tbuckley/cabot-search huggingface dataset:
Abstract 1719: Differential Mcl-1 processing in evasion of DCA-induced apoptosis of colorectal cancer cells.
Authors: Leanne M. Delaney, Brenda L. Coomber
Journal: Cancer Research (2013)

Abstract Recent evidence indicates that dichloroacetate (DCA) may be a cancer-specific agent that targets the unique metabolism of cancer cells, avoiding disruption of normal somatic cells. However, our laboratory has shown that some human colorectal cancer cell lines do not show the predicted response to DCA treatment, and the molecular mechanism responsible for this is currently unknown. Of interest is the Bcl-2 protein family, which consists of both pro- and anti-apoptotic members. The expression, regulation, and interactions of the Bcl-2 proteins will mediate the release of cytotoxic molecules such as cytochrome c from the mitochondria into the cytosol, activating apoptosis via a caspase cascade. Differential regulation of the Bcl-2 proteins in response to DCA treatment may indicate whether apoptosis will be induced in cancer cell lines. The human colorectal cancer cell line HCT116 was cultured and exposed to DCA as well as 5-fluorouracil, a known initiator of Bcl-2 protein-mediated apoptosis. Key changes in Bcl-2 protein expression were analyzed using immunoblotting. The expression of Mcl-1, an anti-apoptotic Bcl-2 protein, occurred at 40-kDa in all treatments, and at 28-kDa only in non-DCA treatments. PCR for the known splice variants of Mcl-1 confirmed only one gene product, suggesting the involvement of post-translational modification. The presence of cleaved caspase 3 indicates that an increase in 28-kDa Mcl-1 compared to 40-kDa Mcl-1 occurs with apoptosis in 5-fluorouracil treated cells, but does not occur in DCA-treated cells, which were not apoptotic. This suggests that Mcl-1 modification may be acting to modulate susceptibility to DCA treatment. The interactions involved in or resulting from these responses are currently under investigation. Using modified HCT116 cells without functional p53 or without functional Bax, the role of these two proteins will be emphasized. Co-immunoprecipitation of Mcl-1 will allow changes in its binding partners, such as p53, to be observed in response to DCA treatment. By utilizing mitochondrial and cytosolic fractions for protein analysis, the effect of DCA on mitochondrial localization of proteins such as Bax and the release of cytochrome c from the mitochondria will be observed. Further research may provide insight into the mechanism by which some human cancer cell lines are protected against DCA-induced cell death, and the potential role of a pathway involving Mcl-1 in this cell-specific protection. Citation Format: Leanne M. Delaney, Brenda L. Coomber. Differential Mcl-1 processing in evasion of DCA-induced apoptosis of colorectal cancer cells. [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 1719. doi:10.1158/1538-7445.AM2013-1719
Functional maturation of human pluripotent stem cell derived cardiomyocytes in vitro – Correlation between contraction force and electrophysiology
Authors: Marcelo C. Ribeiro, Leon G. Tertoolen, Juan A. Guadix, Milena Bellin, Georgios Kosmidis, Cristina D'Aniello, Jantine Monshouwer-Kloots, Marie-Jose Goumans, Yu-li Wang, Adam W. Feinberg, Christine L. Mummery, Robert Passier
Journal: Biomaterials (2015)
Long-term effects of distal splenorenal shunt on hepatic hemodynamics and liver function in patients with cirrhosis: Importance of reversal of portal blood flow
Authors: Antonio M. Lacy, Miguel Navasa, Rosa Gilabert, Concepción Brü, Juan C. García-Pagán, Juan C. García-Valdecasas, Luis Grande, Fausto Feu, José Fuster, José Terés, José Visa, Jaime Bosch
Journal: Hepatology (1992)

