tbuckley/cabot-search huggingface dataset:
Abstract 61: A new serotype chimera Cancer Terminator Virus (Ad.5/3-CTV) expands the efficiency and specificity of prostate cancer gene transfer and therapy
Authors: Belal Azab, Rupesh Dash, Swadesh Das, Sujit Bhutia, Xue-Ning Shen, Bridget Quinn, Santanu Dasgupta, Paul Dent, Igor Dmitriev, Xiang-Yang Wang, David Curiel, Steven Grant, Maurizio Pellecchia, John Reed, Devanand Sarkar, Paul Fisher
Journal: Cancer Research (2012)

Abstract Conditionally replication-competent adenoviruses (CRCAs) represent potentially useful reagents for treating prostate cancer (PC). We previously constructed a unique CRCA, Cancer Terminator Virus (CTV), in which the E1A gene, necessary for adenoviral replication, is controlled by the cancer-selective Progression Elevated Gene-3 (PEG-3) promoter and which simultaneously expresses melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) from the E3 region of the adenovirus. mda-7/IL-24, a novel member of the IL-10-related cytokine gene family, displays almost ubiquitous antitumor properties in vitro and in vivo, leading to its rapid entry into the clinic, where its safety and clinical efficacy, when administered by adenovirus (Ad.mda-7; INGN 241), was observed in a phase I clinical trial in humans with advanced carcinomas and melanomas. mda-7/IL-24 preferentially induces apoptosis in cancer cells while exerting no discernible toxic effects toward normal cells and it also elicits potent “antitumor bystander activity” in distant cancer cells as a consequence of autocrine and paracrine secretion of MDA-7/IL-24. The CTV was generated on a serotype 5 background (Ad.5-CTV) with infectivity depending on Coxsackie-Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective therapy. Using serotype chimerism, a novel CTV (Ad.5/3-CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber knob facilitating infection in a CAR-independent manner. We evaluated Ad.5/3-CTV in comparison with Ad.5-CTV in low CAR human PC cells, demonstrating higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3-CTV potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a spontaneously induced PC in Hi-myc transgenic mice. Ad.5/3.CTV exerted a marked anti-tumor ‘bystander’ effect in vivo confirming therapeutic utility. In these contexts, and considering the significant responses in a Phase I clinical trial of a non-replicating Ad.5-mda-7, the use of Ad.5/3-CTV to administer therapeutic and cytotoxic mda-7/IL24 to selectively induce cytolysis and apoptosis in prostate tumor cells represents a viable treatment options. (Supported by R01 CA097318 and P01 CA104177) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 61. doi:1538-7445.AM2012-61
Vasoactive intestinal peptide inhibitory innervation in bovine mesenteric lymphatics. A histochemical and pharmacological study.
Authors: T Ohhashi, J A Olschowka, D M Jacobowitz
Journal: Circulation Research (1983)

The localization of vasoactive intestinal peptide-immunoreactive nerves innervating bovine lymphatic vessels was studied by an immunohistochemical technique. Nerve fibers containing vasoactive intestinal peptide immunoreactivity were present in the smooth muscle layers as well as in the adventitia of all mesenteric lymphatics that were examined. The effect of vasoactive intestinal peptide on isolated lymphatic vessels in vitro was studied. Vasoactive intestinal peptide caused a concentration-dependent relaxation of bradykinin-induced contractions of lymphatic vessels. The threshold and maximum relaxations were achieved with vasoactive intestinal peptide at concentrations less than 6 X 10(-9) M and 3 X 10(-7) M, respectively. The relaxant response to vasoactive intestinal peptide was not modified by atropine, propranolol, bretylium, or tetrodotoxin. These results suggest that vasoactive intestinal peptide may be a possible inhibitory neurotransmitter that causes relaxation of lymphatic vessels.
Hemoglobin A1c Determinations in Diabetic Pregnancy
Authors: Hans Madsen, Jørn Ditzel, Peer Hansen, Niels Hahnemann, Ole Peter Andersen, Jens-Jørgen Kjaergaard
Journal: Diabetes Care (1981)

