–60]
HYGIENE VERSUS DRUGS.
Authors: C. F. ULRICH
Journal: JAMA (1896)

The American people have been called a medicine-taking nation. If the quantity of drugs prescribed by physicians, the masses of patent medicines, the barrels of so called home remedies, such as teas, decoctions, infusions and other monstrosities, swallowed by the American people, were ascertained, collated, arranged and published in a book, it would strike the reader dumb with astonishment. The fact that any human body can survive the injection of such an endless variety of vegetable, animal and mineral poisons as are poured into the patient and unresisting stomach and thence distributed throughout the various channels, acting upon the digestive organs, the circulation and the nervous system, proves that man is indeed "fearfully and wonderfully made," and has much greater powers of resistance than we would believe possible. Let us suppose that an individual has what is commonly called a cold, which may be catarrh of the pharynx, the tonsils,
Cheap and effective method of weighing bed-bound patients.
Authors: D T Hansell, G D Smellie
Journal: BMJ (1982)

Death due to overdose of indoraminIndoramin (Baratol) is a recently introduced alpha'-adrenergic antagonist used to treat essential hypertension.I report a fatal case of self-poisoning with indoramin.This is the first such case to be de- scribed.
Geographic Variation in Mortality From Breast Cancer Among White Women in the United States
Authors: S. R. Sturgeon, C. Schairer, M. Gail, M. McAdams, L. A. Brinton, R. N. Hoover
Journal: JNCI Journal of the National Cancer Institute (1995)

For several decades, mortality from breast cancer has been higher in the northeastern part of the United States than in other regions, particularly the South. Rates have also been somewhat higher in the Midwest and West than in the South, especially among older women. The reasons for these geographic variations are not well understood.The objective of this study was to evaluate geographic differences in U.S. breast cancer mortality rates in 1987, after taking into account regional differences in the distribution of recognized breast cancer risk factors (e.g., late age at first live birth) and certain prognostic factors (e.g., mammography use).The 1987 breast cancer mortality rates for four regions of the country were obtained from the National Center for Health Statistics. Regional data on the distribution of breast cancer risk factors were obtained from 1987 National Health Interview Cancer Epidemiology Supplement interviews with 9778 white women aged 20-79 years. Regional data on the distribution of mammography use were obtained from 1987 National Health Interview Cancer Control Supplement interviews with 3795 white women aged 50-79 years.Age-adjusted mortality ratios (MRs) among women 50 years and older were 1.15, 1.18, and 1.30 in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among women 20-49 years old were 1.01, 1.08, and 1.07 in the West, Midwest, and Northeast, respectively, compared with the South. After adjustment for recognized risk factors and certain prognostic factors, MRs among older women were 1.13 (95% confidence interval [CI] = 1.04-1.23), 1.08 (95% CI = 1.01-1.16), and 1.13 (95% CI = 1.04-1.23) in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among younger women were 0.94 (95% CI = 0.76-1.16), 1.05 (95% CI = 0.92-1.18), and 0.99 (95% CI = 0.86-1.14), respectively.Before adjustment for regional differences in recognized risk factors and prognostic factors, mortality excesses among younger women in the Northeast, Midwest, and West were less than 10% compared with the South. After adjustment, MRs were near unity for all regions. Among older women, the excess mortality was more substantial before adjustment for relevant factors, ranging from 15% in the West to 30% in the Northeast. Approximately 50% of the excesses in the Northeast and Midwest and 10% of the excess in the West could be explained on the basis of regional differences in the prevalence of recognized breast cancer risk factors and prognostic factors. After adjustment for these factors, the magnitude of excess in breast cancer mortality in the Northeast (13%) was comparable to that in the West (13%) but still slightly higher than that in the Midwest (8%).
A new integrated system for three-dimensional echocardiographic reconstruction: Development and validation for ventricular volume with application in human subjects
Authors: Mark D. Handschumacher, Jean-Paul Lethor, Samuel C. Siu, Donato Mele, J.Miguel Rivera, Michael H. Picard, Arthur E. Weyman, Robert A. Levine
Journal: Journal of the American College of Cardiology (1993)
Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha.
Authors: L Eckmann, S L Reed, J R Smith, M F Kagnoff
Journal: Journal of Clinical Investigation (1995)