We studied 23 patients with cirrhosis who had undergone retroperitoneal distal splenorenal shunt without portal-azygos disconnection more than 2 yr earlier. We investigated the suitability of the Doppler technique (ultrasound + Doppler) to assess the patency and blood flow direction through the portal vein and the distal splenorenal shunt and its correlation with the continuous thermal dilution technique. The study also assessed the influence of the distal splenorenal shunt and time after surgery on portal perfusion and liver function. Ultrasound + Doppler distal splenorenal shunt thrombosis in two patients; however, none was confirmed by continuous thermal dilution. Ultrasound + Doppler flowmetry was possible in 19 patients (83%) (mean, 1.58 +/- 0.53 L/min). Distal splenorenal shunt continuous thermal dilution measurements were performed in all patients (100%), (mean, 1.65 +/- 0.5 L/min). Good correlation was seen between them (r = 0.66). Ultrasound + Doppler of the portal vein showed a hepatopetal flow in 16 patients (69.9%). Hepatic blood flow was significantly higher in patients with hepatopetal flow (p = 0.003). Hepatic clearance and intrinsic hepatic clearance of indocyanine green were significantly lower in patients with hepatofugal flow. Patients with hepatofugal flow had a higher incidence of chronic encephalopathy. None of the patients with a follow-up of less than 4 yr exhibited hepatofugal flow, whereas 7 of the 16 patients with a longer follow-up had hepatofugal flow (43.7%). The difference was statistically significant (p = 0.04). This study suggests that ultrasound + Doppler sonography may provide useful data in the evaluation of the patency and blood flow direction through the portal vein and the distal splenorenal shunt.(ABSTRACT TRUNCATED AT 250 WORDS)
Health status and health‐related quality of life associated with hemophilia
Authors: Ronald D. Barr, Mahassen Saleh, William Furlong, John Horsman, Julia Sek, Mohan Pai, Irwin Walker
Journal: American Journal of Hematology (2002)

Abstract The hemophilias are a group of disorders associated with a chronic burden of morbidity and early mortality. Improvements in these adverse features have been achieved by the use of clotting factor concentrates within comprehensive centers of specialized care providing home infusion programs. Offsetting effects from transfusion‐transmitted hepatitis and HIV infection are in recent decline. The net impact of these changes merits assessment. To test the a priori hypotheses that increasing severity of factor VIII deficiency would be associated with an increasing burden or morbidity and that hepatitis and HIV positivity would impair health status further, a cross‐sectional study of a population‐based cohort was undertaken in a regional hemophilia program in Ontario, Canada. A survey was made of mild, moderate, and severe hemophiliacs over 13 years of age who self‐reported their health status using a standard 15‐item questionnaire. The responses were converted to levels in the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems to form multi‐element vectors from which single‐attribute morbidity and overall health‐related quality of life utility scores were determined. The burden of morbidity was greater in hemophiliacs than in the general population and correlated with the category of disease (mild &lt; moderate &lt; severe). Hepatitis and HIV positivity conferred additional burdens of morbidity, which were mainly in the attributes of mobility (HUI2), ambulation (HUI3), and pain (HUI2/3), all of these differences reaching levels of statistical significance. Despite demonstrable improvements in the safety, effectiveness, and utilization of clotting factor concentrates, hemophiliacs continue to experience an important burden of morbidity. Measurement of this burden, as reported here, provides a basis for future economic evaluation of the costs and consequences of health care interventions provided to this population. Am. J. Hematol. 71:152–160, 2002. © 2002 Wiley‐Liss, Inc.
NF-κB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes
Authors: Nithya Mariappan, Carrie M. Elks, Srinivas Sriramula, Anuradha Guggilam, Zhizhen Liu, Olga Borkhsenious, Joseph Francis
Journal: Cardiovascular Research (2009)

Inflammatory molecules and their transcription factor, nuclear factor kappa-B (NF-κB), are thought to play important roles in diabetes-induced cardiac dysfunction. Here, we investigated the effects of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, in diabetic mice. Obese db/db mice and heterozygous lean mice (n = 8) were allowed free access to drinking water (control) or water containing PDTC (100 mg/kg) for 20 weeks. Left ventricular (LV) function was measured using echocardiography at baseline and at study end. Mice were sacrificed and LV removed for gene expression, biochemical, immunofluorescence, and mitochondrial assays. LV and mitochondrial reactive oxygen species (ROS), superoxide and peroxynitrite were measured using electron spin resonance spectroscopy. Enhanced NF-κB activity in db/db mice was associated with increased oxidative stress as demonstrated by increased ROS, superoxide, and peroxynitrite production, and increased NF-κB, gp91phox, and Nox1 expression; PDTC ameliorated these effects. Mitochondrial free radical production and structural damage were higher in the db/db group than in the control, db/db PDTC, and PDTC-treated heterozygous animal groups. This study demonstrates that NF-κB blockade with PDTC mitigates oxidative stress and improves mitochondrial structural integrity directly, through down-regulation of increased oxygen-free radicals, thereby increasing ATP synthesis and thus restoring cardiac function in type II diabetes.
Abstract 2350: Inhibition of Gli1 as a novel therapeutic target for lung squamous cell carcinoma
Authors: Chunli Shao
Journal: Cancer Research (2014)