To investigate the relationship of hemoglobin A1c (HbA1c) to average blood glucose concentration and to birth weight of infants of diabetic mothers, HbA1c was determined in 42 consecutive insulin-dependent pregnant diabetic women in the third trimester. HbA1c correlated significantly to the average blood glucose levels in the preceding 8 wk (r = 0.73, P &amp;lt; 0.001). No correlation was found between HbA1c and the relative birth weight ratio (RBWR) for all newborn infants. However, in the major subgroups of pregnancies, White class B and C without prognostically bad signs in pregnancy (PBSP), HbA1c in the third trimester significantly correlated to RBWR (r = 0.59, P &amp;lt; 0.01). In a subgroup of six pregnant diabetic women in whom HbA1c and blood glucose concentrations frequently were determined from the 13th to the 33rd gestational week, a relationship between HbA1c and the average blood glucose concentration of the preceding 8 and 12 wk in the individual pregnant subject was established. In spite of this correlation, HbA1c was found to be a poor predictor of the average blood glucose concentration in the individual patient. This indicates that HbA1c cannot satisfactorily describe the degree of diabetes control without simultaneous determinations of blood glucose. HbA1c determinations were found to be of value as an additional indicator of the quality of regulation during ambulatory control in diabetic pregnancy because an increase in HbA1c suggested an impairment of diabetic control. The perinatal mortality and morbidity of the infants of diabetic mothers were satisfactory in this series, as only one perinatal death, one nonserious malformation, and two cases of mild respiratory distress syndrome occurred among the 43 infants.
RAS interaction with PI3K p110α is required for tumor-induced angiogenesis
Authors: Miguel Manuel Murillo, Santiago Zelenay, Emma Nye, Esther Castellano, Francois Lassailly, Gordon Stamp, Julian Downward
Journal: Journal of Clinical Investigation (2014)

Direct interaction of RAS with the PI3K p110α subunit mediates RAS-driven tumor development: however, it is not clear how p110α/RAS-dependant signaling mediates interactions between tumors and host tissues. Here, using a murine tumor cell transfer model, we demonstrated that disruption of the interaction between RAS and p110α within host tissue reduced tumor growth and tumor-induced angiogenesis, leading to improved survival of tumor-bearing mice, even when this interaction was intact in the transferred tumor. Furthermore, functional interaction of RAS with p110α in host tissue was required for efficient establishment and growth of metastatic tumors. Inhibition of RAS and p110α interaction prevented proper VEGF-A and FGF-2 signaling, which are required for efficient angiogenesis. Additionally, disruption of the RAS and p110α interaction altered the nature of tumor-associated macrophages, inducing expression of markers typical for macrophage populations with reduced tumor-promoting capacity. Together, these results indicate that a functional RAS interaction with PI3K p110α in host tissue is required for the establishment of a growth-permissive environment for the tumor, particularly for tumor-induced angiogenesis. Targeting the interaction of RAS with PI3K has the potential to impair tumor formation by altering the tumor-host relationship, in addition to previously described tumor cell-autonomous effects.
Sequence variant on 8q24 confers susceptibility to urinary bladder cancer
Authors: Lambertus A Kiemeney, Steinunn Thorlacius, Patrick Sulem, Frank Geller, Katja K H Aben, Simon N Stacey, Julius Gudmundsson, Margret Jakobsdottir, Jon T Bergthorsson, Asgeir Sigurdsson, Thorarinn Blondal, J Alfred Witjes, Sita H Vermeulen, Christina A Hulsbergen-van de Kaa, Dorine W Swinkels, Martine Ploeg, Erik B Cornel, Henk Vergunst, Thorgeir E Thorgeirsson, Daniel Gudbjartsson, Sigurjon A Gudjonsson, Gudmar Thorleifsson, Kari T Kristinsson, Magali Mouy, Steinunn Snorradottir, Donatella Placidi, Marcello Campagna, Cecilia Arici, Kvetoslava Koppova, Eugene Gurzau, Peter Rudnai, Eliane Kellen, Silvia Polidoro, Simonetta Guarrera, Carlotta Sacerdote, Manuel Sanchez, Berta Saez, Gabriel Valdivia, Charlotta Ryk, Petra de Verdier, Annika Lindblom, Klaus Golka, D Timothy Bishop, Margaret A Knowles, Sigfus Nikulasson, Vigdis Petursdottir, Eirikur Jonsson, Gudmundur Geirsson, Baldvin Kristjansson, Jose I Mayordomo, Gunnar Steineck, Stefano Porru, Frank Buntinx, Maurice P Zeegers, Tony Fletcher, Rajiv Kumar, Giuseppe Matullo, Paolo Vineis, Anne E Kiltie, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Thorunn Rafnar, Kari Stefansson
Journal: Nature Genetics (2008)
Asian Influenza (1957) in Allergic Patients
Authors: B. Bendkowski
Journal: BMJ (1958)

