tbuckley/cabot-search huggingface dataset:
Abstract 3711: New neocryptolepine derivatives: Mechanism of cytotoxicity and the best substituent
Authors: Okada Masashi, Zhen-Wu Mei, Tomohito Odawara, Taihei Tominaga, Takayuki Kudoh, Ibrahim El-Sayed, Tsutomu Inokuchi, Masaharu Seno
Journal: Cancer Research (2010)

Abstract Since cancer is one of the major causes of death all over the world, discovery of effective anticancer agents has long been desired. Plant alkaloids are often considered to be potent candidates. Cryptolepsis sanguinolenta is a medicinal plant which habits in West Africa. In a traditional medicine, a decoction of the root of C. sanguinolenta is used to treat fevers. Neocryptolepine, one of the plant alkaloids extracted from the root of C. sanguinolenta, are reported to have several activities such as DNA intercalation, anti-malaria and Topoisomerase inhibition. Topoisomerase (Topo) is double helical DNA relaxation enzyme and responsible for DNA replication, transcription and recombination. Inhibition of Topoisomerase is one of the mechanisms of anti-cancer agent. In this research, we synthesized a number of neocryptolepine derivatives with several substituents added to the backbone and evaluated their inhibitory activities of cell growth and topoisomerase. The derivatives were synthesized from indole carboxylic acid methyl ester and aniline derivatives through well-known procedure. DNA relaxation activity of the derivatives was assessed on plasmid pBR322 DNA in the presence of TopoI or TopoII. Cell growth inhibition was assessed on six cancer cell lines; K562, LNCaP, MDA-MB-453, SKOv3, A549, and WiDr. Those cell lines were exposed to the derivatives for 72 hours and their 50% survival rate IC50 was estimated by MTT colorimetric assay. Although no derivative inhibited TopoII activity, 12 derivatives inhibited TopoI activity. The inhibition of TopoI by neocryptolepine derivatives appears to be caused by their planar organic constitution, which enable derivatives to intercalate into double helix of DNA. Cell growth inhibitory effect has been improved in some derivatives that received modification at their substituent. Those derivatives also exhibited TopoI inhibition correlating with inhibition of cell growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3711.
A new, noninvasive technique for inducing post-extrasystolic potentiation during echocardiography.
Authors: P F Cohn, G H Angoff, P M Zoll, L J Sloss, J E Markis, T B Graboys, L H Green, E Braunwald
Journal: Circulation (1977)

Left ventricular function was evaluated in 34 patients with the echocardiogram, and an external mechanical cardiac stimulator was used to induce a ventricular premature contraction (VPC) noninvasively. Extent of post-extrasystolic potentiation (PESP) was determined by comparing systolic dimensional shortening and ejection fraction of the sinus beat preceding the VPC to that of the potentiated beat which followed it. Using this technique, a VPC could be introduced into the cardiac cycle of 30 of the 34 patients, six of whom were free of obvious cardiac disease and 24 of whom had valvular, coronary or myopathic heart disease. The only complication observed was mild breast ecchymosis in a female patient. Systolic dimensional shortening and ejection fraction increased from control values by an average of 21% and 17% respectively, with a range of 0-100%. The degree of PESP was very reproducible in repeat studies and when the same patients were subsequently evaluated during a spontaneously occurring or catheter-induced VPC. The technique can safely and reliably induce post-extrasystolic potentiation during echocardiography and is a potentially important adjunct to the noninvasive evaluation of left ventricular function.
Subclinical Changes in the Juvenile Crystalline Macular Dystrophy in Sjögren–Larsson Syndrome Detected by Optical Coherence Tomography
Authors: Joris Fuijkschot, Johannes R.M. Cruysberg, Michèl A.A.P. Willemsen, Jan E.E. Keunen, Thomas Theelen
Journal: Ophthalmology (2007)
Protein Digestion in Human Intestine as Reflected in Luminal, Mucosal, and Plasma Amino Acid Concentrations after Meals
Authors: Siamak A. Adibi, Donald W. Mercer
Journal: Journal of Clinical Investigation (1973)