Abstract Purpose: It is clear that Hedgehog (Hh) signaling pathway can promote small cell lung cancer development but is not sufficient to drive tumor formation. However, the functional role of Hh pathway in non-small cell lung cancer remains unclear. We found that Gli1, a transcription factor of Hh pathway, is highly expressed in lung squamous cell carcinoma (SSC). The purpose of our study is to identify the functional importance of Gli1 in lung SCC. Methods: We performed a genome-wide gene expression analysis to examine Hh pathway component expression in 275 lung cancer patient specimens. qRT-PCR and western blot were used to validate their expression in SCC lines. To further explore its biological function in lung SCC we manipulated Gli1 expression genetically or pharmacologically followed by colony formation and tumor formation assays. Results: Microarray analysis revealed that Gli1, Gli2, Gli3, and Smoothened are significantly upregulated in lung SCC compared to lung adenocarcinoma (AD). Consistently we found the increased expression of Glis in lung SCC lines relative to AD lines by real-time PCR and western blot. Knocking down Gli1 by siRNA decreased liquid colony formation ability and Gli1-luciferase reporter activity in SCC lines. A significant reduction of cell proliferation and liquid colony formation was observed in shGli1 expressing SCC cells compared to control cells. Gli1 specific inhibitor GANT61 strongly inhibited SCC cell proliferation through inducing cell apoptosis. However, Gli1 expression or transcriptional activity is not regulated by classical Hh pathway upstream regulators in lung SCC. We found that blocking PI3K or ERK pathways by pharmacological inhibitors significantly reduced Gli1 expression and cell survival. In addition, TGF-β stimulation promoted Gli1 expression and transcriptional activity in SCC cells. Conclusions: Our data suggest that Hh pathway downstream factor Gli1 expression is essential for cell proliferation and colony formation in lung SCC. Gli1 is not regulated by canonical Hh pathway regulators, whereas PI3K, ERK, and TGF pathways are involved in its regulation. Blocking Gli1 function is a novel therapeutic strategy for lung SCC treatment. Citation Format: Chunli Shao. Inhibition of Gli1 as a novel therapeutic target for lung squamous cell carcinoma. [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 2350. doi:10.1158/1538-7445.AM2014-2350
XDR-TB in South Africa: Revised Definition
Authors: Timothy H Holtz
Journal: PLoS Medicine (2007)

It is only about 25 years since the abolition or abandonment of TB sanatoria in South Africa.It is likely that there are people in South Africa who are familiar with the idea of isolation of TB patients from the general public emanating from the era of TB sanatoria, and it is conceivable that they are likely to be understanding of the reasons that were used to keep patients there during their treatment.These people could help to make the idea of isolation in sanatoria acceptable again to the general public.Anyway, the TB sanatoria of this era were rightfully regarded as hospitals, as indeed they were, and I cannot see why modern day sanatoria should be viewed any differently.Granted, with the likelihood that the patients detained in these envisaged isolation areas may be more likely to die than be discharged, it will be a mammoth task to convince the "detainees" to stay there or their families to allow them to be kept there, especially if they are minors or the elderly infi rm.It is a tough call but it is worth a try.
Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis
Authors: Yasuhiko Kimura, Carlo Selmi, Patrick S. C. Leung, Tin K. Mao, Joseph Schauer, Mitchell Watnik, Shigeki Kuriyama, Mikio Nishioka, Aftab A. Ansari, Ross L. Coppel, Pietro Invernizzi, Mauro Podda, Eric M. Gershwin
Journal: Hepatology (2004)