DICAL IOAL isolated from the brain so far, and its significance cannot therefore be assessed without further study.This is being carried out in the Pathology Department of the Armed Forces Medical College, India.It is difficult to state whether the neurological and hepatic syndromes were caused by a new mutant of influenza virus, by the activation during the influenza epidemic of an associated neuro-viscerotrophic virus, or by a hybridization of viruses of the type produced by Burnet (1957) in his experimental genetic studies on viruses. SummaryA short account of the origin and spread of the pan- demic of influenza of 1957 is given.In India cases started appearing in Madras in M1ay, 1957, and very soon after it spread to the rest of South India.Out of a total of 9,459 cases of influenza admitted to military hospitals in South India, 30 developed manifestations of neurological and hepatic involvement.Sixteen of these were reported from one station in 17 days and five from another in 27 days.
A CRITICISM OF THE BLOOD-PRESSURE APPARATUS
Authors: C. F. HOOVER
Journal: JAMA (1910)

The sphygmomanometer is generally assumed to be an instrument which enables us to measure the maximum and minimum endovascular arterial pressure. If this assumption is true, it does not follow that we have any data on which to estimate the mass movement of blood, the real problem that remains to be solved in the study of cardiovascular diseases. In subjects with a normal vascular system the blood-pressure apparatus gives us reliableinformation about the maximum systolic pressure. But in clinical experience it can be shown that the blood-pressure apparatus gives misleading information even on this basic point. The diastolic blood-pressure can be measured about as accurately as the systolic blood-pressure. But the diastolic endovascular pressure is not a measure of the systole of an artery. In other words, we may have the equivalent of a normal diastolic pressure and the artery remain full of blood during the cardiac diastole. We are perfectly famtiliar with
Paediatric drug development: The impact of evolving regulations
Authors: M.A. Turner, M. Catapano, S. Hirschfeld, C. Giaquinto
Journal: Advanced Drug Delivery Reviews (2014)

Children deserve medicines that are adapted to their needs. The need to include children in drug development has been recognised increasingly over the past few decades. Legal and regulatory frameworks are well established in the EU and US. The amount of work done to study medicines for children is significantly greater than it was 10 years go. Proof-of-concept has been demonstrated for all segments of the paediatric drug development pipeline. It is now time to examine how the practice of developing medicines for children has evolved within those frameworks and to determine how that work should be generalised. This review describes the development of medicines for children and critically appraises the work that has been done within those frameworks. Significant effort is needed to realize the potential provided by the current regulatory framework. Using the work programme of the Global Research in Paediatrics (GRiP) Network of Excellence as a template we outline current work and future growing points.
Better sex education for children is needed to combat dangers of pornography
Authors: I. Laws
Journal: BMJ (2013)

It should be mandatory for schools to provide supportive health education to children to reduce teenagers’ use of pornography and the subsequent risks to health of such exposure, public health experts have said.

Speakers told a media briefing at the Wellcome Trust in London on 19 September that boys and girls could become drawn to pornography if their questions about sex and relationships were not answered in the classroom. 

A report commissioned …
The effect of co-culturing costal chondrocytes and dental pulp stem cells combined with exogenous FGF9 protein on chondrogenesis and ossification in engineered cartilage
Authors: Jiewen Dai, Jia Wang, Jingting Lu, Duohong Zou, Hao Sun, Yuefu Dong, Hongbo Yu, Lei Zhang, Tong Yang, Xiuli Zhang, Xudong Wang, Guofang Shen
Journal: Biomaterials (2012)
Primary sclerosing cholangitis: Summary of a workshop
Authors: Nicholas F. LaRusso, Benjamin L. Shneider, Dennis Black, Gregory J. Gores, Stephen P. James, Edward Doo, Jay H. Hoofnagle
Journal: Hepatology (2006)