Normal human volunteers were intubated with either aspiration tubes or a biopsy capsule placed in the small intestine. The subjects were then fed a test meal containing 50 g of purified bovine serum albumin which served as the model dietary protein. Electrophoretic analysis of intestinal fluids showed that for at least 4 h the fed albumin was detectable in jejunal and ileal fluids. On separate occasions, subjects were fed the same meal without the protein. No protein was detected in intestinal fluids when the protein-free meal was fed. After the protein-rich meal, total concentrations of measured free and peptide amino acids rose from 3.21 to 29.29, and 15.94 to 117.97 mumol/ml, respectively, (P values < 0.02) in the jejunum. Similarly, total concentrations of measured free and peptide amino acids rose from 5.45 to 19.74, and 13.59 to 65.39, respectively, (P values < 0.05) in the ileum. In contrast, concentrations of free and peptide amino acids in intestinal fluids did not increase after the protein-free meal. While intracellular concentrations of amino acids in the jejunal mucosa did not show significant changes, plasma concentrations of each individual free amino acid were increased after the protein-rich meal and were either decreased or unaltered after the protein-free meal. The amino acid composition of the fed protein was reflected in the increases in intraluminal and plasma concentrations of individual amino acids after the protein-rich meal. It is concluded that after the ingestion of a test meal containing a substantial amount of protein which is within the usual range of dietary intake; (a) the exogenous protein is the principal source of the increased free and peptide amino acids in the intraluminal contents and in the plasma; (b) there are greater amounts of amino acids present as small peptides than in the free form in the gut lumen; (c) the ingested protein can be recovered as late as 4 h both in the jejunum and in the ileum.
Deep-Brain Stimulation for Generalized Dystonia
Authors: Paul Greene
Journal: New England Journal of Medicine (2005)

Dystonia is characterized by twisting postures, tremor, and pain resulting from sustained muscle contractions. Idiopathic dystonia, in which dystonia is the only neurologic symptom, follows a very different course, depending on whether it starts in childhood or adult life. In the more common adult-onset dystonia, symptoms of idiopathic dystonia are usually restricted to a single region of the body, such as the neck, arm, or face (focal dystonia), or to a limited number of contiguous regions (segmental dystonia). Childhood-onset dystonia often spreads beyond one or two segments, involving one leg, the second leg or the trunk, and at least one . . .
The Use (and Misuse) of Urinary Sodium and Chloride Measurements
Authors: Richard A. Sherman
Journal: JAMA (1982)

MEASUREMENT of urinary sodium and chloride concentrations is useful whenever knowledge of whether the kidney is retaining salt will narrow the differential diagnosis. Any concentration of sodium or chloride in the urine is normal if it favors maintenance of normal systemic fluid and electrolyte status. Only when a patient's fluid and electrolyte status is abnormal and one can predict what a normal kidney's protective response would be can study of the urine electrolytes be of value.  Detection of a Salt-Retaining State  Urinary sodium and urinary chloride concentrations should both be determined whenever the concentration of one or the other electrolyte is sought. If the kidney is in a saltretaining state, both urinary sodium and chloride concentrations usually are less than 20 mEq/L. It is, however, not unusual for one or the other electrolyte level to be deceptively high due to the need for electroneutrality in the urine. For example, in
NEW YORK LETTER.
Authors: None Vindex
Journal: JAMA (1884)

<h3>To the Editor of the Journal of the American Medical Association:</h3><h3>Dear Sir:</h3> —I am under obligations to you for your editorial of Feb. 9. It confirms my statement, if any confirmation was needed, that the American Medical Association is in the grasp of a few men. Had the Medical Society of the State of New York attempted, through its delegates, to move to amend the Code of Ethics of the American Medical Association, the motion would, under ruling, have gone to the Judicial Council, and been disposed of, by your showing, without appeal. Such modes of action may secure, for long periods even, a simulation of peace and harmony, but volcanic eruption will surely, sooner or later, give vent to pent-up opinion. The question of the right of a State Society to change its by-laws or code of ethics, and to retain its place in the American Medical Association,
Lung Homotransplantation in Man
Authors: James D. Hardy, Watts R. Webb, Martin L. Dalton, George R. Walker
Journal: JAMA (1963)