Epidemiological data suggest that environmental factors may trigger autoimmunity in genetically susceptible individuals. In primary biliary cirrhosis (PBC), it has been postulated that halogenated xenobiotics can modify self-molecules, facilitating the breakdown of tolerance to mitochondrial antigens. The transport and metabolism of xenobiotics is highly dependent on key genetic polymorphisms that alter enzymatic phenotype. We analyzed genomic DNA from 169 patients with PBC and 225 geographically and sex-matched healthy subjects for polymorphisms of genes coding for cytochromes P450 (CYPs) 2D6 (CYP2D6*4, CYP2D6*3, CYP2D6*5, and CYP2D6*6) and 2E1 (c1/c2), multidrug resistance 1 (MDR1 C3435T) P-glycoprotein, and pregnane X receptor (PXR C-25385T, C8055T, and A7635G). We compared the genotype frequencies in patients and controls and also correlated polymorphisms with PBC severity. The distributions of the studied genotypes did not significantly differ between patients and controls. However, when clinical characteristics of patients with PBC were compared according to genotype, the CYP2E1 c2 allele was associated with signs of more severe disease . In conclusion, genetic polymorphisms of CYP 2D6 and 2E1, PXR, and MDR1 do not appear to play a role in the onset of PBC. (Hepatology 2005;41:55–63.)
Lymphedema; causes, complications and treatment of the swollen extremity.
Authors: William J. Grove
Journal: JAMA (1963)

The principal purpose of this brief monograph is to describe methods of surgical therapy of the chronically swollen extremity. The discussion is limited to consideration of swelling secondary to lymphatic derangement and does not deal with edema secondary to venous obstruction. However, the author does not clearly define the means by which the etiology of swelling can be determined. Perhaps in a volume of this type a discussion of differential diagnosis is not germane. Yet the author makes a strong plea that therapy should be based upon the determination of etiology. The chapters dealing with the anatomy and physiology of the lymphatic system, while brief, are adequate and up-to-date. The complications of chronic lymphedema, eg, lymphangiosarcoma, Kaposi's disease, are well described. Any one wishing to study the lymphatic system will find the section on lymphographic techniques useful. Yet, on the whole, the book contributes relatively little to the vexing problems
Comparative analyses of the prognostic value of novel cardiac markers in patients with non-ST elevation acute coronary syndromes
Authors: Oscar Bazzino, JoséL.Navarro Estrada, Fernando Botto, María I.Sosa Liprandi, Juan J. Fuselli, José Santopinto, Rodolfo Ahuad, Roberto Nordaby, Simón Salszberg, Alfredo Hirschson Prado, JoséGant López, Mario Russo, Fernando Sokn, Marcelo Pérez, Carlos Bruno
Journal: Journal of the American College of Cardiology (2002)
Include public interest defence in libel bill, say campaigners
Authors: C. Dyer
Journal: BMJ (2012)

Campaigners demanded a new public interest defence against libel claims in England and Wales and a ban on corporations suing for libel, in a rally at the UK parliament in London this week.

The Campaign for Libel Reform presented a petition with more than 60 000 signatures to 10 Downing Street calling for the measures to be included in the Defamation Bill, now going through parliament.

The campaign—made up of Sense About Science, English PEN, and Index on Censorship—persuaded all three main political parties that reform was needed to tackle the chilling effect of …
Removal of Iodized Oil After Myelography
Authors: Francis Schiller
Journal: JAMA (1964)

<h3>To the Editor:—</h3> After 35 years as a well-established diagnostic procedure, positive contrast myelography still arouses a certain uneasiness, and there is widespread fear of the medicolegal implications of the use of iodized oils in the spinal canal. In dogs, the intrathecal introduction of such oils appears to be regularly followed by the formation of adhesions around the cauda equina, with or without attendant progressive morbidity. Whether or not such adhesions occur in man in response to myelographic contrast media, or, if they do, whether they have morbid significance has not been established. Reports of chronic morbidity following myelography have been unconvincing. The very few deaths that have occurred immediately upon introduction of the oil are almost certainly attributable to idiosyncrasy. Aspiration of the oil, a painful procedure, is possibly harmful in itself. Whether a small residue is less damaging than a large one is not apparent; yet total removal
The Whistle in the Stomach, Who Blew It First? A Question of Priority
Authors: C. D. Spivak
Journal: JAMA (1910)