Primary sclerosing cholangitis (PSC) is a rare but important liver disease that leads to cirrhosis and need for liver transplantation in a high proportion of cases. The disease occurs in approximately 1 per 100,000 population per year, usually presents in adulthood, and affects men more often than women. Typical serum biochemical results, autoantibodies and liver biopsy are suggestive but not diagnostic of PSC, the diagnosis requiring cholangiographic demonstration of stricturing and dilatation of the intra- and/or extra-hepatic bile ducts. The natural history of PSC is variable, the average survival being 12 to 17 years. The cause of PSC is still unknown. Although considered an autoimmune disease, PSC has several atypical features and a strong genetic component. The therapy of PSC is unsatisfactory. Standard doses of ursodeoxycholic acid (UDCA) lead to improvements in biochemical abnormalities but not in histology, cholangiographic appearance or survival. Several innovative therapies have been tried in PSC, but with scant evidence of benefit. For patients with high grade strictures, endoscopic dilatation is beneficial. Liver transplantation is successful for end-stage liver disease due to PSC and improves survival. PSC may recur after transplantation but is rarely progressive. The most dreaded complication of PSC is cholangiocarcinoma. Diagnosis of this highly malignant tumor is difficult, and there are no biomarkers for its early detection. Liver transplantation for cholangiocarcinoma has an exceedingly poor outcome, although transplantation with neoadjuvant chemoirradiation holds promise in selected patients. Thus, significant opportunities remain for basic and clinical research into the cause, natural history, and therapy of PSC.
Move to sell statins over the counter raises concerns
Authors: Liza Gibson
Journal: BMJ (2004)

Doctors' leaders and consumer bodies have raised concerns about the UK government's decision to allow the cholesterol lowering agent, simvastatin, to become available without prescription in pharmacies.

The reclassification, announced last week by the Department of Health to increase patients' choice and to help reduce coronary heart disease, will be the world's first for a statin. About 1.8 million people in England are prescribed statins, costing the NHS around £700m ($1200m; €1000m) a year. Some £309m is spent on simvastatin alone.

The over the counter product, to be called Zocor Heart-Pro (10 mg), will be aimed at …
Obesity Does Not Modulate Insulin Secretion in Indian Patients with Non-insulin-dependent Diabetes in the Young
Authors: I Jialal, S M Joubert
Journal: Diabetes Care (1984)

The insulin response to a 100-g oral glucose load was studied in 40 obese (percent desirable weight ≥ 120%) and 40 nonobese (&amp;lt; 120%) age- and sex-matched Indian patients with non-insulin-dependent diabetes in the young. There were no significant differences between the obese and nonobese patients with respect to their insulin and glucose responses. Thus, it appears that obesity does not exert a significant modulating effect on insulin secretion in patients with fasting hyperglycemia.
Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.
Authors: G C Hard, I S Rodgers, K P Baetcke, W L Richards, R E McGaughy, L R Valcovic
Journal: Environmental Health Perspectives (1993)

This review paper examines the relationship between chemicals inducing excessive accumulation of alpha 2u-globulin (alpha 2u-g) (CIGA) in hyaline droplets in male rat kidneys and the subsequent development of nephrotoxicity and renal tubule neoplasia in the male rat. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens from classical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity, CIGA or their metabolites bind specifically, but reversibly, to male rat alpha 2u-g. The resulting complex appears to be more resistant to hydrolytic degradation in the proximal tubule than native, unbound alpha 2u-g. Single cell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell proliferation, foci of tubule hyperplasia in the convoluted proximal tubules, and renal tubule tumors. Although structurally similar proteins have been detected in other species, including humans, renal lesions characteristic of alpha 2u-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an alpha 2u-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development of renal tubule tumors in male rats. Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing alpha 2u-g accumulation are unlikely to occur in humans.
PRENATAL RUPTURE OF THE INTESTINE WITH SUBSEQUENT DYSTOCIA
Authors: James Hubert Skiles
Journal: JAMA (1928)