Infection with the protozoan parasite Entamoeba histolytica results in a high mortality worldwide. To initiate infection, E. histolytica trophozoites in the bowel lumen penetrate the epithelium, and cause extensive lysis of host cells. The acute amebic lesions in animal models are characterized by infiltration with inflammatory cells, particularly neutrophils. The acute host response is likely important for determining whether the infection will spread systemically, but little is known regarding the signals which initiate an acute inflammatory response to E. histolytica. In the studies reported herein, we used an in vitro model system to define the proinflammatory signals produced by epithelial and other host cells in response to infection with E. histolytica trophozoites. Coculture of human epithelial and stromal cells and cell lines with trophozoites is shown to increase expression and secretion of an array of chemoattractant and proinflammatory cytokines, including IL-8, GRO alpha, GM-CSF, IL-1 alpha, and IL-6. Moreover, high-level secretion of those cytokines is regulated by the paracrine action of cytolytically released IL-1 alpha. A second mechanism for trophozoite-induced IL-8 production involves trophozoite-target cell contact via a galactose-inhibitable amebic adherence protein, and appears to be mediated through increased intracellular calcium levels. These studies define novel mechanisms through which acute inflammation can be initiated in the host in response to a cytolytic pathogen, such as E. histolytica.
Screening haemodialysis patients for infection with human immune deficiency virus (HIV)
Authors: N.G. De Santo, G. Tarro, C. Giordano, G. Capodicasa, C. Esposito, G. Flaminio, G. Sodano, M.R. Caropreso, M. Pluvio, D. Giordano, A. Karpas
Journal: Journal of Infection (1987)
BMA criticises new visa requirements for overseas doctors
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

The BMA and the British Association of Physicians of Indian Origin (BAPIO) have condemned the speed at which new visa restrictions for overseas doctors have been introduced in the United Kingdom. The changes, which mean that doctors from outside the European economic area (EEA) who train in the UK will need a work permit, have been rushed through with little regard for doctors' welfare, the associations say.

The new rules, which were introduced on 3 April, bar NHS trusts from recruiting junior doctors from outside the EEA unless …
Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia
Authors: Julie Makani, Stephan Menzel, Siana Nkya, Sharon E. Cox, Emma Drasar, Deogratius Soka, Albert N. Komba, Josephine Mgaya, Helen Rooks, Nisha Vasavda, Gregory Fegan, Charles R. Newton, Martin Farrall, Swee Lay Thein
Journal: Blood (2010)
Locked-In or Locked-Out, But Present
Authors: Kenneth M. Heilman
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Helper T cells reacting to idiotype on IgG but not IgM.
Authors: T Saito, K Rajewsky
Journal: The Journal of Experimental Medicine (1985)

Immunization with an IgG1 but not an IgM monoclonal anti-NP (4-hydroxy-3-nitrophenyl acetyl) antibody induced idiotype-recognizing T helper cells, although these two antibodies carry the same variable regions. The T cells appear to react to an idiotype on the IgG1 but not the IgM antibody. They selectively enhance the expression of that idiotype in the IgG1 fraction of an in vitro anti-NP response.
Ursodeoxycholic acid and taurine as therapy for cholestatic liver disease Podda M, Ghezzi C, Battezzati PM, Crosignani A, Zuin M, Roda A. Effects of ursodeoxycholic acid and taurine on serum liver enzymes and bile acids in chronic hepatitis. Gastroenterology 1990;98:1044–1050
Authors: M Chan
Journal: Hepatology (1991)
3-Min step test and treadmill exercise for evaluating exercise-induced asthma
Authors: G. Tancredi, S. Quattrucci, F. Scalercio, G. De Castro, A.M. Zicari, E. Bonci, S. Cingolani, L. Indinnimeo, F. Midulla
Journal: European Respiratory Journal (2004)