<h3>To the Editor:—</h3> The story is different from that told by Benjamin Franklin, but the moral is strikingly similar. Eleven or twelve years ago I was possessed by the ambition to devise a method by means of which the exact length of the esophagus migh be clinically determined. While waiting for inspiration I did the customary thing I whistled. Like Newton's discovery of the law of gravitation at seeing the apple fall, to me, likewise, came the idea while "wetting my whistle." Since my whistling at the esophagus and my whistling for the esophagus were like "whistling jigs to a milestone," why, thought I, whistling, not try to whistle into the esophagus? The result was that I did some more whistling and succeeded in hearing the sound of a whistle issuing from the innermost recesses of the abdominal viscera. To my ear it sounded like the first cry of my
RANDOMIZED CLINICAL TRIAL TO COMPARE THE NEPHROTOXIC EFFECTS OF ISO-OSMOLAR VS. LOW-OSMOLAR CONTRAST MEDIUM IN DIABETIC PATIENTS WITH REDUCED RENAL FUNCTION
Authors: Tobias Koppara, Rainer Wessely, Adnan Kastrati, Christian Bradaric, Stefanie Schulz, Marc Vorpahl, Siegmund Braun, Julinda Mehilli, Albert Schö;mig, Deutsches Herzzentrum München
Journal: Journal of the American College of Cardiology (2010)
Surprising Pleiotropy of Nerve Growth Factor in the Treatment of Experimental Autoimmune Encephalomyelitis
Authors: Richard M. Ransohoff, Corinna Trebst
Journal: The Journal of Experimental Medicine (2000)

The use of neurotrophic factors to treat multiple sclerosis (MS), a spontaneous inflammatory demyelinating disease of young adults, seems intuitively appealing: the process entails death of cellular constituents of the central nervous system (CNS), including oligodendroglia and neurons as well as
A NEW SPLINT FOR FRACTURED PATELLA
Authors: H. C. Masland
Journal: JAMA (1923)

Splints for the fractured patella have been generally unsatisfactory. The adhesive plaster used in making traction on the bones must pull on the skin and the soft tissue before it starts to draw on the bone. There is, in consequence, a redundancy, a wrinkling and compression of the soft tissues in the area between the broken fragments. The correct application of the splint here illustrated will give a direct grip and pull on the bones, while the superficial soft tissues can be drawn from under, both above and below the clutches. This gives a sufficiently taut superficial tissue covering the patella to prevent encroachment between the bones, which can be manipulated to coax out any synovial membrane that might be caught between them. As a preliminary, the splint should be trued. It can be placed on a table or other flat surface. The upright arms are placed vertical, and opposite
INTRAVENOUS UROGRAPHY IN THE DIAGNOSIS OF RUPTURE OF THE BLADDER
Authors: Ernest G. Mark
Journal: JAMA (1933)

The necessity for precise and early diagnosis in suspected rupture of the bladder is emphasized by practically all writers on the subject. In the gathered statistics of de Tarnowsky<sup>1</sup>it is quite definitely shown that when a diagnosis has been made and operative procedure instituted within the first twelve hours following injury, the mortality has been approximately 11 per cent. If such diagnosis and operative intervention are postponed into the twenty-four hour period, the mortality has risen to 55 per cent. The older method of diagnosing a ruptured bladder by the injection through a catheter of a known amount of fluid and the determination of the quantity of the returned fluid is open to the objection of the further diffusion of fluid through the bladder wound and the danger of infection. The method of Vaughan and Rudnick<sup>2</sup>of the injection of air by means of a catheter and
Potentiation of the contractile effects of norepinephrine by hypoxia
Authors: Kenneth M. Kent, Stephen E. Epstein, Theodore Cooper
Journal: Journal of Clinical Investigation (1972)

Hypoxia has been found to depress the concentration response curve of norepinephrine (NE) in isoalted cat papillary muscles. To investigate the effects of hypoxia in intact hearts, a heart-lung preparation was developed and maximum left ventricular dp/dt (max dp/dt) was measured at constant heart rate, preload, and after load. Left main coronary arterial flow (Qe) was measured with an electromagnetic flow probe. As arterial PO2 decreased from 90 mm Hg (96% saturation) to 20-25 mm Hg (40% saturation) at constant PCO2 and pH, no change in max dp/dt occurred and Qe increased 298%. In contrast to cat papillary muscles, the contractile responses to NE were augmented in hypoxia. The NE dose-response curves shifted to the left. No deterioration of contractility occurred after exposure to NE. In contrast, the chronotropic response was unaltered in hypoxia. Dose-response curves to isoproterenol also were shifted to the left in hypoxia, but responses to paired pacing were unchanged. The responses to NE under oxygenated conditions were unaltered by mechanically increased coronary flow or by increased coronary flow with nitroglycerin. Although the mechanisms responsible for these effects are unknown, the results suggest that hypoxia may open previously nonfunctioning vascular channels and thereby allow more extensive exposure of beta adrenergic receptors to circulating catecholamines.