THE TECHNICAL FEASIBILITY of lung replantation and homotransplantation in animals was established by the work of previous investigators.<sup>1, 2</sup>It was found that occasionally a dog could survive temporarily on the function of the lung homotransplant alone, especially if the respiratory reflexes from the unexcised lung had been preserved. Preservation of these reflexes with exclusion of pulmonary function in this "normal" or contralateral lung was achieved by ligation of the pulmonary artery on this side. In addition to studies demonstrating that either a reimplanted lung or a homotransplanted lung could function fairly effectively to provide a significant degree of pulmonary function, the use of various agents in dogs to suppress the immune response had permitted substantial prolongation of the survival of lung homografts. In our own experience, the lung homograft had been rejected in untreated dogs in an average of from seven to eight days, whereas in dogs
Early detection of myocardial reperfusion by assay of plasma MM-creatine kinase isoforms in dogs.
Authors: S R Devries, B E Sobel, D R Abendschein
Journal: Circulation (1986)

To determine whether myocardial reperfusion can be detected promptly by changes in profiles of isoforms of MM-creatine kinase (CK) in plasma, coronary occlusion was induced in 30 conscious dogs and reperfusion was initiated after 1, 2, 3, or 4 hr in 21. The myocardial isoform of MM-CK, MMA, was quantified in serial plasma samples by chromatofocusing. Before coronary occlusion, MMA comprised 13 +/- 7% (SD) of the total CK activity in plasma. The percentage of MMA (MMA%) was elevated before reperfusion, but increased markedly and consistently to a peak of 52 +/- 13% (n = 21) between 30 min and 1 hr after the time of onset of reperfusion. The rate of increase in MMA% was significantly faster with reperfusion at 1 hr (1.44 +/- 0.42% min-1), 2 hr (1.28 +/- 0.45% min-1), or 3 hr (1.02 +/- 0.27% min-1) (p less than .001), but not with reperfusion at 4 hr (0.48 +/- 0.34% min-1) compared with the rate in nonreperfused control dogs (0.29 +/- 0.09% min-1). Furthermore, the rate of increase in MMA% was neither influenced by peak total CK activity (r = -.1) nor dependent on infarct size measured histochemically 24 hr after coronary occlusion (r = -.003). The time from coronary occlusion to the peak of MMA% was reduced by reperfusion at 1 to 3 hr compared with control, but this index was not identified as rapidly as the rate of increase in MMA%. Accordingly, characterization of the rate of increase in MMA% in plasma when reperfusion occurs early after the onset of myocardial infarction permits prompt, reliable, and noninvasive detection of myocardial reperfusion.
Experimental acute pancreatitis in the rat--a new model.
Authors: U Chetty, H M Gilmour, T V Taylor
Journal: Gut (1980)

A new experimental model of acute pancreatitis in the rat has been devised. It consists of a closed duodenal loop into which infected bile is injected under pressure; intestinal continuity is maintained by a plastic tube passed through the loop. Histological and biochemical evidence of acute pancreatitis in the rat model is presented. The model has been compared with that of Nevalainen and with control groups of rats undergoing bile duct ligation and sham operation. The model produces a consistently fatal acute pancreatitis, more severe than that produced by Nevalainen9s model, with a survival time fo 28+/-12.8 (SD) hours. A combination of the reflux of infected bile under increased pressure into the pancreatic duct, at a known time, produces a model which may be suitable for the investigation of therapeutic agents.
USE OF STEEL PHONOGRAPH NEEDLE AS A RETAINING PIN IN CERTAIN IRREDUCIBLE FRACTURES OF THE SMALL BONES
Authors: C. E. Tennant
Journal: JAMA (1924)

The need for a small but easily applied pin for the retention of obstinate displaced fragments in small bone injuries, I have found to be very satisfactorily met by the use of the small phonograph needle. This needle is made of tough steel, with an exceedingly smooth, highly polished surface, and comes to a well tapered point which readily admits of pushing through the approximated bone segments by simply placing the needle in a good holder and pushing (not driving) it through the bone. This method assures the pin of firm seating, or transfixation, and it is seldom necessary to remove it, although placed in the presence of infected tissue, as in open fractures. These needles are applicable in oblique fractures about the hands, foot, patella and clavicle and other small bones, and in many instances may be pushed through the skin, making no more than a needle puncture. The
RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications
Authors: Mayte Suárez-Fariñas, Benjamin Ungar, Joel Correa da Rosa, David A. Ewald, Mariya Rozenblit, Juana Gonzalez, Hui Xu, Xiuzhong Zheng, Xiangyu Peng, Yeriel D. Estrada, Stacey R. Dillon, James G. Krueger, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2015)
Onset of NIDDM occurs at Least 4–7 yr Before Clinical Diagnosis
Authors: Maureen I Harris, Ronald Klein, Tim A Welborn, Matthew W Knuiman
Journal: Diabetes Care (1992)

Objective To investigate duration of the period between diabetes onset and its clinical diagnosis. Research Design and Methods Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. Results Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred ∼ 4–7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9–12 yr before its clinical diagnosis. Conclusions These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.
Abstract 4558: Resveratrol alters the kinase activity of PKG-Iα and Src family in A2780cp cells (ovarian cancer cell line with mutated p53) resulting in growth inhibition
Authors: Priyatham Gorjala, Janica C. Wong, Benjamin F.b Constantino, Mary G. Johlfs, Renee Coffman, Harry Rosenberg, Ronald Fiscus
Journal: Cancer Research (2014)

Abstract Epithelial ovarian cancer is a leading cause of death in gynecological cancer patients. One major hurdle in treating ovarian cancer is drug resistance to commonly-used chemotherapy like cisplatin. Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a natural polyphenol found in foods/drinks like grapes, berries, peanuts and red wine, can inhibit tumor growth. Our lab has previously shown that resveratrol down-regulates expression of protein kinase G type-I (PKG-I) in cancer cells, which correlated with decreased cell proliferation and increased apoptosis. For the present study, we used A2780cp cells, which are cisplatin-resistant epithelial ovarian cancer cells with mutated p53. Our data show that resveratrol did not induce apoptosis even at a higher concentration of 500 µM. However, resveratrol caused concentration-dependent decreases (down to 50% of control levels at 100 µM) of both DNA synthesis and cell adhesion. We also observed a concentration-dependent increase in protein expression levels of PKG-I to 3 times of control levels at 50 µM resveratrol, but a drop at 100 µM resveratrol. Though total Src remained fairly unchanged, pSrcY416 (phosphorylation at tyrosine-416) and pSrcS17 (phosphorylation at serine-17), indicators of Src activation, decreased at 50 and 100 µM resveratrol [assessed by ultrasensitive quantitative NanoPro 1000 (ProteinSimple), a new state-of-the-art capillary electrophoresis-based protein analysis system]. Decreased pSrcY416 levels (44% of control levels at 100 µM resveratrol) suggest that the kinase activity of Src family kinases are decreased at the higher concentrations of resveratrol that cause inhibition of ovarian cancer cell proliferation. These results suggest that resveratrol can be effective in decreasing cell proliferation in chemoresistant ovarian cancer cells and that the mechanism of action of resveratrol may involve a down-regulation of the protein expression levels of PKG-I and the typrosine-kinase activity of Src family of kinases. Citation Format: Priyatham Gorjala, Janica C. Wong, Benjamin F.b Constantino, Mary G. Johlfs, Renee Coffman, Harry Rosenberg, Ronald Fiscus. Resveratrol alters the kinase activity of PKG-Iα and Src family in A2780cp cells (ovarian cancer cell line with mutated p53) resulting in growth inhibition. [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 4558. doi:10.1158/1538-7445.AM2014-4558
Indian association questions plan for hepatitis B immunisation
Authors: Ganapati Mudur
Journal: BMJ (2006)

The Indian Medical Association has criticised a government proposal to expand universal immunisation against the hepatitis B virus throughout India, saying that it would be “wasteful spending” on a low priority health problem.

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The Indian Medical Association says vaccinating babies against hepatitis B is wasteful as carrier status is often transmitted vertically

Credit: P VIROT/WHO

In a report sent to the health ministry, the association said that a systematic review of studies indicates that the rate of chronic carriage of hepatitis B in India is 1.6% and not 4% as projected. …

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Brain Infarction and the Clinical Expression of Alzheimer Disease-Reply
Authors: David A. Snowdon
Journal: JAMA (1997)

In Reply.  —The analyses of Drs Mirra and Gearing indicate that brain infarcts are not associated with NFTs in the neocortex. Our analyses also indicated that brain infarcts were not associated with the number of NFTs, senile plaques, or neuritic plaques in the neocortex, suggesting that AD lesions and brain infarcts were likely to have occured independently of each other.  While AD and brain infarction may represent separate disease processes, their combination may nonetheless increase the likelihood that dementia will occur. Among the participants in our study who met our neuropathologic criteria for AD (ie, abundant senile plaques and some NFTs in the neocortex), those with 1 or 2 lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without brain infarcts. The prevalence of dementia was 93% for those with such subcortical lacunar infarcts and 57% in those without infarcts.
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Authors: Struan F A Grant, Gudmar Thorleifsson, Inga Reynisdottir, Rafn Benediktsson, Andrei Manolescu, Jesus Sainz, Agnar Helgason, Hreinn Stefansson, Valur Emilsson, Anna Helgadottir, Unnur Styrkarsdottir, Kristinn P Magnusson, G Bragi Walters, Ebba Palsdottir, Thorbjorg Jonsdottir, Thorunn Gudmundsdottir, Arnaldur Gylfason, Jona Saemundsdottir, Robert L Wilensky, Muredach P Reilly, Daniel J Rader, Yu Bagger, Claus Christiansen, Vilmundur Gudnason, Gunnar Sigurdsson, Unnur Thorsteinsdottir, Jeffrey R Gulcher, Augustine Kong, Kari Stefansson
Journal: Nature Genetics (2006)
EUS-FNA and EBUS-TBNA; the pulmonologist’s and surgeon's perspective
Authors: M. Krasnik, P. Vilmann, F. Herth
Journal: Endoscopy (2006)

Lung cancer is the leading cancer related cause of death in the western world [1]. The prognosis is directly related to the stage of the disease. Treatment strategies are largely based on the cell type of the tumor, i. e. either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), and the presence of mediastinal involvement or distant spread of the tumor [1] [2]. The treatment of SCLC is mainly chemotherapy whereas NSCLC treatment is fully stage dependent ranging from surgery only to down-staging chemotherapy with subsequent surgery or entirely experimental chemotherapy/radiotherapy.
Recognition of Leukaemia Cells as Foreign before and after Autoimmunization
Authors: R. L. Powles, L. A. Balchin, G. H. Fairley, P. Alexander
Journal: BMJ (1971)

Leukaemia cells in the peripheral blood of nine patients with acute leukaemia were removed and stored. When the patients had been brought into haematological remission these leukaemia cells were cultured with autologous lymphocytes both before and after the patients had been autoimmunized with their own irradiated leukaemia cells. The extent to which the leukaemia cells stimulated the "normal lymphocytes" was increased as the result of autoimmunization.The implications of the use of this test for determining the best regimen for "immunotherapy" in acute leukaemia are discussed.