Prenatal rupture of the intestine is a rare condition and only a few cases have been described in the literature. Its rarity would seem a sufficient excuse for reporting a case aside from several interesting features connected with it. A search of the literature has been made and nothing has been discovered in English. The German literature reveals a few cases of prenatal rupture of the intestine. The earliest description of a case found was that of Breslau<sup>1</sup>in 1863. A baby girl with breech presentation died during instrumental delivery. An autopsy revealed perforations at the transition of the ascending colon to the transverse colon. The author believed that the perforations occurred before birth. There was evidence of peritonitis with meconium adhesions and fresh exudative general peritonitis in the abdomen but without gas. In 1891, Genersich<sup>2</sup>reported a case in which the child died
Prevention of hyperglycemia in Zucker diabetic fatty rats by exercise training: effects on gene expression in insulin-sensitive tissues determined by high-density oligonucleotide microarray analysis
Authors: Michele Colombo, Soeren Gregersen, Mogens Kruhoeffer, Andreas Agger, Jianzhong Xiao, Per Bendix Jeppesen, Torben Orntoft, Thorkil Ploug, Henrik Galbo, Kjeld Hermansen
Journal: Metabolism (2005)
The 2.5 Å Structure of CD1c in Complex with a Mycobacterial Lipid Reveals an Open Groove Ideally Suited for Diverse Antigen Presentation
Authors: Louise Scharf, Nan-Sheng Li, Andrew J. Hawk, Diana Garzón, Tejia Zhang, Lisa M. Fox, Allison R. Kazen, Sneha Shah, Esmael J. Haddadian, Jenny E. Gumperz, Alan Saghatelian, José D. Faraldo-Gómez, Stephen C. Meredith, Joseph A. Piccirilli, Erin J. Adams
Journal: Immunity (2010)
Insulin-like growth factor and growth hormone secretion in juvenile chronic arthritis.
Authors: R C Allen, M Jimenez, C T Cowell
Journal: Annals of the Rheumatic Diseases (1991)

Insulin-like growth factor (IGF-1) concentrations were determined in a series of 23 children with juvenile chronic arthritis in conjunction with anthropometric assessment. When standardised z scores were used significant decreases in height and weight were shown in comparison with the normal age/sex matched means. Severe growth disturbance was seen, particularly in those with prolonged disease duration, which was independent of corticosteroid treatment, indicating disease activity itself is a major factor in the growth retardation. Eight children had low IGF-1 z scores--that is, less than -2.00 from age/sex matched mean. Low IGF-1 z scores were associated with low weight z scores but not with low height z scores. Overnight growth hormone secretory profiles were determined in 10 patients, including seven with low IGF-1, and showed generally normal secretion in all but one patient, who subsequently attained normal concentrations coincident with catch up growth. Increased pulse frequency of overnight secretion was commonly seen. Low IGF-1 concentrations probably result from varying factors, particularly nutritional, but do not reflect marked endocrinological abnormalities in most patients.
Human In Vitro Fertilization
Authors: Hans O. Tiefel
Journal: JAMA (1982)

Ethical objections to both the means and ends of clinical in vitro fertilization and embryo transfer, as well as of nonclinical applications, are analyzed and evaluated. Morally important but inconclusive arguments consider these procedures to be unnatural or harmful to women. The decisive objection to clinical uses lies in the possible and even likely risk of greater than normal harm to offspring. A discussion of the need and right to have children, and of the relationship of this procedure to abortion and to freezing embryos, concludes the analysis of clinical uses. The ethics of research applications of in vitro fertilization hinges on the status of the embryo. After prefatory conceptual clarification, this article argues for the inclusion of human embryos within protectable humanity, which makes nontherapeutic research unjustifiable. Public decision making and federal research funding are discussed. (<i>JAMA</i>1982;247:3235-3242)
Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium.
Authors: M Yamada, T Ohkusa, I Okayasu
Journal: Gut (1992)

In this study, long term dextran sulphate sodium administration was studied to ascertain whether colorectal carcinoma could be produced in patients with long standing ulcerative colitis. Simultaneously, changes in the intestinal microflora were analysed. Low grade to high grade dysplasia was seen in three of the five hamsters treated with 1% dextran sulphate sodium solution for 100 days, while no dysplasia was detected in the eight animals concomitantly treated with metronidazole, an antianerobic microbial agent, which prevents colonic ulceration. In these two groups, none of the animals developed colorectal cancer over 100 day period. In a group treated for 180 days, seven of the eight animals had dysplasia, and one had two adenomas. Furthermore, four of the eight animals had adenocarcinoma in the transverse colon; they were protruding well differentiated adenocarcinoma in one and non-protruding lesions infiltrating into the musclaris propria in three. The three non-protruding infiltrating adenocarcinomas were classified to be well differentiated adenocarcinoma in one and mucinous adenocarcinoma in two, resembling the type of cancer which complicates ulcerative colitis in man.