A simple exercise test would be useful for detecting exercise-induced asthma, a common problem in asthmatic children. The current study compared the 3‐min step test with treadmill exercise for evaluating exercise-induced asthma in asthmatic children and assessed whether responses to both tests are influenced by baseline lung function and habitual physical activity. A series of 154 asthmatic children (84 male children; mean age 12.9±0.9 yrs) underwent a 3‐min step-test and treadmill testing on different days within a week at least 24 h apart. Before both tests each subject did spirometry to obtain the baseline forced expiratory volume in one second (FEV 1 ). After both exercise challenges all subjects did serial spirometry and the lowest FEV 1 recorded over time was used to calculate the fall in FEV 1 expressed as a percentage of the measured pre-exercise (baseline) value (% fall in FEV 1 ) and the area above the FEV 1 curve (AAC 0–30 min ) expressed as a percentage of the pre-exercise value. Changes in both exercise variables were also analysed in percentile subgroups defined by questionnaire answers on habitual physical activity in hours. The mean % fall in FEV 1 was significantly higher for treadmill exercise than for the step test (15.0±7.5 versus 11.7±5.9); and the AAC 0–30 min was larger for treadmill than for the step test (−261.6±139.9% versus −197.3±105.0% min). In all subgroups defined by habitual physical activity the mean % fall in FEV 1 decreased more after treadmill exercise than after the step test. After step test and treadmill exercise no significant correlation was found between % fall in FEV 1 and baseline lung function, or between % fall in FEV 1 among groups defined by habitual physical activity. Although the 3‐min step test yields a lower % fall in forced expiratory volume in one second (FEV 1 ) and a lower value of the area above the FEV 1 curve than treadmill testing, it is a quick, economical, reproducible and portable alternative procedure for identifying exercise-induced asthma in outpatients and epidemiological studies. Baseline lung function and habitual physical activity have no influence on the amount or duration of exercise-induced asthma.
PDGF/VEGF signaling controls cell size in Drosophila
Authors: David Sims, Peter Duchek, Buzz Baum
Journal: Genome biology (2009)

Abstract Background In multicellular animals, cell size is controlled by a limited set of conserved intracellular signaling pathways, which when deregulated contribute to tumorigenesis by enabling cells to grow outside their usual niche. To delineate the pathways controlling this process, we screened a genome-scale, image-based Drosophila RNA interference dataset for double-stranded RNAs that reduce the average size of adherent S2R+ cells. Results Automated analysis of images from this RNA interference screen identified the receptor tyrosine kinase Pvr, Ras pathway components and several novel genes as regulators of cell size. Significantly, Pvr/Ras signaling also affected the size of other Drosophila cell lines and of larval hemocytes. A detailed genetic analysis of this growth signaling pathway revealed a role for redundant secreted ligands, Pvf2 and Pvf3, in the establishment of an autocrine growth signaling loop. Downstream of Ras1, growth signaling was found to depend on parallel mitogen-activated protein kinase (MAPK) and phospho-inositide-3-kinase (PI3K) signaling modules, as well as the Tor pathway. Conclusions This automated genome-wide screen identifies autocrine Pvf/Pvr signaling, upstream of Ras, MAPK and PI3K, as rate-limiting for the growth of immortalized fly cells in culture. Since, Pvf2 / 3 and Pvr show mutually exclusive in vivo patterns of gene expression, these data suggest that co-expression of this receptor-ligand pair plays a key role in driving cell autonomous growth during the establishment of Drosophila cell lines, as has been suggested to occur during tumor development.
New health minister faces crisis in Israel
Authors: J Siegel-Itzkovich
Journal: BMJ (1994)

Israel has appointed a new health minister. Dr Ephraim Sneh is the first physician ever to hold the post in Israel, and he takes over four months after the previous minister resigned when his version of a national health insurance bill was rejected.

Dr Sneh, who served as head of the West Bank's civil administration and has been a member of the Labour party for two years, spent 18 years as a physician in Israel's defence forces, during which time he acted as head of the medical team that took part in the rescue of Israeli hostages in Entebbe, Uganda, in 1976. He comes to office at a time when the country's largest health insurer is teetering on the brink of bankruptcy and asking to …
PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS
Authors: S. C. Madden, F. W. Anderson, J. C. Donovan, G. H. Whipple
Journal: The Journal of Experimental Medicine (1945)

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency. When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion. An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine.HCl.H(2)O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine.HCl.H(2)O 1, l(+)-arginine.HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm. Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8). Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction. Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance. Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved.