tbuckley/cabot-search huggingface dataset:
Abstract 1242: Induction and targeting of polyploid senescent cells in cancer therapeutics
Authors: Qin Wang, Peter Wu, Iana Ivanova, Elizabeth Chu, Daniel Y. Wu
Journal: Cancer Research (2011)

Abstract Therapy-induced cellular senescence (TCS), an emerging concept in cancer therapeutics, describes an in vivo response of human tumors to chemotherapy and radiation. These treatments elicit a coordinated response that results in prolonged cell cycle arrest, characteristic senescence morphology and expression of senescence-specific markers. In the past decade, a growing body of evidence has supported the hypothesis that “senescence response occurs in treated human cancers and the response is reversible.” We now present evidence that TCS may be adverse to cancer therapeutics based on a clinicopatholgical study conducted in patients with advanced non-small cell lung cancer following induction therapy prior to surgery. To further define how a subpopulation of senescent cells could escape terminal arrest, our work now implicates a polyploid state through which senescent cells can survive and eventually resume proliferation. In H1299 lung cancer cells, we show that mitotic kinase Cdk1 facilitates endoreplication and formation of polyplid senescent cells (PSCs) following chemotherapy as the genetic modulation of Cdk1 activity profoundly affect the prevalence of these polyploid cells. Importantly, senescence escape occurs from the PSCs at 2.5 times the frequency of escape observed from diploid (2/4n) cells through novel non-canonical cell division mechanisms. Furthermore, we also demonstrate distinct functions of p21 and p27, two members of KIP family in TCS. While both interact with endogenous cyclin B1-Cdk1 complex in senescent cells, only p27 directly inhibits Cdk1 kinase activity and modulates PSC formation, whereas the knockdown of p21 leads to massive apoptosis. Finally, we show that statins, HMG-CoA inhibitors, currently approved for treatment of dyslipidemia down-regulate several key targets of the Cdk1 pathway, including Cdk1 itself, cyclin B1, and survivin, while up-regulating p27. Statins both decrease polyploid cells and abrogate escape of several cancer cell lines from TCS. Altogether, our work here challenges the current cancer treatment paradigm and supports the incorporation of novel strategies to enforce irreversible cell cycle exit in senescent tumor cells following treatment. 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 1242. doi:10.1158/1538-7445.AM2011-1242
Tennis Balls and Eye Injuries
Authors: Norman J. Holter
Journal: JAMA (1977)

To the Editor.—  Dr Seelenfreund replies to a letter from Dr Duke regarding tennis ball injuries to the eye (236:2287, 1976) and recommends impact-resistant glasses, among other things.  I would like to report a reason to object to such glasses and to recommend use of only some physical device surrounding the bony orbit. I was struck in the lens of such glasses, which in turn became the very hard missile that fit inside of my bony protection and struck the eyeball. This produced a shock wave to the retina, with some loss of eyesight still remaining after several years. The frame of these glasses was a total loss. Offhand, I would think a blow by a softer object—the ball—would be preferable to being struck by a very hard object—the hard glass lens. I opt for the handball steel protector in spite of some interference with vision.
1398 BRIVANIB VERSUS PLACEBO IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA (HCC) WHO FAILED OR WERE INTOLERANT TO SORAFENIB: RESULTS FROM THE PHASE 3 BRISK-PS STUDY
Authors: J.M. Llovet, T. Decaens, J.-L. Raoul, E. Boucher, M. Kudo, C. Chang, Y.-K. Kang, E. Assenat, H.-Y. Lim, V. Boige, P. Mathurin, L. Fartoux, D.-Y. Lin, J. Bruix, R.T. Poon, M. Sherman, J.-F. Blanc, R. Finn, W.-Y. Tak, Y. Chao, R. Ezzeddine, D. Liu, I. Walters, J.-W. Park
Journal: Journal of Hepatology (2012)
Radiation associated malignant pleural mesothelioma.
Authors: Y Lerman, Y Learman, P Schachter, E Herceg, Y Lieberman, A Yellin
Journal: Thorax (1991)

Malignant pleural mesothelioma of epithelial type developed in a 24 year old woman, 20 years after radiotherapy for Hodgkin's disease. This case and a review of published cases indicate that radiation may induce malignant mesothelioma.
Effects of unilateral renal arterial constriction on tubular reabsorption of sodium and water during an osmotic diuresis.
Authors: R M Stein, R G Abramson, D D Bercovitch, M F Levitt
Journal: Journal of Clinical Investigation (1965)

Previous studies have indicated that acute re- ductions in glomerular filtration rate (GFR), during loading with nonreabsorbable solute, in- crease the fraction of the filtered sodium load reabsorbed (1-3).The renal tubular sites at which this enhanced reabsorption develops have not been elucidated.Recent studies from this laboratory in which mannitol loads were adminis- tered to salt-depleted subjects with modest reduc- tions in GFR suggested that sodium reabsorption was enhanced within the proximal tubule (4).However, it was not possible to determine whether renal hemodynamics or other, perhaps hormonal, factors were responsible for the increased reab- sorption at this site.The present studies were designed to evaluate the specific effects of a re- duction in GFR produced by renal arterial con- striction on tubular sodium reabsorption.We propose that renal arterial constriction during load- ing with nonreabsorbable solute provokes an en- hanced reabsorption of sodium, in large part within the proximal tubule. MethodsExperiments were performed in seven hydrated and eight hydropenic female mongrel dogs (17 to 24 kg), anes- thetized with ethyl carbamate and a-chloralose administered intravenously.After appropriate priming doses of inulin and para-aminohippurate (PAH), a sustaining solution containing a sufficient amount of inulin and PAH *
Hyperglycaemic effect of nifedipine.
Authors: S Charles, J M Ketelslegers, M Buysschaert, A E Lambert
Journal: BMJ (1981)

histotoxic symptoms may be due to these, but the exact mechanism of action of thiocyanates is not known.4Thiocyanate intoxication with blood concentrations above 200 mg/l may be rapidly corrected by haemodialysis, which reportedly removes several grams of the drug.5We tried peritoneal dialysis but in the absence of clearance studies, which we could not do, we cannot comment on the procedure for intoxication with this compound.Distal part of oesophagus and stomach showing necrotic mucosa.
Massive Calcification in Pseudohypoparathyroidism
Authors: Tominaga Shimizu, Teiji Takeda
Journal: New England Journal of Medicine (2003)

A 55-year-old man with a 24-year history of pseudohypoparathyroidism type 2 presented with a mass in the right buttock and reported difficulty walking. At the time of diagnosis, he had had a low serum calcium level (5.2 mg per deciliter [1.3 mmol per liter]) and a high phosphate level (9.1 mg per deciliter [2.9 mmol per liter]) without an increase in urinary phosphate excretion despite normal urinary excretion of cyclic adenosine monophosphate in response to parathyroid hormone. At that time, he was treated with vitamin D, aluminum gel, and calcium carbonate. Subsequently, serum calcium and phosphate levels were well controlled, . . .
Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver
Authors: Nobuyuki Morikawa, Makoto Suematsu, Takanori Kyokane, Nobuhito Goda, Yusuke Kumamoto, Taro Okitsu, Yuzuru Ishimura, Masaki Kitajima
Journal: Hepatology (1998)

Although discontinuous total parenteral nutrition (d–TPN) has recently been favored for clinical use over continuous total parenteral nutrition (c–TPN) to ameliorate liver dysfunction, mechanisms for the protection against postoperative liver dysfunction remain unknown. This study aimed to examine differences in mitochondrial function in d–TPN– and c–TPN-pretreated livers during ischemia–reperfusion. Rat livers pretreated with d–TPN or c–TPN were perfused with Krebs–Ringer buffer and were exposed to 25% low–flow hypoxia followed by reperfusion. Intrahepatic mitochondrial membrane potential (△Ψ) and cell viability were assessed by dual–color digital microfluorography using rhodamine 123 (Rh123) and propidium iodide (PI), respectively. In response to hypoxia, livers pretreated with c–TPN, d–TPN, and an ordinary chow diet exhibited a significant △Ψ reduction among the entire lobules. Upon reperfusion, the regional △Ψ values further decreased in the c–TPN liver, whereas those in the d–TPN-treated or chow–treated livers displayed a rapid recovery toward the control levels. The severity of cell injury did not differ among the groups, showing that the reperfusion–induced △Ψ drop in the c–TPN-pretreated liver is not a consequence of cell injury. Differences in the △Ψ drop among the groups appear to occur irrespective of those in the glycogen storage, because the livers undergoing d–TPN display a marked △Ψ recovery even when reperfused at the end of a fasted state. These results indicate that c–TPN, but not d–TPN, jeopardizes mitochondrial re–energization and suggest that a circadian pattern of the TPN serves as a potentially beneficial strategy to reduce the risk of postischemic mitochondrial dysfunction in the liver.
Parasystole with Fixed Coupling
Authors: RICHARD LANGENDORF, ALFRED PICK
Journal: Circulation (1967)

Four examples of spontaneous and six of artificial ventricular parasystole exhibiting fixed coupling of the premature beats were presented. In five cases, one of the pacemakers was located in the S-A node, in four in the A-V junction, and in one at first in the A-V junction and later in the ventricles. The material was divided according to the presence either of mutual protection of the two pacemakers (group I, four cases) or of unilateral protection of the parasystolic pacemaker (group II, five cases). When the rates of both pacemakers are regular and the conditions for impulse propagation remain stable, fixed (forced) coupling of parasystolic beats develops under the following conditions: in group I (with mutual protection) (a) if there is-by chance or by experimental adjustment-a simple numerical relation between the two pacemaker rates, or (b) if subthreshold stimuli become effective only during a short super-normal period of excitability in the early portion of the ventricular cycle; and in group II (with unilateral protection) as a result of a fixed relationship that develops secondarily to the discharge of the dominant pacemaker by the parasystolic pacemaker, a mechanism referred to as "reversed coupling." This mechanism may be combined with that of group Ib.
Reconstituted High-Density Lipoprotein Inhibits Thrombin-Induced Endothelial Tissue Factor Expression Through Inhibition of RhoA and Stimulation of Phosphatidylinositol 3-Kinase but not Akt/Endothelial Nitric Oxide Synthase
Authors: Hema Viswambharan, Xiu-Fen Ming, Shengsi Zhu, Alphonse Hubsch, Peter Lerch, Guy Vergères, Sandro Rusconi, Zhihong Yang
Journal: Circulation Research (2004)

Endothelial cells express negligible amounts of tissue factor (TF) that can be induced by thrombin, which is important for acute coronary syndromes. Recent research suggests that endothelial TF expression is positively regulated by RhoA and p38mapk, but negatively by Akt/endothelial nitric oxide synthase (eNOS) pathway. High-density lipoprotein (HDL) is atheroprotective and exerts antiatherothrombotic effect. This study investigated the effect of a reconstituted HDL (rHDL) on endothelial TF expression induced by thrombin and the underlying mechanisms. In cultured human umbilical vein and aortic endothelial cells, thrombin (4 U/mL, 4 hours) increased TF protein level, which was reduced by rHDL (0.1 mg/mL, 43% inhibition, n=3 to 7, P<0.01). Activation of RhoA but not p38mapk by thrombin was prevented by rHDL. rHDL stimulated Akt/eNOS pathway. The phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY294002 abolished the activation of Akt/eNOS and reversed the inhibitory effect of rHDL on TF expression. Adenoviral expression of the active PI3K mutant (p110) reduced TF expression stimulated by thrombin without inhibiting RhoA activation, whereas expression of the active Akt mutant (m/p) further facilitated TF upregulation by thrombin. Moreover, a dominant-negative Akt mutant (KA) reduced thrombin's effect and did not reverse the rHDL's inhibitory effect on TF expression. Inhibition of eNOS by N(omega)-nitro-L-arginine methyl ester (100 micromol/L) did not affect the rHDL's effect. In conclusion, rHDL inhibits thrombin-induced human endothelial TF expression through inhibition of RhoA and activation of PI3K but not Akt/eNOS. These findings implicate a novel mechanism of antiatherothrombotic effects of HDL.
Extraspinal Tendon and Ligament Calcification Associated with Long-Term Therapy with Etretinate
Authors: John J. DiGiovanna, Roberta K. Helfgott, Lynn H. Gerber, Gary L. Peck
Journal: New England Journal of Medicine (1986)

Isotretinoin, a synthetic retinoid that has been prescribed for over 500,000 patients with cystic acne, has been associated with both spinal hyperostosis and a disorder similar to diffuse idiopathic skeletal hyperostosis. We describe a syndrome of tendon and ligament calcification, primarily in extraspinal locations, that we have observed after long-term therapy for psoriasis and disorders of keratinization with etretinate, another synthetic retinoid. Of 38 patients who had received etretinate (average dose, 0.8 mg per kilogram of body weight per day; average duration, 60 months), 32 (84 percent) had radiographic evidence of extraspinal tendon and ligament calcification. The most common sites of involvement were the ankles (29 patients [76 percent]), pelvis (20 patients [53 percent]), and knees (16 patients [42 percent]); spine involvement was uncommon in this group of etretinate-treated patients. Involvement tended to be bilateral and multifocal. Fifteen (47 percent) of the 32 affected patients had no bone or joint symptoms at the sites of radiographic abnormality. Thus, tendon and ligament calcification can occur without vertebral involvement as well as in association with it (for example, as part of the spectrum of diffuse idiopathic skeletal hyperostosis). We have identified extraspinal tendon and ligament calcification as a toxic effect that is commonly associated with long-term etretinate therapy.
Glomerular filtration rate in schoolgirls with covert bacteriuria.
Authors: J Guillet, B Basse-Cathalinat, E Christophe, S Wynchank, P Blanquet
Journal: BMJ (1983)

A consistent approach using standardised items to assess e-cigarette use in both youth and adult populations will aid cross-survey and cross-national comparisons of the effect of e-cigarette (and tobacco) policies and improve our understanding of the population health impact of e-cigarette use. Focusing on adult behaviour, we propose a set of e-cigarette use items, discuss their utility and potential adaptation, and highlight e-cigarette constructs that researchers should avoid without further item development. Reliable and valid items will strengthen the emerging science and inform knowledge synthesis for policy-making. Building on informal discussions at a series of international meetings of 65 experts from 15 countries, the authors provide recommendations for assessing e-cigarette use behaviour, relative perceived harm, device type, presence of nicotine, flavours and reasons for use. We recommend items assessing eight core constructs: e-cigarette ever use, frequency of use and former daily use; relative perceived harm; device type; primary flavour preference; presence of nicotine; and primary reason for use. These items should be standardised or minimally adapted for the policy context and target population. Researchers should be prepared to update items as e-cigarette device characteristics change. A minimum set of e-cigarette items is proposed to encourage consensus around items to allow for cross-survey and cross-jurisdictional comparisons of e-cigarette use behaviour. These proposed items are a starting point. We recognise room for continued improvement, and welcome input from e-cigarette users and scientific colleagues.
Abstract 3676: Selective modulation of CHOP/GADD153 in prostate cancer cells by alpha-mangostin promotes cell death.
Authors: Gongbo Li, Sakina Petiwala, Dana Pierce, Jeremy Johnson
Journal: Cancer Research (2013)

Abstract Background: It is well-established that during endoplasmic reticulum (ER) stress cells utilize several cell signal pathways collectively named “unfolded protein reaction (UPR)” to re-establish homeostasis and promote cell survival. The upregulation of UPR proteins to an extent is thought to be a growth advantage for cancer cells. However, chronic ER stress or prolonged UPR will lead to apoptosis. Alpha-mangostin, a xanthone from mangosteen fruit, has been reported to effectively induce prostate cancer cell apoptosis in vitro and suppress xenograft tumor growth. Thus, we investigated the alteration of ER stress-related proteins in mangosteen fruit extract (MFE)- or α-Mangostin-treated prostate cancer cells as well as its correlation with apoptosis. Methods: Two human prostate cancer cell lines, 22Rv1 and LNCaP, and a prostate epithelial cell line were treated with MFE or α-mangostin. Flow cytometry, MTT and BrdU were used to evaluate cell apoptosis, viability and proliferation. Western blot and fluorescent microscopy were used to detect proteins involved in apoptosis or ER stress. We also evaluated the anti-cancer activity of MFE and α-mangostin in nude mice inoculated with 22Rv1 cells. In addition, pharmacokinetics data of α-mangostin was collected on wild type C57BL6 mice for toxicity concern. Results: MFE increased apoptosis, decreased viability and inhibited proliferation in prostate cancer cell lines. Both MFE and α-mangostin significantly upregulated the expression of ER stress proteins, such as PERK, CHOP and IRE1α. Both MFE and α-mangostin also effectively suppressed tumor growth in a xenograft tumor model without affecting body weight. Interestingly, CHOP knockdown enhanced apoptosis in α-mangostin-treated prostate cancer cells; both MFE and α-mangostin decreased PERK expression and did not induce ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. Conclusions: Both MFE and α-mangostin selectively promote ER stress in prostate cancer cells and inhibit prostate cancer cell growth in a xenograft mouse model without observable toxicity, suggesting further research is needed to evaluate its potential as an anti-cancer agent. Citation Format: Gongbo Li, Sakina Petiwala, Dana Pierce, Jeremy Johnson. Selective modulation of CHOP/GADD153 in prostate cancer cells by alpha-mangostin promotes cell death. [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 3676. doi:10.1158/1538-7445.AM2013-3676
The Relationship between Neutrophil to Lymphocyte Ratio and Isolated Coronary Artery Ectasia
Authors: Mehmet Doğan, Tolga Çimen, Murat Bilgin, Uğur Arslantaş, Haci Ahmet Kasapkara, Sadık Açıkel, Ekrem Yeter
Journal: Journal of the American College of Cardiology (2013)
Uninsured people get poor deal from organ donation in the US
Authors: J. Lenzer
Journal: BMJ (2008)

A study of US organ donors and recipients shows a “dirty little secret” of solid organ transplantation: transplant donors are far more likely to be uninsured than are the recipients, according to the coauthor Steffie Woolhandler, associate professor of medicine at Harvard Medical School ( International Journal of Health Services 2008;38:641-52).

The researchers examined the insurance status of 1447 organ donors, both live donors and cadaveric donors, and 4962 transplant recipients from the national inpatient sample database, which provides a nationally representative sample of all US hospital stays.

They found that 16.9% of the donors were uninsured compared to 4.6% of other hospital inpatients, whereas only 0.8% of the recipients were uninsured.

The finding that most transplant recipients were insured at the time of their transplant had …
Suggestions for the Treatment of Special Cases of Empyema by Thoracentesis and the Simultaneous Injection of Purified Air
Authors: R. W. Parker
Journal: BMJ (1883)

aged three and three- quarter years, was admitted into the East London Hospital for Children, under the care of my colleague, Dr. H. Donkin, with ob- vious signs of a large pleuritic effusion in the left chest, following an attack of scarlatinal nephritis; the heart was beating to the right of the right nipple.She was aspirated with a Potain's aspirator, but only three and a half ounces of pus (which was quite sweet) could be withdrawn.The needle was introduced a little below the angle of the scapula.There was but little alteration in the physical signs.During the next few days she lay on her left side, and had much distress in her breathing.A tracing taken with the cyrtometer at this time showed an increase in the size of the chest, and in its shape also, which approached to that of a circle.I
Heredity and Cancer Control: Genetic Counseling.
Authors: Henry T. Lynch
Journal: Annals of Internal Medicine (1967)

s1 May 1967Heredity and Cancer Control: Genetic Counseling.Henry T. Lynch, M.D., David E. Anderson, Ph.D., Anne J. Krush, M.S.Henry T. Lynch, M.D.Search for more papers by this author, David E. Anderson, Ph.D.Search for more papers by this author, Anne J. Krush, M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1065_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptApproximately 250,000 deaths from cancer occur annually in the United States. Of these, an estimated 80,000 lives could be salvaged by earlier cancer detection. Hereditary forms of malignancies undoubtedly were present in a significant proportion of these patients. Had genetic knowledge for the predictability of malignancies in families been applied, many of these patients could have been offered a better prognosis. Such malignancies as Gardner's syndrome, retinoblastoma, familial polyposis coli, xeroderma pigmentosum, nevoid basal cell carcinoma syndrome, and neurofibromatosis show classic mendelian inheritance while others, including carcinoma of the breast, stomach, lung, and prostate, show a hereditary predisposition posing a... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Houston, Texas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1065-1066KeywordsBasal cell carcinomasCancer geneticsGenetic counselingGeneticsHeredityLung and intrathoracic tumorsStomach Issue Published: 1 May 1967 PDF downloadLoading ...